Abstract
Objective
Laboratory diagnostic markers and clinical presentations of Sjögren’s disease (SjD) may vary by sex. This study aimed to investigate the association between lnc-DC expression and female SjD and to evaluate its potential as a diagnostic biomarker in female SjD patients.
Methods
599 SjD patients were retrospectively analyzed in this cohort, additionally 337 healthy adults without autoimmune diseases served as the healthy control group (HC). Adjusted p - values are reported for all exploratory analyses. Associations between diverse clinical parameters and SjD occurrence among female SjD patients were assessed using Cox proportional hazards models. To account for multiple hypothesis testing across 40 comparisons, we applied the Benjamini-Hochberg false discovery rate (FDR) correction with q = 0.05. Subsequently, receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of lnc-DC expression levels in distinguishing female SjD patients.
Results
After a retrospective observation for median 44 months (Interquartile Range (IQR): 35–55 months), symptoms such as dry mouth, joint pain, reduced tear flow, elevated IgM concentrations, increased ESSDAI scores, and higher detection rates of rheumatoid factor (RF), anti-Ro52 antibody, and anti-SSA antibody were significantly more prevalent among female patients (all p < 0.05). Moreover, female participants exhibited substantially increased levels of lnc-DC expression (p < 0.001). In contrast, males displayed a higher prevalence of parotid gland enlargement and interstitial lung disease (ILD) (both p < 0.001). Cox proportional hazards models identified elevated lnc-DC expression as an independent predictor for SjD development in females (p < 0.001). After FDR correction, elevated lnc-DC remained significantly associated with SjD status (adjusted p < 0.001). Other biomarkers did not survive correction (adjusted p > 0.05). Additionally, ROC curve analysis demonstrated that elevated lnc-DC levels effectively distinguished female SjD patients, with an area under the curve (AUC) of 0.83, sensitivity of 78.64%, and specificity of 73.61%, p < 0.001.
Conclusions
Female SjD patients exhibited significantly elevated lnc-DC expression. When integrated with conventional serological markers, lnc-DC enhanced SjD diagnostic accuracy. These findings suggest lnc-DC as a sex-specific adjunct biomarker for SjD clinical diagnosis.
Keywords: Sjögren's disease, Long non-coding RNAs (lnc-DC), Gender, Biomarkers
Introduction
Sjögren’s disease (SjD) represents a prevalent chronic autoimmune condition characterized by dysfunction primarily of lacrimal and salivary glands, manifesting as symptoms including xerostomia, fatigue, and musculoskeletal discomfort. Globally, SjD affects between 0.05% and 1% of the population, positioning it as the connective tissue disease (CTD) with the highest prevalence [1]. SjD predominantly affects middle-aged and elderly females, with a prevalence of 0.33% − 0.77% in the Chinese population. The male-to-female ratio is approximately 1:9, with a recent study reporting a ratio of 1:22.9 [2, 3]. According to previous studies, clinical manifestations vary based on sex [4]. Females more commonly present with dry mouth, leukopenia, and positive auto-antibodies, whereas males frequently experience parotid gland enlargement and ILD. With advancing age, the proportions of auto-antibody positivity and elevated immunoglobulin IgG progressively increase, while rampant tooth decay, dry eyes, and ILD also tend to become more frequent [5]. In a recent Chinese survey involving 742 SjD patients, elderly-onset individuals exhibited higher rates of ILD and hepatic involvement [6]. In addition to susceptibility variations, clinical presentations of autoimmune diseases may differ by sex due to sex hormones [7–9], distinct immune modulation [10–12], sex-specific environmental exposures [13, 14], and X-chromosome gene effects [15, 16].
