Abstract
Background
This study aimed to investigate the clinical, serological and myopathological features of Chinese patients with inclusion body myositis (IBM).
Methods
This study retrospectively recruited patients diagnosed with IBM according to the 2024 European Neuromuscular Center (ENMC) criteria at Peking University First Hospital between 2004 and 2024. Clinical features, pathological changes and laboratory data were collected. Subgroups were analyzed by sex, dysphagia, anti-cN1A antibody status, and complement deposition.
Results
Forty-three IBM patients (25 males) were included in this cohort. The mean age at onset was 54.9 ± 9.6 years old. All the patients developed weakness in hip flexion, and 81.4% of them with weakness in both knee extension and finger flexion. Dysphagia was reported in 17 patients (39.5%). Endomysial inflammation was observed in all the patients, and 79.1% with rimmed vacuoles, and 76.9% with mitochondrial abnormalities. Female patients more frequently developed dysphagia (P = 0.005) and neck flexion weakness (P < 0.001). Anti-cN1A antibody was positive in 20 patients (66.7%). Seropositive cases were associated with a later age of onset (P = 0.034). Complement deposition was observed in 77.4% of patients and was associated with more severe muscle weakness.
Conclusion
This cohort of Chinese IBM patients suggested an earlier age at onset than previously reported. Hip flexors were most commonly affected. Female patients showed a higher frequency of dysphagia and neck flexor weakness. Our study reported a high frequency of complement deposition in muscle tissue. Complement deposition was associated with disease severity, suggesting a potential role of complement in the pathophysiology of IBM.
Keywords: anti-cN1A antibody, complement deposition, dysphagia, IBM, inclusion body myositis
Introduction
Inclusion body myositis (IBM) is the most common inflammatory myopathy in Caucasian patients aged over 50 years, characterized by slowly progressive muscle weakness, predominantly in the flexor digitorum profundus and quadriceps femoris (1). The diagnosis of IBM relies on both clinical and pathological features. The 2024 revised European Neuromuscular Center (ENMC) diagnostic criteria specifies endomysial lymphocytes surrounding non-necrotic muscle fibers (with or without invasion) as mandatory myopathological feature, and rimmed vacuoles and/or cytoplasmic protein aggregates and mitochondrial abnormalities as supportive features (2). Due to the heterogeneity of clinical and pathological findings, IBM is frequently misdiagnosed at initial clinic visit. The 2024 ENMC criteria for the first time incorporated atypical presentations, including early-onset disease, axial weakness, isolated dysphagia, foot drop, facial diplegia and proximal limb weakness (2). The etiology of IBM remains elusive (3, 4), and it is refractory to conventional immunotherapy, often leading to significant functional decline in daily activities among elderly patients (5).
Over the past decade, the serum anti-cytosolic 5’-nucleotidase 1A (cN1A) antibody has emerged as a potential biomarker for IBM (6). However, its reported sensitivity varies ranging from 37% in European cohorts to approximately 60% in North American studies and up to 80% in Japanese patients (7–9). In addition, anti-cN1A antibodies are not specific to IBM and can also be detected in other idiopathic inflammatory myopathies, Sjögren’s syndrome, and systemic lupus erythematosus (8, 10). It has remained under debate whether the clinicopathological features were different between seropositive and seronegative IBM patients. Some studies reported that seropositive patients present with more severe motor or bulbar involvement (11, 12). Some studies described fewer rimmed vacuoles or a higher burden of cytochrome c oxidase (COX)-deficient fibers in seropositive cases (7, 8), whilst others found no significant clinicopathological differences between seropositive and seronegative cases (13–15).
IBM has been rarely reported in China, mostly described in case reports and small cohorts (16, 17). In a study of 28 Chinese patients, quadriceps were the most commonly affected, while conspicuous muscle atrophy in quadriceps was observed in only 17.9% (16). In addition, the anti-cN1A antibody has never been systematically studied in Chinese patients. This highlights the need for comprehensive clinical and pathological profiling of IBM in Chinese population.
Therefore, this study aimed to characterize the clinical, serological and myopathological features of Chinese patients with IBM.
Materials and methods
Patients
Medical records and muscle histopathology were retrospectively reviewed for the patients who were diagnosed as “IBM” or “possible IBM” at Peking University First Hospital (PKUFH) between 2004 and 2024. The patients fulfilling the 2024 ENMC criteria for IBM were recruited to this study (2). Clinical information included the following items: age at onset, sex, disease duration, age at biopsy, diagnostic interval, past medical history, symptoms at onset, muscle weakness distribution, comorbidities, serum creatine kinase (CK) level, and serum anti-cN1A antibody status. In this study, age at onset referred to the date when symptoms of IBM were reported by the patient. Disease duration was defined as the time from disease onset to the time of assessment. Diagnostic interval referred to the time from onset to the diagnosis.
Manual muscle strength was recorded in 13 muscle groups using the Medical Research Council (MRC) scale, including neck flexors, shoulder abductors, elbow flexors and extensors, wrist flexors and extensors, finger flexors and extensors, hip flexors, knee flexors and extensors, ankle dorsiflexors and plantar flexors (18, 19). MRC grades were further converted to a 10-point Kendall scale for analysis according to the previous studies (19, 20). The conversion criteria were provided in Supplementary Table 1. Muscle strength of each muscle group was calculated as the average of both sides of the limbs. Muscle strength sum score (SSS) was the total score of all the muscle groups, ranging from 0 (complete paralysis of the included muscles) to 130 (normal). IBM functional rating scale (IBMFRS) scores were assessed during the physical examination. All clinical assessments were performed by two neuromuscular specialists at PKUFH.
Serum anti-cN1A antibody was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (EUROIMMUN, Lübeck, Germany), or commercial cell-based assay (CBA) method (KingMed Diagnostics, Guangzhou, China). The choice of method for antibody testing depended on which method was available at the time of evaluation.
Muscle biopsy
The muscle biopsies from our center were reviewed and analyzed by two neuropathologists. Histochemistry stainings included hematoxylin and eosin (H&E), modified Gömöri trichrome (mGT) and cytochrome c oxidase/succinate dehydrogenase (COX/SDH) staining. Immunohistochemistry stainings were performed using antibodies against the following antigens: major histocompatibility complex class I (MHC-I), CD3, CD4, CD8, CD20, CD68, C5b-9, p62 and TDP-43. The available electron microscopy (EM) slides were also thoroughly reviewed. Histopathological features were recorded, including perimysial inflammation, endomysial inflammation, endomysial fibrosis, inflammatory invasion or infiltration of non-necrotic muscle fibers, rimmed vacuoles (RVs), MHC-I, mitochondrial abnormalities, complement deposition and p62 protein aggregates on light microscopy, and tubulofilamentous inclusions on the EM. In this study, mitochondrial abnormalities were defined as the presence of at least one of the following features: COX-negative fibers, ragged-red fibers (RRF), or ragged-blue fibers (RBF).
