Tracheobronchial infectious diseases in adult-onset immunodeficiency with anti-interferon-gamma autoantibodies

Abstract

Background

Anti-interferon (IFN)-γ autoantibodies predispose subjects to infections caused by opportunistic intracellular pathogens and lead to the involvement of multiple well-recognized organs, such as the lungs, skin, and lymph nodes. However, the clinical characteristics of tracheobronchial involvement remain unrecognized.

Methods

A retrospective study was conducted between February 2016 and September 2024, enrolling patients with anti-IFN-γ autoantibodies who had documented evidence of tracheobronchial involvement. The clinical data were analyzed, including demographic information, clinical manifestations, laboratory results, chest computed tomography images, bronchoscopy findings, treatments, and clinical outcomes.

Results

A total of 33 patients were enrolled, with a mean age of 51.73 years old. The top five reported symptoms were cough, expectoration, fever, dyspnea, and fatigue. Laboratory tests showed elevated white blood cells, C-reactive protein, erythrocyte sedimentation rate, globulin, and immunoglobulin G. The detected pathogens included commonly reported opportunistic pathogens, such as Talaromyces marneffei (57.58%) and nontuberculous mycobacteria (42.42%), as well as the conventional pathogens typically found in patients without immunodeficiency diseases. Masses, nodules, and tracheobronchial stenosis were commonly seen on chest computed tomography scans and during bronchoscopy, directly indicating airway involvement. The predominant pathological results of the tracheobronchial lesions were chronic inflammation, with a small subset showing granuloma formation and abscess formation. Twenty-six patients (78.79%) achieved clinical improvement. Adverse events related to the therapeutic drug were reported in 30.3% of patients, with no life-threatening events.

Conclusions

Tracheobronchial lesions are characterized by masses, nodules, and tracheobronchial stenosis visualized during bronchoscopy, as well as inflammatory changes confirmed by pathologic examinations. Clinicians should be vigilant for tracheobronchial infections, particularly those caused by Talaromyces marneffei and nontuberculous mycobacteria. Pathogen-targeted therapy shows therapeutic benefits but requires close monitoring for drug-related toxicities.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-025-11523-z.

Introduction

The patient with anti-interferon (IFN)-γ autoantibodies (AIGAs) who developed severe mycobacterial infection was first described in 2004 [1], and AIGAs were considered to attenuate IFN-γ-mediated immunity against invading pathogens. A growing number of studies have reported the clinical and immunological characteristics of the immunodeficiency secondary to AIGAs. The main published cohort studies and sporadic cases predominantly originated from Southeast Asia and South China [2–4], which suggests potentially distinct functions of specific genes. HLA-DRB1*16:02 and HLA-DQB1*05:02 were more frequent in the AIGA-positive patients compared with healthy subjects [5]. Though the cause of AIGA production remains unclear, the titers of AIGAs decreased significantly during clinical improvement and increased as the disease progressed [6], indicating their predictive value for disease activity.

AIGAs predispose individuals to infections with nontuberculous mycobacteria (NTM) and Talaromyces marneffei (TM), the two most common pathogens, as well as other opportunistic infections [7]. Lymphadenopathy and pulmonary symptoms occurred in 74.4% and 67.5% of cases, respectively [7]. However, the clinical characteristics of airway involvement are rarely mentioned or are only discussed in the context of the pulmonary involvement. Furthermore, although bronchoscope enables visualization of tracheobronchial lesions, diagnosis is often delayed or misdiagnosed as malignancy. Therefore, this study aims to summarize the clinical features of airway lesions in AIGA-positive patients.