Long non-coding RNAs (lncRNAs) constitute RNA transcripts longer than 200 nucleotides without the ability to encode proteins, playing extensive roles in various physiological and pathological conditions [17–19]. Lnc-DC (long non-coding RNA in dendritic cells), first described by Wang et al. [20], is predominantly expressed in dendritic cells (DCs). Through comprehensive single-cell transcriptomics, this 1.5-kb transcript was mapped to human chromosome 17q, facilitating DC maturation by activating the STAT3 pathway. Earlier investigations have indicated that circulating lnc-DC levels may function as diagnostic markers in autoimmune diseases, including multiple sclerosis (MS) [21]. Given its stable and cell-specific expression pattern, we hypothesized a possible role for lnc-DC in autoimmune pathogenesis, meriting additional research.
Therefore, the objectives of this study were: (A) to investigate differences in lnc-DC expression between female and male patients with SjD; and (B) to evaluate the predictive significance and clinical applicability of lnc-DC expression levels for SjD in female patients during the observation period.
Materials and methods
Study participants
A cohort study conducted retrospectively obtained ethical clearance from the Ethics Committee of Xuzhou Central Hospital (No.: XZXY-LJ-2015-117-099), with all participants or their legal representatives providing signed informed consent. 627 SjD patients diagnosed from January 2016 to December 2022 at Xuzhou Central Hospital were preliminarily screened.
Inclusion criteria: All patients met the 2016 ACR-EULAR classification criteria for SjD [22], requiring either: (1). Positive serum autoantibodies, or (2). Labial gland biopsy with focal lymphocytic sialadenitis (focus score ≥ 1 foci/4 mm²). Exclusion Criteria: (1). Patients concurrently diagnosed with other systemic autoimmune disorders, such as idiopathic inflammatory myopathies, or diffuse connective tissue diseases (CTD); (2). individuals diagnosed with malignancy; and (3). insufficient clinical data.
After screening, 11 patients were excluded due to a history of autoimmune, hepatic, or renal disorders, five were removed due to duplication of data, and 12 were excluded due to insufficient clinical records. Ultimately, the analysis encompassed 599 patients (61 males, 10.2%; 538 females, 89.8%; Fig. 1). Additionally, 337 healthy adults without autoimmune diseases served as the healthy control group (HC), including 38 males (11.3%) and 299 females (88.7%).
Fig. 1.
Flow chart of the study population. * Patients with Sjögren’s disease were diagnosed in accordance with the American-European classification criteria
Study period and data collection
Clinical and laboratory parameters from 599 SjD patients were retrospectively retrieved from hospital databases over an observation window spanning January 2016 to December 2022. All analyzed data represent the most recent records within this period. Trained researchers systematically enrolled participants adhering strictly to the criteria outlined. Clinical information recorded during the initial hospital admission for each subject was retrieved through Xuzhou Central Hospital’s electronic patient records and hospital information system (HIS). Information collected comprised: (1). General epidemiological information. (2). Exocrine gland manifestations, exocrine gland involvement: Assessed by unstimulated salivary flow rate (≤ 0.1 mL/min) and Schirmer’s test (≤ 5 mm/5 min). Ocular involvement assessed Schirmer’s test I: Without anesthesia; ≤ 5 mm/5 min considered positive, Ocular Staining Score (OSS) Using lissamine green/fluorescein. (3). Symptoms of systemic involvement: fever, fatigue, arthralgia, ILD. (4). Laboratory examination: complete blood count (CBC): Sysmex XN-1000 analyzer (Sysmex Corp.), urinalysis: Automated urine sediment analysis (UF-5000, Sysmex), liver/kidney function: alanine aminotransferase (ALT), aspartate aminotransferase (AST): Roche Cobas c702 (Roche Diagnostics), creatinine, blood urea nitrogen (BUN): Enzymatic methods (Roche Cobas c702), autoantibodies: RF, IgA/IgG/IgM: Nephelometry (BN ProSpec, Siemens), anti-nuclear antibodies (ANA): Indirect immunofluorescence (HEp-2 cells, EUROPattern), Complement (C3/C4): Turbidimetric assay (Roche Cobas c702). (5). Histopathological evaluation: Labial gland biopsy: Performed under local anesthesia; ≥ 4 lobules required. Focus score calculation: staining: Hematoxylin & eosin (H&E), definition: ≥ 50 lymphocytes per 4 mm² as one focus, threshold: Focus score ≥ 1 foci/4 mm² for diagnosis, blinded assessment: Two independent pathologists (κ = 0.92). Hematologic abnormalities: leukopenia: WBC < 3.5 × 109/L, anemia: Hb < 130 g/L (male) or < 115 g/L (female), thrombocytopenia: PLT < 125 × 109/L, ESR > 15 mm/h (male) or > 15 mm/h (female), CRP > 8 mg/L, IgG > 16,200 mg/L, IgA > 3780 mg/L, IgM > 2630 mg/L, C3 < 700 mg/L, C4 < 160 mg/L. The diagnostic criteria of dry eye comprised Schimer Test < 5 mm/5min, and (or) positive corneal staining (> 4 van Bisjsterveld score). The positive criteria for labial gland biopsy covered index of lymphocyte infiltration in biopsy tissue > 1/4mm2.