Histopathological features were further analyzed for the patients who had a biopsy in our center and also tested for anti-cN1A antibody. The degree of inflammatory cells was scored according to Pinto et al. on a scale from 0 (absence), 1 (minimal scattered inflammation), 2 (1 small collection per 5×field), 3 (2 small collections per 5×field), to 4 (3 or more small collections per 5×field) (21). C5b-9 staining was scored according to Yang et al. on a scale from 0 (absence), 1 (<3% of muscle fibers in whole biopsy), 2 (3–10% of muscle fibers in whole biopsy), 3 (11–30% of muscle fibers in whole biopsy), to 4 (>30% of muscle fibers in whole biopsy) (22). MHC-I staining was scored according to Lindvall et al. on a scale from 0 (negative on muscle fibers), 1 (expression on parts of the muscle fiber membrane in parts of the muscle biopsy), 2 (expression on parts of the muscle fiber membrane throughout the biopsy), 3 (expression involving the total of the muscle fiber membrane), 4 (3 with addition groups of dark, granulated muscle fibers) to 5 (3 with granulated muscle fibers present throughout the biopsy) (23). The amount of COX-negative fibers and p62 deposition were scored semi-quantitatively according to Pinto et al. on a scale from 0 (absence), 1 (≤3 of muscle fibers in whole biopsy), 2 (>3 of muscle fibers in the whole biopsy, and 0–1 muscle fiber in a 10× field), 3 (1–2 of muscle fibers in a 10×field), to 4 (≥2 of muscle fibers in a 10×field) (21).
Statistical analysis
Continuous variables that followed a normal distribution were summarized as mean ± standard deviation, and continuous variables that were not normally distributed were presented as median (interquartile range, IQR). Categorical variables were summarized as counts (percentages). The cohort was stratified according to several clinically relevant aspects, including sex, age at onset, dysphagia, anti-cN1A antibody status, and complement deposition. Age at onset was categorized as <50 years group and ≥50 years group. Complement deposition was classified as score >2 group and score ≤2 group. Subgroup comparisons were assessed by using the independent samples t-test or the Mann-Whitney U test for continuous variables, and the Chi-square test for categorical variables.
Further validation was performed for outcomes in unadjusted analyses by using analysis of covariance (ANCOVA) for continuous outcomes and binary logistic regression for categorical outcomes. Adjustment analyses were performed for predefined relevant covariates, including sex, age at onset, disease duration and age at biopsy. A p-value of less than 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics 27.
Results
Demographics and clinical findings
This retrospective study identified 43 IBM patients fulfilling the 2024 ENMC criteria between January 2004 and May 2024. Thirty-six patients performed muscle biopsy in our center. The total number of muscle biopsies for patients aged over 18 years old was 6,535 during this period, and the proportion of IBM was 0.55% (36/6,535) in our center. (Table 1). Twenty-five (58.1%) were males, with a male-to-female ratio of 1.4:1. The mean age at onset was 54.9 ± 9.6 years (ranged from 30 to 78 years). Five patients (11.6%) presented with their first symptoms before the age of 45. The median diagnostic interval was 5 years (IQR 3 to 6 years). The most common symptom at onset was weakness in bilateral proximal lower limbs (n = 32, 74.4%). Three patients (7.0%) presented with weakness in both upper and lower limbs, and two patients (4.7%) presented with proximal upper limb weakness. Two patients (4.7%) presented with dysphagia as the first symptom. At the time of clinical assessment, all the patients developed weakness in hip flexion, 38 patients (88.4%) presented weakness in knee extension, and 40 patients (93.0%) presented with weakness in finger flexion. (Table 1). Notably, the strength of knee extension was weaker than hip flexion in the majority of the patients (n = 29, 67.4%). Thirty-five patients (81.4%) presented with the typical clinical features of weakness in both knee extension and finger flexion, and muscular atrophy in the bilateral thighs and forearms was shown in Figure 1. In addition, 30 patients (69.8%) developed weakness in neck flexion, and 17 patients (39.5%) developed dysphagia. (Table 1 and Supplementary Table 2).
Table 1.
Clinical characteristics of the overall cohort and comparisons by sex.
| Characteristics | Total | Sex group | ||
|---|---|---|---|---|
| Female | Male | P | ||
| Demographics, n=43 | ||||
| Female (%) | 18/43(41.9) | — | — | — |
| Age at onset, yrs | 54.9 ± 9.6 | 54.4 ± 10.7 | 55.2 ± 8.9 | 0.767 |
| Disease Duration, yrs | 5.0 (3.0,6.0) | 4.5(3,7) | 5(3,7) | 0.765 |
| Age at biopsy, yrs | 60.1 ± 9.5 | 60.2 ± 10.5 | 60.1 ± 9.0 | >0.999 |
| Clinical feature, n =43 | ||||
| KE weakness (%) | 38/43(88.4) | 17/18(94.4) | 21/25(84) | 0.292 |
| HF weakness (%) | 43/43(100) | 18/18(100) | 25/25(100) | — |
| KE ≤ HF (%) | 33/43(76.7) | 12/18(66.7) | 21/25(84) | 0.275 |
| FF weakness (%) | 40/43(93.0) | 18/18(100) | 22/25(88) | 0.128 |
| NF weakness (%) | 30/43(69.8) | 18/18(100) | 12/25(48) | <0.001* |
| Strength sum scores | 99.6 (87.5,108.5) |
97.05 (85.675,105.675) |
102.5 (87.75,109.4) |
0.362 |
| Upper limb muscle strength | 59.0(52.0,64.9) | 55.8(51.45,65.275) | 61.9(53.164.8) | 0.284 |
| Lower limb muscle strength | 42.0(36.0,45.0) | 41.75(36,44) | 42.5(34.25,46.25) | 0.579 |
| Dysphagia (%) | 17/43(39.5) | 12/18(66.7) | 5/25(20) | 0.002** |
| IBMFRS scores | 33(29,37) | 32.5(28.75,35.5) | 33(29,37.5) | 0.666 |
| CK, IU/L | 865(401,1200) | 780.5(338.25,1345) | 908(405.5,1403) | 0.530 |
| Muscle biopsy feature | ||||
| Endomysial inflammation (%), n=43 | 43/43(100) | 18/18(100) | 25/25(100) | — |
| Perimysial inflammation (%), n =43 | 11/43(25.6) | 7/18(38.9) | 4/25(16) | 0.090 |
| Invasion or surrounding of non-necrotic muscle fibers (%), n=43 | 38/43(88.4) | 16/18(88.9) | 22/25(88) | 0.929 |
| RV (%), n=43 | 34/43(79.1) | 11/18(61.1) | 23/25(92) | 0.014*** |
| MHC-I positivity (%), n=36 | 36/36(100) | 15/15(100) | 21/21(100) | — |
| Mitochondrial abnormalities (%), n=39 | 30/39(76.9) | 13/15(86.7) | 17/24(70.8) | 0.437 |
| Endomysial fibrosis (%), n=37 | 28/37(75.7) | 12/15(80) | 16/22(72.7) | 0.711 |
| Complement positive (%), n=31 | 24/31(77.4) | 9/11(81.8) | 15/20(75) | >0.999 |
| p62 deposition (%), n=27 | 25/27(92.3) | 9/10(90) | 16/17(94.1) | 0.760 |
Data were presented as median (IQR) or n/N (%) (N represented data available for analysis per variable); yrs = years; KE, knee extension; HF, hip flexion; FF, finger flexion; NF, neck flexion; IBMFRS, inclusion body myositis functional rating scale; CK, creatine kinase; RV, rimmed vacuoles; MHC, major histocompatibility.