Materials and methods

Study population

We retrospectively collected clinical information of AIGA-positive patients with airway involvement at the First affiliated hospital of Guangxi Medical University between February 2016 and September 2024. Written informed consent was obtained from all participants. All data were obtained from medical record system at the time of initial diagnosis, including demographic information, clinical manifestations, laboratory results, chest computed tomography (CT) images, bronchoscopy findings, treatments, and clinical outcomes. The inclusion criteria were patients diagnosed with AIGA-related immunodeficiency syndrome and occurrence of airway involvement. Diagnosis of AIGA-related immunodeficiency syndrome required both positive enzyme-linked immunosorbent assay (ELISA) results and neutralizing capacity confirmed by Western blotting. Airway involvement was defined as meeting at least one of the following criteria: (a) visible tracheobronchial mass or nodules on bronchoscopy; (b) tracheobronchial stenosis confirmed by chest CT or bronchoscopy. Subjects under 18 years old of age or with human immunodeficiency virus infection were excluded.

Clinical assessment

The affected sites were confirmed by a series of tests—including chest CT, ultrasound, cultures (primarily of samples from infected areas like blood and skin), bone emission CT, and histopathological examination—that revealed abnormalities. In addition, any such abnormalities that could be explained by other diseases were not included among the affected sites. Finally, patients were followed during the first month after discharge and were subsequently assessed for clinical outcome. Clinical outcomes were categorized using the following criteria: (a) Clinical improvement: partial or complete recovery from the condition causing hospitalization, with no new signs or symptoms; (b) Acute exacerbation: hospital readmission due to worsening symptoms; (c) Death.

Detection of AIGAs

Blood samples were collected in 5 ml anticoagulant tubes. Indirect ELISA was performed to determine whether AIGAs test was positive. Western blotting was further utilized to detect the neutralizing capacity of AIGAs when the result of indirect ELISA was positive. The experimental methods used in this study were previously reported by our team [3].

Statistical analysis

All statistical analyses were performed using SPSS (Version 27.0). Quantitative data with normal distribution are expressed as mean ± standard deviation, while non-normally distributed quantitative data are reported as median (25th–75th percentiles). Categorical variables were described using frequencies and percentages.

Results

Demographics, clinical characteristics, and laboratory results of participants

A total of 160 AIGA-positive patients were initially screened in the study. Thirty-four patients were identified with airway involvement, but one subject was excluded due to incomplete clinical information. Thus, 33 patients were enrolled. The demographic information of the included 33 patients is shown in Table 1. The study included 19 males (57.58%) and 14 females (42.42%), with a mean age of 51.73 years. Of these patients, the Zhuang ethnic group constituted the majority (51.52%), while the rest included the Han ethnic group (45.45%) and the Yao ethnic group (3.03%). Nineteen patients (57.58%) resided in rural areas and engaged in physical jobs, while 14 (42.42%) lived in cities and engaged in non-physical jobs. Only 3 patients reported contact with bamboo rats, 2 had no such contact history, and contact history was unclear for the remaining 28 patients. Thirteen patients (39.39%) had more than one underlying disease, including hypertension (n = 6), chronic obstructive pulmonary disease (COPD; n = 1), bronchiectasis (n = 1), bronchial asthma (n = 1), pulmonary embolism (n = 1), erythema nodosum (n = 1), chronic gastritis (n = 2), hepatitis B surface antigen carrier status (n = 2), and cerebral infarction (n = 1). Fifteen patients (45.45%) reported a smoking history, whereas 18 (54.55%) were non-smokers.

Table 1.

Demographic characteristics of participants

Variables/N1, N2, N3…	N 1	N 2	N 3	N1/Ntotol
Sex/female, male	14	19	NA	42.42%
Ethnic origin/Han, Zhuang, othersa	15	17	1	45.45%
Residence/rural, urban	19	14	NA	57.58%
Occupation/Physical jobs, non-physical jobs	19	14	NA	57.58%
Contact history with bamboo rat/yes, no, unclear	3	2	28	9.09%
Underlying diseases/yes, no	13	20	NA	39.39%
Smoking/yes, no	15	18	NA	45.45%

The variable N1 denotes the count of the first categorical element within each variable (e.g., female in the sex variable)