Assessment of lnc-DC levels by quantitative PCR (qPCR)
Total RNA was isolated from 200 µL of EDTA-anticoagulated plasma samples using a PrimeScript™ RT reagent kit (Invitrogen), followed by reverse transcription into complementary DNA (cDNA). Lnc-DC expression levels were quantified via qPCR from plasma-derived RNA. qRT-PCR was conducted utilizing 96-well plates, employing primers specific for lnc-DC as follows: forward: 5’-CCCTAAGATCGTCCCTTCC-3’, reverse: 5’-CAACCCCTCTTCCCTGCC-3’, β-actin as follows: forward: 5’-CATCCTGCGTCTGGACCT-3’, reverse: 5’-TAATGTCACGCACGATTTCC-3’. PCR cycling comprised initial heat-denaturation at 95 °C for 5 min, succeeded by 42 amplification cycles involving denaturation at 95 °C for 10 s, annealing at 60 °C for 30 s, and elongation at 72 °C for 20 s. Expression levels of lnc-DC were quantified relative to an internal reference gene employing the 2−ΔΔCt calculation method.
Statistical analysis
Continuous variables were presented as either mean ± standard deviation (SD) or median and interquartile range (IQR), and analysed t-test, or one-way ANOVA. For variables analyzed using one-way ANOVA involving three or more groups, p-values from subsequent pairwise post-hoc tests were adjusted for multiple comparisons using the Bonferroni method, and the adjusted p-values (p_adj) are reported. Cox proportional hazards models, yielding hazard ratios (HR), were utilized to explore associations between various clinical indicators and outcomes, using retrospective observation period (median 44 months, IQR: 35–55 months), duration as the dependent factor. Cox proportional hazards models were used to assess the independent association between elevated lnc-DC expression and independent predictor for SjD development in females. Variables with p < 0.05 or deemed clinically relevant were retained in Cox proportional hazards models. Results are presented for Model 1 (unadjusted), Model 2 (adjusted for age and disease duration). Additionally, ROC curves were plotted to evaluate the diagnostic performance (specifically sensitivity and specificity) of lnc-DC levels in distinguishing female SjD patients. Continuous variables were compared using ANCOVA (adjusted for covariates) or Mann-Whitney U tests (non-normal data). Categorical data used Fisher’s exact test. Diagnostic performance was evaluated by ROC analysis with Youden-index optimized cut-offs. A threshold for statistical significance was established at p < 0.05. All analyses were performed using GraphPad Prism (version 8) and R software (v3.6.3).