*Only unadjusted analysis was performed due to complete separation arising from a 100% event rate in this subgroup.
**Adjusted for disease duration and age at onset, P = 0.005, OR = 8.57, 95% CI 1.95 to 37.73.
***Adjusted for age at onset and age at biopsy, P = 0.027, OR = 0.14, 95% CI 0.02 to 0.79.
Bold values indicate statistically significant results with a P-value < 0.05.
Figure 1.
Typical distribution of muscle atrophy in a patient with IBM. (A) Muscle atrophy in the bilateral quadriceps muscles. (B) Muscle atrophy in the bilateral forearms and weakness in hand grip and finger flexion.
IBMFRS was evaluated in 39 patients with a median score of 33 (IQR 29–37). Serum CK levels were within normal range (≤170 IU/L) in 24 patients (55.8%). Two patients (4.7%) showed a marked elevation of CK level over 15 times of the upper limit of normal (>2550 IU/L). The overall median CK level was 865 IU/L (range from 38 to 4000). As for comorbidities, seven patients (16.3%) had Sjögren’s syndrome (SS), four patients (7.0%) had possible SS or undifferentiated connective tissue disease, 12 patients (27.9%) had coronary heart disease, 18 patients (41.9%) had hypertension, 12 patients (27.9%) had diabetes mellitus, one patient (2.3%) had chronic hepatitis B virus (HBV) infection, one patient (2.3%) had chronic hepatitis C virus (HCV) infection, and one patient (2.3%) had monoclonal gammopathy of undetermined significance (MGUS). (Table 1 and Supplementary Table 2).
None of the patients reported a family history of neuromuscular diseases or genetic disorder. Whole-exome sequencing (WES) was performed in 23 patients, and a variant in the SQSTM1 gene was identified in one patient (unpublished data).
Muscle biopsy findings
All the patients had a muscle biopsy, mostly in the quadriceps femoris (n = 22, 51.2%) and biceps brachii (n = 19, 44.2%), and only one in the tibialis anterior and gastrocnemius muscles, respectively. Thirty-eight patients were performed muscle biopsies in our center. (Table 1 and Supplementary Table 2). Endomysial inflammatory infiltrates were observed in all the patients, and lymphocytes invasion or surrounding of non-necrotic muscle fibers was seen in 38 (88.4%) of them. (Figure 2A). Rimmed vacuoles and mitochondrial abnormalities were found in 34 patients (79.1%) and 30 patients (76.9%), respectively. (Figures 2B, C). Immunohistochemistry stainings showed up-regulation of MHC-I expression in all the patients, and CD8-positive T-cell infiltration in 30 patients (93.8%). (Figures 2D, E) Complement deposition on the sarcolemma of non-necrotic muscle fibers was observed in 24 patients (77.4%). (Figure 2F). In addition, perimysitis and perivascular inflammation were also observed in 11 patients (25.6%) and 15 patients (34.9%), respectively. P62 staining was performed in 27 patients, and p62 protein aggregations were observed in 25 of them (92.6%). (Figure 2G). TDP-43 staining was performed in 14 patients, and TDP-43 mislocalization was observed in 12 patients (85.7%). (Figure 2H). EM was performed in 23 patients, and tubulofilamentous inclusions were found in 15 patients (65.2%). (Figure 2I).
Figure 2.
Muscle biopsy in vastus lateralis of a patient with IBM. (A) H&E staining showed endomysial inflammatory cells invasion and surrounding non-necrotic muscle fibers. (B) mGT staining confirmed the presence of RVs (arrow). (C) COX/SDH staining showed multiple COX-negative fibers (arrow). (D) Diffuse MHC-I up-regulation in the sarcolemma and cytoplasm of muscle fibers. (E) CD8 immunohistochemistry revealed cytotoxic T-cells infiltration. (F) C5b-9 staining showed complement deposition on the sarcolemma of non-necrotic fibers. (G) p62 protein aggregates within fibers (arrow). (H) TDP-43 mislocalization to the cytoplasmic of muscle fibers (arrow). (I) The tubulofilamentous inclusions were confirmed by EM (arrow). Scale bars were 50 μm in (A, C-F), 20 μm in (B, G, H), and 500 nm in (I) .
Correlation analysis
Comparisons between age-at-onset groups showed no significant differences in either clinical or pathological features. (Supplementary Table 3). The differences between sex were also analyzed. (Table 1). After adjustment for disease duration and age at onset, dysphagia was more frequent in females than the males (P = 0.005). Neck flexor weakness was present in all the females compared with 48% of males, with statistically significant difference (P < 0.001). Histopathological findings showed that female patients had a significantly lower frequency of RVs in muscle biopsies (P = 0.027).
Patients were stratified by the presence or absence of dysphagia for comparative analysis. (Table 2 and Supplementary Table 4). The initial unadjusted analysis indicated that dysphagia was associated with weakness in neck flexion and upper limb muscle strength, particularly in wrist flexion. However, these differences were no longer statistically significant after adjustment for age at onset, disease duration, and sex.
Table 2.
Comparison of clinical and pathological characteristics between the subgroups of dysphagia.
| Characteristics | with dysphagia | without dysphagia | P |
|---|---|---|---|
| Demographics, n = 43 | |||
| Female (%) | 12/17(70.6) | 6/26(23.1) | 0.002* |
| Age at onset, yrs | 52.9 ± 8.8 | 56.1 ± 10.0 | 0.390 |
| Disease Duration, yrs | 5(3,10) | 4(3,5.25) | 0.196 |
| Age at biopsy, yrs | 59.4 ± 8.4 | 60.6 ± 10.4 | 0.718 |
| Clinical feature, n = 43 | |||
| KE weakness (%) | 16/17(94.1) | 22/26(84.6) | 0.342 |
| HF weakness (%) | 17/17(100) | 26/26(100) | — |
| KE ≤ HF (%) | 12/17(70.6) | 21/26(80.8) | 0.440 |
| FF weakness (%) | 16/17(94.1) | 24/26(92.3) | 0.820 |
| NF weakness (%) | 16/17(94.1) | 14/26(53.8) | 0.005** |
| Strength sum scores | 92.6(83.5,104.4) | 102.95(91,109.85) | 0.112 |
| Upper limb muscle strength | 54.2(50.45,61.15) | 61.95(55.75,66) | 0.047*** |
| Lower limb muscle strength | 41.5(34.5,44) | 42.5(36,45.25) | 0.551 |
| IBMFRS scores | 32(29,36.5) | 33.5(29.75,38.25) | 0.575 |
| CK, IU/L | 860(38,3538) | 920.5(399,1301.5) | 0.990 |
| Muscle biopsy feature | |||
| Endomysial inflammation (%), n=43 | 17/17(100) | 26/26(100) | — |
| Perimysial inflammation (%), n =43 | 6/17(35.3) | 5/26(19.2) | 0.238 |
| Invasion or surrounding of non-necrotic muscle fibers (%), n=43 | 14/17(82.4) | 24/26(92.3) | 0.319 |
| RV (%), n=43 | 12/17(70.6) | 22/26(84.6) | 0.269 |
| MHC-I positivity (%), n=36 | 16/16(100) | 20/20(100) | — |
| Mitochondrial abnormalities (%), n=39 | 12/15(80) | 18/24(75) | >0.999 |
| Endomysial fibrosis (%), n=37 | 11/15(73.3) | 17/22(77.3) | >0.999 |
| Complement positive (%), n=31 | 10/13(76.9) | 14/18(77.8) | >0.999 |
| P62 deposition (%), n=27 | 7/8(87.5) | 18/19(94.7) | 0.232 |
Data were presented as median (IQR) or n/N (%) (N represented data available for analysis per variable); yrs, years; KE, knee extension; HF, hip flexion; FF, finger flexion; NF, neck flexion; IBMFRS, inclusion body myositis functional rating scale; CK, creatine kinase; RV, rimmed vacuoles; MHC, major histocompatibility.