NA: Not Applicable

^aAccording to data from the Guangxi Zhuang Autonomous Region Bureau of Statistics, the Han ethnic group constitutes the majority in Guangxi, accounting for 62.48%. The Zhuang ethnic group, as the largest minority, constitutes 31.36% of the population (Source: http://tjj.gxzf.gov.cn/zxfb/t8851187.shtml)

Cough (96.97%), expectoration (75.76%), fever (54.55%), dyspnea (42.42%), and fatigue (36.36%) were the top five reported symptoms. Physical examination revealed crackles in 10 cases (30.3%), rhonchi in 1 case (3.03%), and signs of pleural effusion in 4 cases (12.12%). Laboratory data (Table 2) showed that most patients exhibited remarkably elevated inflammatory markers, including increased white blood cell counts (81.82%), erythrocyte sedimentation rate (93.33%), and C-reactive protein (90.91%). Lymphocyte counts were available for 24 patients, and only a limited subset of these patients exhibited CD4 + T-cell counts (33.33%) and CD8 + T-cell counts (4.17%) below normal ranges. Notably, elevated globulin and immunoglobulin (Ig) G were observed in over 50% of patients, while IgE was increased in 44% of cases. The oxygenation index was measured in 21 patients, with 4 patients demonstrating values below 300. Twelve patients showed weak-positive autoimmune antibodies, such as antinuclear antibodies, most of which were considered clinically insignificant.

Table 2.

Laboratory data in AIGA-positive patients with airway involvement

Variables	N (%)	Median [P25, P75] or mean ± SD	reference value
WBC×109 cells/L	27 (81.82) a	13.73 [11.08–19.21]	3.5–9.5
Neu×109 cells/L	27 (81.82) a	10.62 [7.50-15.22]	1.5–6.3
Lym×109 cells/L	5 (15.15) b	2.10 ± 0.88	1.1–3.2
Mon×109 cells/L	24 (72.73%) a	0.82 ± 0.35	0.1–0.6
Eos×109 cells/L	13 (39.39) a	0.33 [0.16–0.96]	0.02–0.52
PLT×109 cells/L	24 (72.73%) a	418.07 ± 100.42	125–350
HGB (g/L)	29 (87.88) b	106.72 ± 2.14	130–175(male) 115–150(female)
PCT (ng/mL)	5 (15.63) c*	0.159 [0.08–0.36]	0-0.05
CRP (mg/L)	30 (90.91) a	90.63 ± 5.56	0–10
ESR (mm)	28 (93.33) a*	77.20 ± 3.23	0–15
Serum ferritin(ng/mL)	18 (64.29) a*	497.34[200.45-1147.30]	21.8-274.66
Total T cells (%)	6 (22.22) b*	67.60 [62.84–71.53]	62.6–76.8
CD4 + T cells (/uL)	8 (33.33) b*	797.62 ± 285.53	561–1137
CD8 + T cells (/uL)	1 (4.17) b*	552.50 [300.25-902.75]	220–1030
B cells (%)	6 (33.33) b*	11.25 [7.31–18.86]	8.5–14.5
IgG (g/L)	21 (70.00) a*	22.48 [15.77–32.96]	8.6–17.4
IgA (g/L)	4 (13.33) a*	2.95 ± 1.08	1.0-4.2
IgM (g/L)	0 (0) a*	1.38 ± 0.58	0.5–2.8
IgE (IU/mL)	11 (44.00) a*	69.5 [34.05–252.90]	< 100
GLB (g/L)	21 (63.64) a	43.00 [36.10–49.70]	20–40
ALB (g/L)	31 (93.94) b	31.72 ± 5.69	40–55
ALT (U/L)	2 (6.06) a	15.00 [10.00–23.00]	15–40
CCR (ml/min)	13 (39.39) b	79.87 ± 21.05	75–115
OI	18 (85.71) b*	350.39 ± 53.69	400–500
SARD autoantibodies	12 (46.15)	-	negative