Results
Basic characteristics of female and male patients at SjD diagnosis
A cohort consisting of 599 SjD-diagnosed individuals was monitored longitudinally for a median duration of 44 months (IQR: 35–55 months). Among the 599 patients, 541 (90.3%) experienced dry mouth, 522 (87.1%) had dry eyes, 110 (18.4%) presented with parotid gland enlargement, 187 (31.2%) had rampant dental caries, and 236 underwent lip gland biopsy, with 219 (92.8%) positive results. Systemic symptoms included fever, fatigue, arthralgia, ILD, hemopenia, liver involvement, and kidney involvement.
Female SjD patients had more frequent dry mouth and arthralgia, along with higher positivity rates of anti-SSA, anti-Ro52 and RF (all p < 0.05). Additionally, female patients exhibited elevated ESSDAI scores, IgM, and lnc-DC (all p < 0.05). Conversely, males had a higher prevalence of parotid gland enlargement, ILD, and decreased tear flow rate (all p < 0.05) (Table 1).
Table 1.
Clinical characteristics of study subjects of primary Sjögren’s disease patients by gender
| Characteristics | HC | Male (n = 61) | Female (n = 538) | p value |
|---|---|---|---|---|
| Age (years old) | 55.7 (42.3–61.6) | 56.5 (41.8–63.0) | 55.0 (45.0–59.5.0.5) | 0.461 |
| Dry mouth (%) | NA | 49/61 (80.3) | 492/538 (91.4) | 0.005 |
| Dry eye (%) | NA | 50/61 (82.0) | 472/538 (87.7) | 0.202 |
| Parotid gland enlargement, n (%) | NA | 18/61 (29.5) | 92/538 (17.1) | 0.018 |
| Rampant teeth n (%) | NA | 15/61 (24.6) | 172/538 (32.0) | 0.238 |
| Positive Labial gland biopsy n (%) | NA | 22/24 (91.7) | 197/212 (92.9) | 0.821 |
| Fever n (%) | NA | 11/61 (18.0) | 97/538 (18.0) | 1.000 |
| Fatigue n (%) | NA | 31/61 (50.8) | 296/538 (55.0) | 0.532 |
| Arthralgia n (%) | NA | 16/61 (26.2) | 219/538 (40.7) | 0.028 |
| Interstitial lung disease n (%) | NA | 32/61 (52.5) | 157/538 (29.2) | < 0.001 |
| anemia n (%) | 0/337 | 29/61 (47.5) | 245/538 (45.5) | 0.766 |
| Leukopenia n (%) | 0/337 | 8/61 (13.1) | 95/538 (17.7) | 0.373 |
| Anemia n (%) | 0/337 | 17/61 (27.9) | 141/538 (26.2) | 0.780 |
| Thrombocytopenia | 0/337 | 8/61 (13.1) | 58/538(10.8) | 0.581 |
| Liver involvement n (%) | 0/337 | 12/61 (19.7) | 119/538 (22.1) | 0.661 |
| Kidney involvement n (%) | 0/337 | 10/61 (16.4) | 75/538 (13.9) | 0.603 |
| Saliva flow rates (mL/min) | NA | 2.45 (2.2–2.8) | 2.5 (2.2–2.9) | 0.505 |
| Tear flow rates (mm/5min) | NA | 5.6 (4.8–6.3) | 5.1 (4.0–6.1.0.1) | 0.027 |
| ESSDAI (Mean ± SD) | NA | 5.6 (5.1–6.4) | 6.0 (5.2–6.9) | 0.043 |
| C3 (g/L) | NA | 1.34 (1.07–1.60) | 1.35 (1.08–1.64) | 0.912 |
| C4 (g/L) | NA | 0.26 (0.18–0.37) | 0.26 (0.17–0.42) | 0.960 |
| ESR (mm/h) | NA | 24.3 (21.1–28.2) | 24.6 (21.1–29.2) | 0.605 |
| IgG (g/L) | NA | 16.74 (15.17–18.80) | 17.01 (15.30–19.01.30.01) | 0.548 |
| IgA (g/L) | NA | 2.67 (2.05–4.24) | 3.11 (2.08–4.03) | 0.341 |
| IgM (g/L) | NA | 2.18 (1.70–3.37) | 2.92 (1.85–4.32) | 0.039 |