*Adjusted for disease duration and age at onset, P = 0.004, OR = 8.35, 95% CI 1.94 to 35.95.
**Adjusted for disease duration, age at onset, P = 0.023, OR = 16.08, 95%CI 1.46 to 176.93. Additionally adjusted for sex, P = 0.171, OR = 5.49, 95% CI 0.48 to 62.80.
***Adjusted for disease duration, age at onset, and sex, P = 0.289, adjusted mean difference = -3.67, 95%CI -10.59 to 3.24, partial η2 = 0.03.
Bold values indicate statistically significant results with a P-value < 0.05.
Anti-cN1A antibodies in IBM
Thirty patients were tested for anti-cN1A antibodies. (Table 3). Twenty patients (66.7%) were seropositive and 10 (33.3%) were seronegative. Specifically, the positivity of anti-cN1A antibody was detected in 7/14 (50.0%) patients by ELISA and 13/16 (81.3%) patients by CBA. After adjustment for disease duration and age at onset, the seropositive group was associated with a later age at onset (P = 0.034). Histopathological analyses showed that the seropositive group had a higher score for COX-negative fibers (≥ 3) compared with the seronegative group (P = 0.039). However, this difference was no longer significant after adjustment for age at biopsy.
Table 3.
Comparison of clinical and pathological characteristics between the subgroups of Anti-cN1A antibodya.
| Characteristics | cN1A-negative | cN1A-positive | P |
|---|---|---|---|
| Demographics, n = 30 | |||
| Female (%) | 6/10(60) | 7/20(35) | 0.255 |
| Age at onset, yrs | 49 ± 8.4 | 57.3 ± 9.6 | 0.019* |
| Disease duration, yrs | 8(1,12) | 4.5(1,6) | 0.155 |
| Age at biopsy, yrs | 55.8 ± 9.1 | 61.5 ± 10.2 | 0.143 |
| Clinical feature, n =30 | |||
| KE weakness (%) | 9/10(90) | 17/20(85) | >0.999 |
| HF weakness (%) | 10/10(100) | 20/20(100) | — |
| KE ≤ HF (%) | 7/10(70) | 15/20(75) | >0.999 |
| FF weakness (%) | 10/10(100) | 19/20(95) | >0.999 |
| NF weakness (%) | 7/10(70) | 13/20(65) | >0.999 |
| Strength sum scores | 101.25(70.7,109.8) | 102.4(82.4,117.6) | 0.307 |
| Upper limb muscle strength | 59.875(33.2,65.5) | 61.1(44.4,70) | 0.448 |
| Lower limb muscle strength | 42(25,47) | 42.25(33.5,48.5) | 0.619 |
| IBMFRS scores | 34.5(29,42) | 34(25,43) | 0.812 |
| Dysphagia (%) | 5/10(50) | 6/20(30) | 0.425 |
| CK, IU/L | 932.5(38,2180) | 559.5(106,4000) | 0.448 |
| Muscle biopsy feature | |||
| Endomysial inflammation (%), n=30 | 10/10(100) | 20/20(100) | — |
| Perimysial inflammation (%), n=30 | 2/10(20) | 7/20(35) | 0.675 |
| Invasion or surrounding of non-necrotic muscle fibers (%), n=30 | 9/10(90) | 18/20(90) | >0.999 |
| Endomysial fibrosis (%), n=24 | 7/8(87.5) | 11/16(68.8) | 0.621 |
| RV (%), n=30 | 7/10(70) | 18/20(90) | 0.300 |
| MHC-I positivity (%), n =28 | 9/9(100) | 19/19(100) | — |
| Mitochondrial abnormalities (%), n=26 | 7/9(77.8) | 17/17(100) | 0.111 |
| COX-negative fibers score ≥ 3(%), n = 23 | 2/8(25) | 11/15(73.3) | 0.039** |
| P62 deposits score ≥ 4(%), n = 22b | 2/8(25) | 10/14(71.4) | 0.074 |
| Deposition of the complement score > 2(%), n =23 | 1/8(12.5) | 7/15(46.7) | 0.176 |
Data were presented as median (IQR) or n/N (%) (N represented data available for analysis per variable); yrs, years; KE, knee extension; HF, hip flexion; FF, finger flexion; NF, neck flexion; IBMFRS, inclusion body myositis functional rating scale; CK, creatine kinase; RV, rimmed vacuoles; MHC, major histocompatibility; COX, cytochromec oxidase.
aThe positivity of anti-cN1A antibody was detected in 7/14 (50.0%) patients by ELISA and 13/16 (81.3%) patients by CBA.
bP62 immunostaining data were available in 22 patients. One case was excluded because the corresponding histological slides were no longer available for reassessment.
*Adjusted for sex and disease duration, P = 0.034, mean difference = -9.82, 95%CI -18.82 to -0.82, partial η2 = 0.162.
**Adjusted for sex, age at onset P = 0.036, OR = 0.08, 95%CI 0.01 to 0.85. Adjusted additionally for age at biopsy, P = 0.070, OR = 0.09, 95%CI 0.01 to 1.21.
Bold values indicate statistically significant results with a P-value < 0.05.
Complement deposition in IBM
The relationship between complement deposition and muscle strength were analyzed in 22 patients (Table 4 and Supplementary Table 6). The patients with higher complement deposition score (>2) were tended to show lower overall muscle strength (P = 0.050). After adjustment for sex, age at onset and disease duration, there was a statistically significant association between complement deposition and more severe decline in muscle strength in proximal upper limbs and distal lower limbs (P = 0.008 and P = 0.006). However, no significant differences were observed in other clinical or pathological features.
Table 4.