WBC white blood cell, Neu neutrophil, Lym lymphocyte, Mon monocyte, Eos eosinophil, PLT platelet, HGB hemoglobin, PCT procalcitonin, CRP C-reactive protein, ESR erythrocyte sedimentation rate, Ig immunoglobulin, GLB globulin, ALB albumin, ALT alanine aminotransferase, CCR creatinine clearance rate, OI oxygenation index, SARD autoantibodies systemic autoimmune rheumatic disease–associated autoantibodies

Superscripts: a = variables with elevated levels, b = variables with reduced levels, c = cases with procalcitonin > 0.5 ng/mL. * = data available for < 33 cases

Every included patient had involvement of at least two organs, specifically the lungs and airway. Apart from the lungs and airway, lymph nodes (93.94%) and bone (39.39%) were the most frequently involved organs. Mediastinal lymph nodes (93.94%) were the most commonly involved, followed by hilar lymph nodes (69.70%). Lymph node biopsy was performed in 20 patients, revealing granulomatous inflammation in 2 cases, fibrinous exudate in 4 cases, TM in 1 case, acid-fast positive bacteria in 1 case and Aspergillus in 1 case. The maximum number of involved organs was seven, including the lungs, airway, lymph nodes, spleen, blood, skin, and bone. The involvement of blood, spleen, liver, and skin occurred in a small number of patients. Next-generation sequencing (NGS) and blood culture confirmed bloodstream infections in four patients. NGS identified coinfections in two patients: [1] TM and Burkholderia vietnamiensis; [2] Stenotrophomonas maltophilia and Nocardia spp. Blood culture grew TM in one patient and Salmonella serogroup D in another.

Among the 33 patients, the rate of single pathogen infection and co-infection was 33.33% and 66.67%, respectively. The detected pathogens included TM (57.58%), NTM (42.42%), and other commonly reported opportunistic pathogens, as well as conventional pathogens found in patients without immunodeficiency diseases, such as Streptococcus pneumoniae, Haemophilus, Escherichia and so on (Table 3). Five patients had co-infections with TM and NTM, 23 patients were infected with one of these two pathogens, and the remaining 5 patients had infections caused by other pathogens. The majority of specimens used for pathogen detection were bronchoalveolar lavage fluid, with a small proportion from lung tissue, blood, lymph nodes, sputum, and bone. NGS served as the primary method for pathogen detection, with 27 samples testing positive. Moreover, a total of 13 patients yielded positive culture results. Of these cases, the species confirmed by culture were TM (n = 10), Salmonella serogroup D (n = 1), Pseudomonas aeruginosa (n = 1), Candida glabrata (n = 1), Aspergillus fumigatus (n = 1), and Aspergillus niger (n = 1). Additionally, 8 patients were diagnosed with NTM infections based on NGS findings: Mycobacterium avium (n = 4), Mycobacterium columbae (n = 3), Mycobacterium kansasii (n = 1), and Mycobacterium intracellulare (n = 1). Five patients were suspected to have NTM infections despite lacking pathogen evidence.

Table 3.

Diagnostic findings and therapeutic outcomes in AIGA-positive patients with airway involvement