| Hs-CRP (mg/L) | NA | 7.2 (4.9–8.4) | 7.1 (5.0–8.7.0.7) | 0.960 |
| Anti-SSA n (%) | 0/337 | 32/61 (52.5) | 366/538 (68.0) | 0.015 |
| Anti-SSB n (%) | 0/337 | 17/61 (27.9) | 214/538 (39.8) | 0.070 |
| Anti-Ro52 n (%) | 0/337 | 20/61 (32.8) | 267/538 (49.6) | 0.013 |
| Anti-CENPB n (%) | 0/337 | 3/61 (4.9) | 47/538 (8.7) | 0.307 |
| anti-RNP n (%) | 0/337 | 4/61 (6.6) | 50/538 (9.3) | 0.479 |
| RF n (%) | 0/337 | 29/61 (47.5) | 371/538 (69.0) | 0.001 |
| ANA n (%) | 0/337 | 18/61 (29.5) | 220/538 (40.9) | 0.085 |
| Lnc-DC (RCI) | 1.04 (0.76–1.29) | 1.09 (0.85–1.49) | 1.88 (1.31–2.34) | < 0.001 |
Elevated lnc-DC expression and its association with female SjD patients
Compared with the healthy control (HC) group, elevated lnc-DC expression was significantly associated with an increased risk of SjD in female patients. This association persisted in both unadjusted (Model 1: Hazard Ratio [HR] = 1.470, 95% CI: 1.325–1.632, p < 0.001) and partially adjusted models accounting for age and disease duration (Model 2: HR = 1.469, 95% CI: 1.322–1.633, p < 0.001) using Cox proportional hazards regression (Table 2).
Table 2.
The factors independently associated with female Sjögren’s disease patients were investigated using the Cox proportional hazards models
| Characteristic | Model 1 | Model 2 | ||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Lnc-DC of HC | Ref | Ref | ||
| Lnc-DC of Female SjD | 1.470 (1.325–1.632) | < 0.001 | 1.469 (1.322–1.633) | < 0.001 |
Model 1, unadjusted; Model 2, adjusted for age and disease duration; Ref, Reference
Elevated lnc-DC expression and its diagnostic potential in SjD patients
The expressions of lnc-DC in 337 healthy controls (HC) and 599 SjD patients were analyzed by qRT-PCR. As shown in Fig. 2A, the levels of lnc-DC were significantly elevated in female SjD patients than in male SjD patients (1.09 [0.85, 1.49] vs.1.82 [1.31, 2.34], p < 0.001). Meanwhile, we observed that the difference in lnc-DC expression in plasma between males and females was not significant in the HC group (1.03 [0.77, 1.23] vs.1.05 [0.76, 1.31], p = 0.560).
Fig. 2.
A The relative expression of lnc-DC in male and female SjD patients, male and female HC that was determined by qRT-PCR. *** p < 0.001, B ROC analysis on the predictive capacity of lnc-DC (AUC = 0.83, 95% CI: 0.813–0.857, p < 0.001) for the occurrence of female Sjögren’s disease patients showed sensitivities of 78.46% and specificities of 73.61%, respectively
ROC analysis was used to evaluate the ability of lnc-DC to distinguish female SjD patients. Lnc-DC in females yielded an AUC of 0.83 (95% CI: 0.813–0.864; p < 0.001), with a sensitivity of 78.64% and specificity of 73.61%. The optimal diagnostic cut-off value for lnc-DC (> 1.34) was determined by maximizing the Youden index. In contrast, lnc-DC showed no significant discriminatory capacity in males (AUC = 0.57, 95% CI: 0.475–0.672; p = 0.077), indicating no diagnostic utility (Fig. 2B).