Comparison of clinical and pathological characteristics between the subgroups of complement deposition.
| Characteristics | Complement deposits score >2 | Complement deposits score ≤2 | P |
|---|---|---|---|
| Demographics, n = 23 | |||
| Female (%) | 3/8(37.5) | 7/15(46.7) | >0.999 |
| Age at onset, yrs | 56.4 ± 7.5 | 52.5 ± 12.0 | 0.414 |
| Disease Duration, yrs | 3.5(2.25,5) | 5(3,10) | 0.650 |
| Age at biopsy, yrs | 60.3 ± 7.9 | 58.1 ± 12.0 | 0.728 |
| Clinical feature, n = 23 | |||
| KE weakness (%) | 7/8(87.5) | 13/15(86.7) | >0.999 |
| HF weakness (%) | 8/8(100) | 15/15(100) | — |
| KE ≤ HF (%) | 6/8(75) | 12/15(80) | >0.999 |
| NF weakness (%) | 4/8(50) | 11/15(73.3) | 0.371 |
| Ankle dorsiflexion weakness (%) | 5/8(62.5) | 1/15(6.7) | 0.009* |
| Elbow flexion weakness (%) | 7/8(87.5) | 6/15(40) | 0.074 |
| Strength sum scores | 90.05(84.175,102.45) | 102.5(97.10,110) | 0.050 |
| Proximal upper limb muscle strength | 23.5(21.75,26.25) | 27(25,29) | 0.018** |
| Upper limb muscle strength | 53.85(45.975,61.125) | 61.25(55.6,66) | 0.058 |
| Distal lower limb muscle strength | 19.5(14.25,20) | 20(20,20) | 0.026*** |
| Lower limb muscle strength | 39.75(34.75,42.375) | 42.5(40,45) | 0.077 |
| IBMFRS scores | 34(33,36.75) | 34(30,39) | 0.334 |
| Dysphagia (%) | 2/8(25) | 6/15(40) | 0.657 |
| CK, IU/L | 686(330,1585) | 701(334,1937) | 0.513 |
| Muscle biopsy feature | |||
| Endomysial inflammation (%), n = 23 | 8/8(100) | 15/15(100) | — |
| Perimysial inflammation (%), n = 23 | 4/8(50) | 3/15(20) | 0.182 |
| Invasion or surrounding of non-necrotic muscle fibers (%), n = 23 | 7/8(87.5) | 13/15(86.7) | >0.999 |
| Endomysial fibrosis (%), n = 23 | 5/8(62.5) | 13/15(86.7) | 0.297 |
| RV (%), n = 23 | 8/8(100) | 11/15(73.3) | 0.257 |
| MHC-I positivity (%), n = 23 | 8/8(100) | 15/15(100) | — |
| Mitochondrial abnormalities (%), n = 23 | 7/8(87.5) | 14/15(93.3) | >0.999 |
| COX-negative fibers score ≥3 (%), n = 23 | 6/8(75) | 7/15(46.7) | 0.379 |
| p62 deposits score ≥ 4 (%), n =22a | 4/8(50) | 8/14(57.1) | >0.999 |
Data were presented as median (IQR) or n/N (%) (N represented data available for analysis per variable); yrs, years; KE, knee extension; HF, hip flexion; FF, finger flexion; NF, neck flexion; IBMFRS, inclusion body myositis functional rating scale; CK, creatine kinase; RV, rimmed vacuoles; MHC, major histocompatibility; COX, cytochromec oxidase.
ap62 immunostaining data were available in 22 patients. One case was excluded because the corresponding histological slides were no longer available for reassessment.
*Unadjusted comparison only. Logistic regression was not feasible because of complete separation caused by sparse events in this subgroup.
**Adjusted for sex, age at onset and disease duration, P = 0.008, mean difference = -3.77, 95%CI -6.44 to -1.10, partial η² = 0.356.
***Adjusted for sex, age at onset and disease duration, P = 0.006, mean difference = -2.53, 95%CI -4.23 to -0.84, partial η2 = 0.342.
Bold values indicate statistically significant results with a P-value < 0.05.
Discussion
This study characterized the clinical, pathological, and laboratory features of Chinese patients with IBM through a single-center retrospective cohort analysis. The proportion of patients who underwent muscle biopsy who were subsequently diagnosed with IBM in our center was 0.55% (36/6,535). This is lower than a previous report of 0.68% in another Chinese cohort (16). This confirms that IBM is a rare disease in the Chinese population. Due to the rarity of IBM, the sample size of most single-center studies was around 20 to 60 cases (14–16, 24), while only a few specialized centers reported larger cohorts with over 100 patients (20, 25). Demographic data revealed some differences compared with other populations. In this cohort, the male-to-female ratio was 1.4:1, slightly lower than the ratios in Caucasian cohorts (ranging from approximately 1.7:1 to 2.3:1) (5, 20, 26). The mean age at onset of our patients was 54.9 years, while the median or mean age at onset from previous studies was 58.7 to 68.8 years in Caucasian populations (5, 20, 26), and 62.4 to 64.6 years in Japanese cohorts (27, 28). The relatively earlier onset age in this cohort might be due to the inclusion of patients with onset age below 45 years according the revised 2024 ENMC criteria (2). Although a Korean cohort reported a comparable mean age at onset of 54 years (24), their finding might be limited by the small sample size. In our cohort, five patients (11.6%) in our cohort presented with first symptoms before age 45, which suggested the underestimation of early-onset cases. The overall mean age at onset in IBM might be earlier than that was currently reported. Recent studies demonstrated that patients with early onset were associated with more severe disease progression and greater mitochondrial abnormality burden (29, 30). This highlights the importance of early diagnosis and intervention to improve outcomes.
This study confirmed that Chinese IBM patients presented with the characteristically selective muscle weakness pattern, consistent with the reports from Caucasian, Japanese and Korean studies (5, 24, 26–28). The typical features of muscle weakness predominantly in knee extension and finger flexion were observed in the majority of this cohort, confirming this pattern as a core clinical feature of IBM among different populations. Interestingly, all patients in this cohort had weakness in hip flexion, and 88.4% of the patients with weakness in knee extension, while weakness in knee extension was worse than hip flexion in 76.6% of the patients. This indicated that quadriceps were more severely affected while iliopsoas were more frequently affected. This has not been described in previous studies (5, 24, 26–28). Additionally, neck flexion weakness was presented in 69.8% of patients in this cohort, which indicated the involvement of neck flexors might be a common feature in IBM and required careful examination at routine clinical practice.
Dysphagia has been reported to occur in 30% to 80% of IBM patients in previous studies, with higher prevalence associated with longer disease duration (12, 28, 29, 31, 32). In this cohort, 39.5% of patients developed dysphagia during the disease course, while only 4.7% reported it as a symptom at onset. This proportion of initial dysphagia presentation appears lower than that documented in prior reports (28, 31). Unadjusted analysis revealed that patients with dysphagia had weaker upper limb strength, particularly in wrist flexion. However, the statistical significance disappeared after adjustment for disease duration, age at onset, and sex. These findings suggested that dysphagia might reflect overall disease severity rather than representing an isolated symptom. Furthermore, multiple studies have found a direct link between dysphagia and aspiration pneumonia (32–34), which is also a leading cause of death in IBM (35). Therefore, early identifying dysphagia, especially when co-occurring with features like neck flexion weakness, is crucial for the early recognition of high-risk patients, and to take further intervention for complications and improving prognosis.