Variables	Number	Percent (%)
Affected sites
Lung and airway	33	100%
Lymph node	31	93.94%
Bone	13	39.39%
Blood	4	12.12%
Spleen	4	12.12%
Liver	3	9.09%
Others (skin, pleura, pericardium, etc.)	5	15.15%
Pathogens
Talaromyces marneffei	19	57.58%
Nontuberculous mycobacteria	14	42.42%
Candida	5	15.15%
Aspergillus	1	3.03%
Mycobacterium tuberculosis	5	15.15%
Salmonella genus	1	3.03%
Burkholderia	1	3.03%
Conventional pathogens	27	Not applicable
Single pathogen infection	11	33.33%
Co-infection	22	66.67%
Diagnostic methods
Next generation sequencing	27	81.82%
Culture	13	39.39%
Clinical suspicion (NTM, TB)	7 (5, 2)	21.21%
Pathological diagnosis	2	6.06%
Acid-fast stain	2	6.06%
Chest CT findings
Mass	13	39.39%
Tracheobronchial stenosis	16	48.48%
Pulmonary nodule	17	51.52%
Consolidation	15	45.45%
Fibrotic bands	12	36.36%
Atelectasis	5	15.15%
Pleural effusion	13	39.39%
Cavity	2	6.06%
Bronchoscopy findings
Mass	14	42.42%
Nodule	10	30.30%
Tracheobronchial stenosis	16	48.48%
Mucosal hyperplasia/hypertrophy	13	39.39%
Mucosa congestion and edema	20	60.61%
Bleeding	2	6.06%
Discharge	20	60.61%
Treatment
Anti-NTM treatment	14	42.42%
Anti-TM treatment	18	54.54%
Regimen targeting conventional pathogens	16	48.48%
Oxygen therapy	19	57.58%
Adverse reactions	10	30.30%
Liver and kidney function abnormalities	5	15.15%
Elevated blood drug concentrations	4	12.12%
Gastrointestinal reactions	1	3.03%
Hearing loss	1	3.03%
Outcomes
Clinical improvement	26	78.79%
Acute exacerbation requiring readmission	3	9.09%
Loss to follow-up	4	12.12%

Chest CT imaging, bronchoscopic visualization, and tissue histology

The lung lesions, as visualized on CT scanning, were observed on either one side (30.30%) or both sides (69.70%) of the lungs and exhibited a variety of imaging appearances. These imaging appearances included masses (39.39%), tracheobronchial stenosis (48.48%), pulmonary nodules (51.52%), consolidation (45.45%), fibrotic bands (36.36%), atelectasis (15.15%), pleural effusion (39.39%), cavities (6.06%), and others. Typical images were selected and presented in Fig. 1. All patients underwent bronchoscopy. The bronchoscopic diagnoses were reported by endoscopists. Masses (42.42%), nodules (30.30%), and tracheobronchial stenosis (48.48%) were visualized in a subset of cases during bronchoscopy, which are the predominant direct suggestions of airway involvement. Masses typically present as larger lesions with irregular surfaces and broad bases, and may cause significant airway obstruction. Nodules manifest as localized mucosal protrusions characterized by smaller size, smooth surfaces, and narrow bases; they rarely cause luminal obstruction. Additional findings included mucosal hyperplasia/hypertrophy, mucosal congestion and edema, bleeding, and discharge that was purulent, serous, or caseous, or contained necrotic material. Figure 2 provides representative images captured during bronchoscopy. Twenty-three patients underwent bronchoscopic mucosal or mass biopsy, yielding 14 cases of chronic inflammation, 3 cases of acute and chronic inflammation, 5 cases of chronic purulent inflammation, and 1 case of granulation tissue. Of these, three samples showed granulation tissue hyperplasia or granuloma formation, while abscess formation was observed in two samples (Fig. 3).

Fig. 1.

A, B semicircular mass shadow (blue arrow) in the right main bronchus and luminal stenosis caused by the mass; C, D left lower lobe consolidation, an irregular mass in the left main bronchus (blue arrow), and bilateral pleural effusion; E luminal stenosis of the right intermediate bronchus (blue arrow) and consolidation in the right middle lobe; F A nodule with pleural retraction in the lower right lobe; G, H A mass in the right hilum

Fig. 2.

A A fish-flesh-like neoplasm in the right main bronchus, corresponding to the Fig. 1A; B Purulent and hemorrhagic components in the apical segment of the right upper lobe; C Expiratory-phase airway collapse; D A neoplasm near the bronchus intermedius-lower lobe junction with luminal swelling; E A bleeding-prone mucosal nodule at the orifice of the basal segmental bronchus in the left lower lobe; F A nodular neoplasm at the orifice of the right upper lobe bronchus, G A captured image of neoplasm shown in Fig. 2 F from a closer distance; H Mucosal hyperplasia/hypertrophy in the right middle bronchus

Fig. 3.