Discussion
SjD occurs predominantly in females, frequently presenting with insidious onset and diverse clinical manifestations. Sex differences influence disease susceptibility and clinical presentations, as well as immunological profiles [23]. Understanding clinical features in SjD patients according to sex can facilitate accurate disease assessment and management. Previous investigations into the clinical and serological characteristics of SjD patients stratified by sex yielded inconsistent conclusions, likely resulting from differences in study methodologies, patient selection criteria, sample sizes, and ethnic variations [24–28]. These variations highlight intrinsic limitations linked to the representativeness inherent in patient sampling methods. Therefore, the present research aimed to delineate both clinical and immunological characteristics of SjD by evaluating sex-dependent variations in clinical presentations and serological patterns within a representative population sample. The results showed significantly higher lnc-DC levels in female SjD patients. Furthermore, sex-related differences were explored in this cohort and validated in an independent cohort. Additionally, elevated lnc-DC levels were found to significantly predict SjD occurrence in females.
LncRNAs, critical gene regulatory factors, are involved in regulating numerous cellular functions and disease processes. Lnc-DC, a dendritic cell-specific long non-coding RNA initially reported by Wang et al. [20], is encoded on chromosome 17. Lnc-DC modulates dendritic cell differentiation by triggering activation of the STAT3 signaling pathway. Emerging evidence has underscored an expanding role of lnc-DC in autoimmune disease pathogenesis. Shaker and colleagues found notably increased lnc-DC serum concentrations in MS patients, implying its potential as a diagnostic indicator for MS [21]. Conversely, other investigations reported prominently decreased lnc-DC expression levels of SLE and RA patients; nonetheless, these reductions did not correlate significantly with increased risk for SLE or RA [29, 30].
To date, limited research has addressed potential sex differences in lnc-DC expression or function, particularly concerning sex hormone-mediated mechanisms.
Numerous studies confirm significant sex differences in immune responses. Importantly, sex hormones directly modulate the function and differentiation of dendritic cells; for instance, estrogen has been shown to promote their inflammatory capacity, while androgens can exert suppressive effects [31, 32]. Given that lnc-DC is a key regulator of DC development [20], we hypothesize that the female-biased expression we observe may be embedded within this sex-hormone-regulated framework, contributing to the higher prevalence of SjD in women. Although this study measured plasma lnc-DC as a non-invasive biomarker, we recognize that circulating lnc-DC levels may not reflect its transcriptional activity within dendritic cells. While the majority of plasma lnc-DC originates from DCs, it may also stem from the passive release by dead cells, active secretion via exosomes, or contributions from non-dendritic cell sources [33].
Previous studies have explored differences in clinical characteristics of SjD patients according to sex [34–36]. This study found significantly higher proportions of dry mouth, arthralgia, decreased tear flow rates, ESSDAI, IgM, anti-SSA, anti-Ro52, RF, and elevated lnc-DC levels in female patients compared with males. Conversely, male patients exhibited higher proportions of parotid gland enlargement and ILD, consistent with previous findings [3, 37, 38]. This is the first study to quantify these differences after adjusting for covariates. The results revealed higher lnc-DC levels in female SjD patients (p < 0.001). Additionally, the Cox proportional hazards model indicated that heightened expression of lnc-DC among female patients was significantly associated with SjD incidence (p < 0.001). ROC analysis further supported that lnc-DC levels robustly predicted SjD occurrence in female patients (p < 0.001).
Higher lnc-DC levels, particularly when measured in plasma, could potentially aid in distinguishing female SjD patients, especially in challenging cases. Further studies specifically designed to assess sensitivity and specificity in diagnostic cohorts are needed. The strong association observed between elevated lnc-DC levels and SjD status in female patients suggests its potential role as a disease-associated marker. This finding could support further investigation into whether lnc-DC correlates with disease status, which may aid in patient stratification for clinical management. Future studies should explore lnc-DC’s relationship with treatment response in SjD.