In this cohort, female patients were more prone to develop dysphagia, which is consistent with previous reports (5, 28). In addition, the female patients had a significantly higher risk of developing weakness in neck flexion than the males (P < 0.001). There was a significant association between dysphagia and neck flexion weakness (P = 0.005), however, the association was no longer significant after adjustment for sex (P = 0.171). This indicated that sex primarily influenced both symptoms. Previous studies suggested that estrogen deficiency in postmenopausal women could lead to neuromuscular impairment in cervical regions (36–38). Given the high prevalence of these symptoms in the female patients, we hypothesize that similar hormonal mechanisms may play a role in IBM, which potentially exacerbates muscle vulnerability in craniocervical regions. The exact pathophysiological link between dysphagia and neck muscle weakness in IBM requires further elucidation. Therefore, clinical management priorities should differ by sex, particularly monitoring dysphagia and neck flexion weakness in the female patients. Regarding the distribution of muscle weakness, our findings partially support previous conclusions. One study indicated that female patients have stronger finger flexor strength than males (20), and a similar trend was observed in our cohort, although it did not reach statistical significance. A recent study suggested that males are more likely to have quadriceps weakness (5), while this was not observed in our study.
The anti-cN1A antibody demonstrates relatively high specificity for IBM, but its diagnostic relevance remains controversial. This study found that seropositive patients had a significantly later age at onset (mean onset age of 57.3 years) after adjustment (P = 0.034). A similar finding has been reported by Felice et al. (14). No significant association was observed between antibody and sex, which was consistent with previous studies (7, 10, 11, 39). Several studies suggested a higher frequency of dysphagia in seropositive patients (11, 12, 40), and some reported association with facial muscle involvement (7). The patterns of muscle weakness associated with seropositive patients varied across different cohorts, including proximal upper limb weakness (7), finger flexion weakness (10, 28), or lower limb involvement (40). While in this cohort, no significant correlations were found between anti-cN1A antibody and specific patterns of muscle weakness. The prognostic significance of anti-cN1A antibodies also remains debated, with conflicting reports regarding survival (7, 10).
In muscle pathology, previous studies have reported a higher frequency of COX-deficient fibers in seropositive patients (7, 10). In our cohort, a similar trend was observed, but it did not reach statistical significance after adjustment for age at biopsy (P = 0.070). These findings suggested that both anti-cN1A antibody and age might play a role in COX deficiency in IBM. There might be differences in pathogenic mechanisms between anti-cN1A subgroups. Paul et al. further indicated that seropositive patients exhibited more frequent auto-aggressive inflammation on muscle biopsy, though not as an isolated pathological feature (13). However, our study found no statistically significant association between antibody status and focal invasion of inflammatory cells or MHC expression, which was consistent with most reports (10, 13, 14, 28). Additionally, high levels of complement deposition (score>2) were observed almost exclusively in seropositive patients. Although this finding did not reach statistical significance, it may provide a clue to the interaction between antibody and complement activation.
Although complement deposition has been reported in isolated IBM cases (41, 42), it has seldom been considered a hallmark pathological feature of IBM (43). Recently, Syed et al. reported the C5b-9 upregulation in 17 of 20 IBM patients (44, 45). Our study further analyzed complement deposition in a defined Chinese IBM cohort. Complement deposition was observed in 77.4% of cases. Patients with higher levels of complement deposition developed more severe muscle weakness with reduced overall muscle strength, especially in elbow flexion and ankle dorsiflexion. These findings highlighted a potential association between complement deposition and disease severity in IBM. Although the complement terminal complex C5b-9 can cause membrane injury, IBM is primarily considered a T-cell mediated and degenerative process (2). Consequently, the complement deposition is likely a secondary phenomenon associated with muscle fiber injury rather than a primary driver. No complement targeting therapies have demonstrated clinical efficacy in IBM to date (44). Therefore, the potential role of complement in pathophysiology of IBM requires further investigation.
Several limitations of this study should be acknowledged. First, as a single-center retrospective cohort analysis, the study carries a risk of selection bias. Second, although this represents the largest IBM cohort in China so far, the limited sample size may have reduced statistical power. In addition, correlation findings should also be interpreted with caution due to the small sample size. In some subgroup analyses, this limitation resulted in complete separation, preventing valid estimation in multivariable models. Furthermore, due to the retrospective design, some data were missing, and the anti-cN1A antibody was tested by two different methods (ELISA and CBA). Previous studies indicated that while the sensitivity of these two assays might be comparable, CBA demonstrated higher specificity for the diagnosis of IBM (2, 28, 39). These limitations highlight the need for prospective multi-center studies across the nation with larger sample sizes, and a standardized antibody testing method is required in future.
Conclusion
In conclusion, this single-center retrospective study provides a comprehensive profile of a Chinese IBM cohort on clinical, serological, and myopathological characteristics. Our findings further confirmed the clinical heterogeneity of IBM across different ethnicities. We reported a high frequency of complement deposition in muscle tissue and suggested its involvement in local immune-inflammatory processes and disease severity. Future prospective and multi-center studies with larger sample sizes are necessary to validate these observations and to investigate the disease progression and prognosis of IBM patients in China.
Acknowledgments
We thank the patients and their families for participating in our study. We also wish to acknowledge our colleagues, Ms Jin Liu, Ms Qingqing Wang, and Ms Yuehuan Zuo from the Department of Neurology for processing the muscle biopsy slides and Dr Jin Xu from Laboratory of Electron Microscopy to provide the electron microscopy samples.
Funding Statement
The author(s) declared that financial support was received for this work and/or its publication. QG is supported by the National Natural Science Foundation of China (81801243). ZW is supported by National Natural Science Foundation of China (82430059) and National High Level Hospital Clinical Research Funding (High Quality Clinical Research Project of Peking University First Hospital (2023HQ03).