A Acute and chronic inflammation of bronchial mucosa with hemosiderin deposition; B Chronic suppurative inflammation of a bronchial mass accompanied by granuloma formation (red arrow); C Acute and chronic inflammation of bronchial mucosa with focal abscess formation (red arrow)

Treatments and outcomes

Targeted pathogen-specific therapy was initiated during hospitalization. A total of 18 patients received anti-TM therapy, and 14 received anti-NTM therapy. Detailed regimens and treatment durations for both NTM and TM infections are provided in Supplementary Table 1. Broad-spectrum antibiotics were added for 16 patients due to detection of conventional pathogens. Of the four patients with bloodstream infections, only the one with Salmonella infection developed septic shock. This patient’s condition did not necessitate intensive care during hospitalization. A total of 19 patients received oxygen therapy. The efficacy and safety of the treatment for all patients were evaluated during the first month after discharge. During this period, 26 patients achieved clinical improvement, 3 experienced acute exacerbation requiring readmission, and 4 were lost to follow-up. Adverse events related to the therapeutic drug were reported in 10 patients, including abnormal liver and kidney function, elevated blood drug concentrations, and gastrointestinal reactions (Table 3). These events were mild and not life-threatening, but required discontinuation or adjustment of the regimens.

Discussion

Previous reports have described the clinical features of organ involvement in patients with AIGA-related immunodeficiency syndrome, but airway involvement is extremely rare. Thus, we collected and analyzed the clinical information from this subset of patients to fill the knowledge gap. In this study, we enrolled 33 patients who were identified as having airway involvement via bronchoscopy or chest CT. Since inhalation of T. marneffei spores from the environment may lead to infection [8], contact with bamboo rats might be a potential risk factor for immunocompromised patients. Only three patients had definite exposure to bamboo rats, and two of them developed TM infection. Although TM is one of the most common pathogens in AIGA-positive patients, the prevalence of bamboo rat exposure in this population remains unexplored. Ethnic composition is rarely reported in existing studies. In our cohort, the Zhuang ethnic group constituted 51.52% of the patients, followed closely by the Han group at 45.45%. Although the Han ethnicity is the majority population in Guangxi, disease prevalence was higher in the Zhuang group. Whether this disparity relates to specific genetic factors remains to be elucidated. For genetic susceptibility, the HLA-DRB1*16:02 and HLA-DQB1*05:02 alleles have been reported to be more frequent in AIGA-positive patients than in healthy subjects [5, 9].

AIGA-related immunodeficiency syndrome is categorized into infectious and non-infectious diseases. Elevated inflammatory parameters and pathogens detected in various samples indicated infectious diseases in the included patients. Laboratory data showed that CD4 + and CD8 + T-cell counts were rarely decreased, suggesting that functional impairment of T lymphocytes, rather than numerical deficiency, is likely responsible for the susceptibility to opportunistic infections in AIGA-positive patients. Elevated levels of immunoglobulins (specifically IgG and IgE) and AIGAs, all produced by plasma cells, suggest immune dysfunction related to B cells. NTM-infected patients with AIGAs had higher levels of antibody-enhancing B cell subsets, including transitional (IgM + + CD38++), CD19 + CD21-low, and plasmablasts, than both NTM-infected, AIGA-negative patients and healthy controls [10].

The predominant pathogens were TM and NTM based on our findings, which is consistent with previous research [11]. Moreover, the pathogens detected in our study also included other conventional, non-opportunistic pathogens, such as Streptococcus pneumoniae, Escherichia spp., and Enterobacter spp., occurring in patients without high risk factors for immunodeficiency. These conventional infections have not been reported in recent years. One of the four patients with bloodstream infections developed septic shock; however, whether the AIGA-related bloodstream infections are associated with a milder clinical phenotype remains uncertain and requires validation in larger cohorts.