Conclusions
In conclusion, the present investigation highlights lnc-DC as an innovative and reliable biomarker for predicting SjD incidence in female patients. In SjD, significantly elevated lnc-DC expression levels were observed among female patients compared to males; this disparity persisted even after controlling for gender, and established RFs. The diagnostic potential of lnc-DC as a predictive biomarker will undergo further validation under funding from Xuzhou City’s Key Research and Development Program [grant KC22153].
The term of retrospective observation period
During the retrospective observation period (median 44 months), the clinical and laboratory data of 599 SjD patients recorded in the hospital database were retrospectively analyzed. As a retrospective analysis, our assessment of disease progression relied on documented clinical snapshots rather than standardized prospective monitoring. Future longitudinal studies with scheduled sampling are warranted.
Limitations
Several limitations remain and should be addressed in future research. First, data were obtained exclusively from our hospital, with over 95% Han ethnicity, introducing potential sampling bias. Differences in ethnicity, lifestyle, and medication use may have influenced the results. Second, limitations of this study include the single-center nature of laboratory testing. Additionally, patient grouping was based exclusively on routine clinical assessments rather than comprehensive disease evaluations. Therefore, future studies involving multiple centers and larger patient cohorts are necessary to validate and extend these findings. Additionally, although the current retrospective analysis had a large patient sample, only data from the initial hospitalization were included. Nevertheless, the results provide valuable references for clinical assessment and management of hospitalized SjD patients in China.
Acknowledgements
The authors thank all of the patients, nurses, doctors, investigators, and technicians involved in this work for their efforts in data and sample collection. We thank Zibo Yimore Translation CO.LTD for their expert linguistic refinement and editing of this manuscript. This service improved the clarity and readability of our work.
Clinical trial number
Not applicable.
Abbreviations
- SjD
Sjögren’s disease
- lnc-DC
Long non-coding RNAs
- CTD
Connective tissue disease
- ILD
Interstitial lung disease
- DC
Dendritic cells
- APCs
Antigen-presenting cells
- HC
Healthy control
- ESSDAI
EULAR SjD disease activity index
- C3
Complement C3
- C4
Complement C4
- ESR
Erythrocyte sedimentation rate
- IgG
Immunoglobulin (Ig)G
- IgA
Immunoglobulin (Ig)A
- IgM
Immunoglobulin (Ig)M
- Hs-CRP
High-sensitivity CRP
- Anti-CENPB
Anti-centromere protein B
- RF
Rheumatoid factor
- ANA
Anti-nuclear antibody
- RCI
Relative concentration index
- ROC
Receiver operating characteristic
- AUC
Area under the curve
- SE
Std. Error
- 95% CI
95% confidence interval
- RA
Rheumatoid arthritis
- SLE
Systemic lupus erythematosus
- HIS
Hospital information system
- ELISA
Enzyme-linked immunosorbent assay
- IQR
Interquartile range
- HR
Hazard ratio
- RCI
Relative concentration index
Authors’ contributions
BBZ and YF contributed equally to this study. BBZ, YF and YHC contributed to the conception and design of the work, data analysis, interpretation of the data, and manuscript writing. FG, PW, SXW and YL collected and analyzed data. JZ and YHC searched and interpreted the data and critically revised the manuscript. All authors approved the final version of the manuscript for publication and they agreed to be accountable for all aspects of the work. BBZ, YF and YHC were the guarantors of this study, and as such, had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. All authors reviewed the manuscript.
Funding
This study was supported by the Key Research and Development Program of Xuzhou City [grant numbers KC22153]. The authors declare that there are no conflicts of interest.
Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was approved by the Institutional Ethics Committee ofXuzhou Central Hospital [XZXY-LJ-2015-117-099], and conforms to the ethical guidelines of the Declaration of Helsinki. Requirement for individual patient consent forms was waived due to the retrospective, observational nature of the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Beibei Zu and Yu Fu contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.