Footnotes
Edited by: Rosaria Talarico, ERN ReCONNET Coordination Team, Italy
Reviewed by: Elina Tan, Sir Charles Gairdner Hospital, Australia
Cleonisio Rodrigues, Fortaleza General Hospital, Brazil
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by Institutional Review Board of Peking University First Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
HQ: Writing – review & editing, Methodology, Formal analysis, Writing – original draft, Data curation. SY: Writing – original draft, Data curation, Writing – review & editing, Formal analysis, Validation. XG: Data curation, Formal analysis, Writing – original draft. YL: Writing – review & editing, Resources. YaZ: Writing – review & editing, Resources. MY: Writing – review & editing, Resources. YiZ: Writing – review & editing, Resources. LM: Writing – review & editing, Resources. HL: Writing – review & editing, Resources. JD: Writing – review & editing. WZ: Writing – review & editing, Resources. ZW: Project administration, Methodology, Resources, Funding acquisition, Supervision, Writing – review & editing. YY: Writing – review & editing, Methodology, Supervision, Project administration, Resources. QG: Methodology, Data curation, Writing – review & editing, Supervision, Investigation, Validation, Writing – original draft, Resources, Project administration, Funding acquisition.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2026.1782053/full#supplementary-material
References
- 1. Greenberg SA. Inclusion body myositis: Clinical features and pathogenesis. Nat Rev Rheumatol. (2019) 15:257–72. doi: 10.1038/s41584-019-0186-x, PMID: [DOI] [PubMed] [Google Scholar]
- 2. Lilleker JB, Naddaf E, Saris CGJ, Schmidt J, De Visser M, Weihl CC, et al. 272nd ENMC international workshop: 10 years of progress - revision of the ENMC 2013 diagnostic criteria for inclusion body myositis and clinical trial readiness. 16–18 june 2023, hoofddorp, the Netherlands. Neuromuscul Disord. (2024) 37:36–51. doi: 10.1016/j.nmd.2024.03.001, PMID: [DOI] [PubMed] [Google Scholar]
- 3. Huntley ML, Gao J, Termsarasab P, Wang L, Zeng S, Thammongkolchai T, et al. Association between TDP-43 and mitochondria in inclusion body myositis. Lab Invest. (2019) 99:1041–8. doi: 10.1038/s41374-019-0233-x, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Kleefeld F. Mitochondrial damage is associated with an early immune response in inclusion body myositis. Brain (2025) 148:3199–3214. doi: 10.1093/brain/awaf118, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Lindgren U, Pullerits R, Lindberg C, Oldfors A. Epidemiology, survival, and clinical characteristics of inclusion body myositis. Ann Neurol. (2022) 92:201–12. doi: 10.1002/ana.26412, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Benjamin Larman H, Salajegheh M, Nazareno R, Lam T, Sauld J, Steen H, et al. Cytosolic 5′-nucleotidase 1A autoimmunity in sporadic inclusion body myositis. Ann Neurol. (2013) 73:408–18. doi: 10.1002/ana.23840, PMID: [DOI] [PubMed] [Google Scholar]
- 7. Lilleker JB, Rietveld A, Pye SR, Mariampillai K, Benveniste O, Peeters MTJ, et al. Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis. Ann Rheum Dis. (2017) 76:862–8. doi: 10.1136/annrheumdis-2016-210282, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Lloyd TE, Christopher-Stine L, Pinal-Fernandez I, Tiniakou E, Petri M, Baer A, et al. Cytosolic 5′-nucleotidase 1A as a target of circulating autoantibodies in autoimmune diseases. Arthritis Care Res. (2016) 68:66–71. doi: 10.1002/acr.22600, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Muro Y, Nakanishi H, Katsuno M, Kono M, Akiyama M. Prevalence of anti-NT5C1A antibodies in Japanese patients with autoimmune rheumatic diseases in comparison with other patient cohorts. Clin Chim Acta. (2017) 472:1–4. doi: 10.1016/j.cca.2017.07.002, PMID: [DOI] [PubMed] [Google Scholar]
- 10. Ikenaga C, Findlay AR, Goyal NA, Robinson S, Cauchi J, Hussain Y, et al. Clinical utility of anti-cytosolic 5’-nucleotidase 1A antibody in idiopathic inflammatory myopathies. Ann Clin Transl Neurol. (2021) 8:571–8. doi: 10.1002/acn3.51294, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Goyal NA, Cash TM, Alam U, Enam S, Tierney P, Araujo N, et al. Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement. J Neurol Neurosurg Psychiatry. (2016) 87:373–8. doi: 10.1136/jnnp-2014-310008, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Lucchini M, Maggi L, Pegoraro E, Filosto M, Rodolico C, Antonini G, et al. Anti-cN1A antibodies are associated with more severe dysphagia in sporadic inclusion body myositis. Cells. (2021) 10:1146. doi: 10.3390/cells10051146, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Paul P, Liewluck T, Ernste FC, Mandrekar J, Milone M. Anti-cN1A antibodies do not correlate with specific clinical, electromyographic, or pathological findings in sporadic inclusion body myositis. Muscle Nerve. (2021) 63:490–6. doi: 10.1002/mus.27157, PMID: [DOI] [PubMed] [Google Scholar]
- 14. Felice KJ, Whitaker CH, Wu Q, Larose DT, Shen G, Metzger AL, et al. Sensitivity and clinical utility of the anti-cytosolic 5′-nucleotidase 1A (cN1A) antibody test in sporadic inclusion body myositis: Report of 40 patients from a single neuromuscular center. Neuromuscul Disord. (2018) 28:660–4. doi: 10.1016/j.nmd.2018.06.005, PMID: [DOI] [PubMed] [Google Scholar]
- 15. Eura N, Sugie K, Kinugawa K, Nanaura H, Ohara H, Iwasa N, et al. Anti-cytosolic 5’-nucleotidase 1A (cN1A) positivity in muscle is helpful in the diagnosis of sporadic inclusion body myositis: A study of 35 Japanese patients. J Neurol Neurosci. (2016) 07:155–159. doi: 10.21767/2171-6625.1000155 [DOI] [Google Scholar]
- 16. Li K, Pu C, Huang X, Liu J, Mao Y, Lu X. Clinicopathologic features of sporadic inclusion body myositis in China. Neurol Neurochir Pol. (2015) 49:245–50. doi: 10.1016/j.pjnns.2015.06.004, PMID: [DOI] [PubMed] [Google Scholar]
- 17. Zheng RL, Yan CZ, Lv HD, Lv H, Bi H, Yuan Y. Clinical and myopathological features in sporadic inclusion body myositis: a 7-case report. Chin J Neurol. (2007) 40:796–9. doi: 10.3760/j.issn\:1006-7876.2007.12.002 [DOI] [Google Scholar]
- 18. Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, et al. Reliability and validity of the medical research council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. (2008) 40:665–71. doi: 10.2340/16501977-0235, PMID: [DOI] [PubMed] [Google Scholar]
- 19. Jain M, Smith M, Cintas H, Koziol D, Wesley R, Harris-Love M, et al. Intra-rater and inter-rater reliability of the 10-point manual muscle test (MMT) of strength in children with juvenile idiopathic inflammatory myopathies (JIIM). Phys Occup Ther Pediatr. (2006) 26:5–17. doi: 10.1080/J006v26n03_02, PMID: [DOI] [PubMed] [Google Scholar]