Masses, nodules, and tracheobronchial stenosis were significant findings observed via bronchoscopy, directly indicating airway involvement. These changes in the airways were associated with a reduction in oxygenation index and necessitated oxygen administration. However, none of the patients required non-invasive or invasive ventilation support. Although some CT imaging and bronchoscopic findings raised suspicion for malignant tumors, all pathological results offered no evidence of malignancy. The effort to obtain pathogens and pathological results helps clinicians exclude malignancy and make the correct diagnosis. Previous case reports have described the skin and eyes as affected organs in non-infectious disease, which commonly responds well to glucocorticoids [12–14]. The pathological results of airway tissues in our study revealed infectious lesions, without non-infectious findings. As reported in lymph node biopsies, the predominant pathological pattern of tracheobronchial lesions was inflammation with or without granuloma formation [15]. Clinicians should maintain vigilance for infections caused by opportunistic pathogens and test for AIGAs when pathological findings show chronic inflammation with granuloma formation.

Patients received targeted pathogen-specific therapy, and the majority achieved clinical improvement in this study. As is known, infections caused by TM and NTM require long-term antimicrobial therapy. Hence, the efficacy and safety of such therapy are the primary concern for clinicians. Our data showed that 78.79% of patients benefited from treatment and about one-third of patients experienced drug-related adverse reactions during the first month after discharge, highlighting the importance of close monitoring for adverse effects. Pei et al. demonstrated that long-term erythromycin treatment reduces airway and gut microbial abundance in COPD patients without affecting diversity but reshapes microbial community composition by reducing pathogenic bacterial abundance [16]. Thus, further studies examining how prolonged antimicrobial exposure alters airway and gut microbiota in AIGA-positive patients receiving continuous anti-NTM treatment for > 1 year could provide mechanistic insights into the long-term effects of antimicrobial agents.

It should be acknowledged that our study has certain limitations. First, it is a retrospective study, and some laboratory examinations were not conducted. Moreover, limited specimen availability from endobronchial mucosal biopsies led to incomplete pathological datasets. Finally, long-term follow-up data are lacking.

Conclusions

Tracheobronchial infections are part of the spectrum of systemic manifestations in patients with AIGAs and may be easily overlooked. We summarized their clinical characteristics in 33 patients, which may enhance clinicians’ understanding and reduce misdiagnosis as tumors.

Abbreviations

IFN

Interferon

AIGAs

Anti-interferon-γ autoantibodies

NTM

Nontuberculous mycobacteria

TM

Talaromyces marneffei

CT

Computed tomography

ELISA

Enzyme-linked immunosorbent assay

COPD

Chronic obstructive pulmonary disease

Ig

Immunoglobulin

NGS

Next-generation sequencing

Authors’ contributions

Zhiyi He conceptualized and designed the study. Siyao Wu, Yan Ning, Haiyan Pang, Ziyi Zhang, Ni Chen, and Limei Hong collected clinical data and followed up the patients. Xuemei Huang and Hanlin Liang conducted the experiments. Nan Ma performed statistical analyses. Xiaona Liang and Siqiao Liang wrote the draft manuscript. All authors critically revised and approved the final manuscript.

Funding

This work was supported by the National Key R&D Program of China [grant no.2024YFC2309600]; Guangxi Science and Technology Program [grant no.2023AB22055]; and Central Leading Local Science and Technology Development Fund Project [grant no.2023ZYZX1021].

Data availability

The data that support the findings of this study are not openly available due to patient privacy restrictions. De-identified data may be made available to qualified researchers upon reasonable request, subject to approval by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and execution of a formal data sharing agreement. Requests should be directed to the corresponding author or the hospital ethics committee.

Declarations

Ethics approval and consent to participate

The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval no. KY-E-2019-038; approval no. KY-E-2020-173). This study was conducted in accordance with the Declaration of Helsinki and relevant national guidelines and regulations. Clinical trial number: not applicable. Written informed consent was obtained from all participants.

Consent for publication

Written informed consent was obtained from patients for publication and the accompanying images.

Competing interests

The authors declare no competing interests.