- 20. Michelle EH, Pinal-Fernandez I, Casal-Dominguez M, Albayda J, Paik JJ, Tiniakou E, et al. Clinical subgroups and factors associated with progression in patients with inclusion body myositis. Neurology. (2023) 100:1406-e1417. doi: 10.1212/WNL.0000000000206777, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Pinto MV, Laughlin RS, Klein CJ, Mandrekar J, Naddaf E. Inclusion body myositis: Correlation of clinical outcomes with histopathology, electromyography and laboratory findings. Rheumatology. (2022) 61:2504–11. doi: 10.1093/rheumatology/keab754, PMID: [DOI] [PubMed] [Google Scholar]
- 22. Yang M, Ji S, Xu L, Zhang Q, Li Y, Gao H, et al. The clinicopathological distinction between immune-mediated necrotizing myopathy and limb–girdle muscular dystrophy R2: Key points to prevent misdiagnosis. J Clin Med. (2022) 11:6566. doi: 10.3390/jcm11216566, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Lindvall B. Immunohistological studies on muscle biopsies : Clinical and pathogenetic aspects on inflammatory myopathies/björn lindvall. Univ. (2002) 23. [Google Scholar]
- 24. Lee S-A, Lee HJ, Suh BC, Shin HY, Kim SW, Yoon B-A, et al. Clinical significance of anti-NT5c1A autoantibody in korean patients with inflammatory myopathies. PloS One. (2023) 18:e0284409. doi: 10.1371/journal.pone.0284409, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Sangha G, Yao B, Lunn D, Skorupinska I, Germain L, Kozyra D, et al. Longitudinal observational study investigating outcome measures for clinical trials in inclusion body myositis. J Neurol Neurosurg Psychiatry. (2021) 92:854–62. doi: 10.1136/jnnp-2020-325141, PMID: [DOI] [PubMed] [Google Scholar]
- 26. Oldroyd AGS, Lilleker JB, Williams J, Chinoy H, Miller JAL. Long-term strength and functional status in inclusion body myositis and identification of trajectory subgroups. Muscle Nerve. (2020) 62:76–82. doi: 10.1002/mus.26859, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Hori H, Yamashita S, Tawara N, Hirahara T, Kawakami K, Nishikami T, et al. Clinical features of Japanese patients with inclusion body myositis. J Neurol Sci. (2014) 346:133–7. doi: 10.1016/j.jns.2014.08.009, PMID: [DOI] [PubMed] [Google Scholar]
- 28. Yamashita S, Tawara N, Sugie K, Suzuki N, Nishino I, Aoki M. Impact of sex, age at onset, and anti-cN1A antibodies on sporadic inclusion body myositis. J Neurol Sci. (2024) 464:123164. doi: 10.1016/j.jns.2024.123164, PMID: [DOI] [PubMed] [Google Scholar]
- 29. Lindgren U, Hedberg-Oldfors C, Pullerits R, Lindberg C, Oldfors A. Inclusion body myositis with early onset: A population-based study. J Neurol. (2023) 270:5483–92. doi: 10.1007/s00415-023-11878-w, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Cox FM, Titulaer MJ, Sont JK, Wintzen AR, Verschuuren JJGM, Badrising UA. A 12-year follow-up in sporadic inclusion body myositis: An end stage with major disabilities. Brain. (2011) 134:3167–75. doi: 10.1093/brain/awr217, PMID: [DOI] [PubMed] [Google Scholar]
- 31. Cox FM, Verschuuren JJ, Verbist BM, Niks EH, Wintzen AR, Badrising UA. Detecting dysphagia in inclusion body myositis. J Neurol. (2009) 256:2009–13. doi: 10.1007/s00415-009-5229-9, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Alamr M, Pinto MV, Naddaf E. Atypical presentations of inclusion body myositis: Clinical characteristics and long-term outcomes. Muscle Nerve. (2022) 66:686–93. doi: 10.1002/mus.27716, PMID: [DOI] [PubMed] [Google Scholar]
- 33. Peng A, Koffman BM, Malley JD, Dalakas MC. Disease progression in sporadic inclusion body myositis: Observations in 78 patients. Neurology. (2000) 55:296–8. doi: 10.1212/WNL.55.2.296, PMID: [DOI] [PubMed] [Google Scholar]
- 34. Dobloug GC, Garen T, Brunborg C, Gran JT, Molberg Ø. Survival and cancer risk in an unselected and complete norwegian idiopathic inflammatory myopathy cohort. Semin Arthritis Rheum. (2015) 45:301–8. doi: 10.1016/j.semarthrit.2015.06.005, PMID: [DOI] [PubMed] [Google Scholar]
- 35. Naddaf E, Shelly S, Mandrekar J, Chamberlain AM, Hoffman EM, Ernste FC, et al. Survival and associated comorbidities in inclusion body myositis. Rheumatology. (2022) 61:2016–24. doi: 10.1093/rheumatology/keab716, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Kranjčević J-K, Čonkaš J, Ozretić P. The role of estrogen and estrogen receptors in head and neck tumors. Cancers. (2024) 16:1575. doi: 10.3390/cancers16081575, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Wakabayashi H, Kakehi S, Nagano A, Kishima M, Itoda M, Nishioka S, et al. Age and sex differences in sarcopenic dysphagia: A secondary data analysis. J Gen Fam Med. (2024) 25:343–50. doi: 10.1002/jgf2.722, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Tanrıverdi M, Heybeli C, Çalım ÖF, Durna M, Özturan O, Soysal P. The relationship between oropharyngeal dysphagia and dehydration in older adults. BMC Geriatr. (2024) 24:885. doi: 10.1186/s12877-024-05492-2, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Tawara N, Yamashita S, Zhang X, Korogi M, Zhang Z, Doki T, et al. Pathomechanisms of anti–cytosolic 5′-nucleotidase 1A autoantibodies in sporadic inclusion body myositis. Ann Neurol. (2017) 81:512–25. doi: 10.1002/ana.24919, PMID: [DOI] [PubMed] [Google Scholar]
- 40. Dejthevaporn R, Shah S, Wastling S, Thornton J, Yousry T, Morrow JM, et al. SAT0332 antibodies against cytosolic 5’-nucleotidase 1a in sporadic inclusion body myositis: association with clinical and MRI features. Ann Rheum Dis. (2020) 79:1112. doi: 10.1136/annrheumdis-2020-eular.3399, PMID: 41686241 [DOI] [Google Scholar]
- 41. Law C, Li H, Bandyopadhyay S. Coexistence of TDP-43 and C5b-9 staining of muscle in a patient with inclusion body myositis. BMJ Case Rep. (2021) 14:e238312. doi: 10.1136/bcr-2020-238312, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Buchman S, Bandyopadhyay S, Baccon J, Wicklund M. A surprising case of inclusion body myositis with positive endomysial C5b-9 staining. Muscle Nerve. (2016) 53:991–2. doi: 10.1002/mus.25013, PMID: [DOI] [PubMed] [Google Scholar]
- 43. Nelke C, Schmid S, Kleefeld F, Schroeter CB, Goebel H-H, Hoffmann S, et al. Complement and MHC patterns can provide the diagnostic framework for inflammatory neuromuscular diseases. Acta Neuropathol (Berl). (2024) 147:15. doi: 10.1007/s00401-023-02669-8, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Chen JY, Sanghani N, Palmer K, Li Y, Lin F, Abbatemarco JR. Complement activation in immunological neurological disorders: Mechanisms and therapeutic strategies. Front Neurol. (2025) 16:1695461. doi: 10.3389/fneur.2025.1695461, PMID: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Syed A, Moore H, Gracia M, Hussain H, Al-Saffar A, Hammad Y. Complement activation in inclusion body myositis: A clinicopathological study. Muscle Nerve. (2023) 68:476–686. doi: 10.1002/mus.27968, PMID: 41767589 [DOI] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.