Background:Anti-interferon-γ autoantibodies (AIGAs) immunodeficiency syndrome is an emerging adult-onset immunodeficiency causing opportunistic infections. However, its comprehensive immune landscape remains elusive. This study presents the first single-cell RNA sequencing (scRNA-seq) analysis of AIGAs immunodeficiency syndrome, aiming to delineate its pathogenic mechanisms. Methods:We performed scRNA-seq on peripheral blood mononuclear cells (PBMCs) from 8 AIGAs immunodeficiency syndrome patients (4 infective, 4 stable phase) and 3 healthy controls. Findings were validated by flow cytometry in an expanded cohort (15 patients vs. 10 controls). Results:Single-cell RNA sequencing of PBMCs from patients with AIGAs immunodeficiency syndrome identified a comprehensive immune subset profile, including effector memory CD4+ T cells, naive CD4+ T cells, regulatory T cells, GNLY+ CD8+ Tem, GZMK+ CD8+ Tem, naive CD8+ T cells, naive B cells, memory B cells, plasma cells, ISG+ atypical B cells, monocytes, and NKT cells. ScRNA-seq analysis revealed a significantly higher proportion of Th1 cells (16.62% vs. 6.94% in controls) and ISG+ B cells (2.95% vs. 0.53%), alongside a lower proportion of plasma cells (9.30% vs. 17.79%) and memory B cells (9.54% vs. 27.35%). Flow cytometry consistently confirmed the increase in Th1 cells (21.84% [14.87-27.57] vs. 11.96% [7.19-15.74]) and decreases in marginal zone B cells (2.87% [1.71-4.45] vs. 8.60% [6.77-15.65]), memory B cells (13.85% [5.72-20.23] vs. 22.96% [16.39-33.83]), and class-switched B cells (6.11% [2.39-9.10] vs. 10.18% [5.35-15.77]). Transcriptome analysis demonstrated upregulated expression of interferon-response and HLA genes (e.g., HLA-DQB1, HLA-DQA1, HLA-DRB1), whereas IRF1 was downregulated across all subsets; functional enrichment analyses further highlighted significant activation in IFN signaling and B cell activation pathways. CellChat and pseudotime analyses indicated that CD4+ Tem and CD14+ monocytes drive sustained Th1 inflammation and monocyte hyperactivation through enhanced pro-inflammatory and antigen-presenting interactions, with T-cell differentiation skewed toward terminal effectors and B-cell development disrupted by ISG+ B cell emergence, premature plasma cell formation, and IGLC3-biased class switching, collectively delineating the interferon-mediated immunopathology of AIGAs immunodeficiency syndrome. Conclusions:In summary, this first single-cell atlas maps AIGAs immunodeficiency syndrome as a Th1-skewed, IFN-γ-driven disorder sustained by CD4+ Tem-CD14+ monocyte crosstalk. It combines T-cell activation, expanded Th1 and ISG+ B cells, and loss of memory/plasma B cells to drive autoantibody generation. Skewed T- and B-cell trajectories and polygenic up-regulation of interferon/HLA genes provide a clear mechanistic rationale for targeted therapy.

BackgroundAnti–interferon-γ autoantibodies (AIGAs) are an established cause of adult-onset immunodeficiency (AOID), predisposing individuals to disseminated intracellular infections such as Talaromyces marneffei (TM). However, their role in promoting persistent immune dysregulation and subsequent lymphomagenesis remains poorly understood.Case presentationA 63-year-old Chinese female with high-titer AIGAs (1:2500) initially presented with disseminated TM. Despite antifungal therapy, her clinical course was complicated by recurrent opportunistic infections—including Varicella-zoster virus (VZV) and Mycobacterium persicum (M. persicum), and steroid-dependent inflammatory episodes. Approximately two years after the initial presentation, she developed an Epstein-Barr virus (EBV)-positive aggressive B-cell lymphoma, confirmed by mass biopsy and PET/CT. Despite treatment with rituximab and broad-spectrum antimicrobials, she died of Gram-negative septic shock. Whole-exome sequencing (WES) revealed a CREBBP p.Q278P mutation, providing a genetic perspective on her disease susceptibility.ConclusionThis case illustrates a rare progression from AIGAs-associated immunodeficiency to EBV-driven lymphoma, suggesting a “triple-hit” pathogenic model that warrants further investigation, comprising: (1) AIGAs-associated AOID; (2) chronic antigenic stimulation from persistent infections that may exacerbate immune dysregulation; and (3) a CREBBP mutation that may act as a genetic contributor to malignant transformation. This case underscores the necessity for rigorous tumor surveillance and individualized treatment in patients with AIGAs-associated immunodeficiency.

Background The use of solid fuels for cooking is a significant public health concern, especially for middle‐aged and older adults. Limited longitudinal data exists on the impact of transitioning to clean fuels on cardiopulmonary health. Methods Data from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2020) were analyzed. From the baseline solid fuel users, we constructed two independent subcohorts to evaluate short‐term (2013–2015) physiological changes and long‐term (through 2020) disease risks, respectively. Multivariable regression models assessed short‐term changes in peak expiratory flow (PEF), blood pressure, and pulse and long‐term risks of cardiopulmonary diseases. Results Among the 6534 participants in the short‐term cohort, 27.4% transitioned to clean cooking fuels by 2013. The transition to clean fuels was associated with a significant attenuation of PEF decline by 11.0 L/min (95% CI: 4.7–17.3; p < 0.001), which was partially mediated by reductions in depressive symptoms (mediating proportion = 12 % ). A modest but significant reduction in systolic blood pressure was also observed ( β = −1.7, p = 0.017). In the long‐term cohort ( n = 6362), with 33.5% transitioning by 2015, clean fuel use was associated with a 20% lower risk of chronic lung disease (OR = 0.80, 95% CI: 0.7–1.0, p = 0.044) and heart disease (OR = 0.80, 95% CI: 0.7–1.0, p = 0.028) but no significant association with hypertension. Protective effects were more pronounced in nonsmokers and nondrinkers (OR range: 0.7–0.8). Conclusion Transition to clean cooking fuels is associated with slower pulmonary decline and lower cardiopulmonary disease risk, supporting its role in healthy aging strategies.

Purpose Anti-interferon-γ autoantibodies (AIGAs)-associated immunodeficiency is a rare, adult-onset disorder characterized by multi-system infections with geographic variability. However, the clinical features and prognosis related to skeletal involvement remain unclear. Methods A 10-year retrospective study of AIGAs-positive skeletal involvement with HIV-negative patients from Guangxi, China. Results A total of 103 patients (median onset age: 55 years; median follow-up: 28.40 months), hypertension (29.13%) and HBV carriage (10.68%) were prevalent underlying diseases. Cough/sputum (66.99%) was the predominant initial symptom, while bone pain (21.36%) was less common. Among those with bone involvement, peripheral lymphadenopathy (86.41%) and cough/sputum (85.44%) were highly prevalent, unlike bone/joint pain (37.86%) and myalgia (14.56%). Most patients exhibited elevated levels of white blood cells, neutrophils, C-reactive protein, procalcitonin, erythrocyte sedimentation rate, globulin, immunoglobulin (Ig) G, and IgE. The predominant types of infection were disseminated Talaromyces marneffei (TM) (63.11%) and non-tuberculous mycobacteria (NTM) (55.34%), with an increasing trend of co-infection observed. Chest CT revealed lung involvement in all patients, with 63.11% exhibiting bone lesions. Bone emission computed tomography (ECT) showed abnormal uptake in the thoracic (75.73%) and lumbar vertebrae (56.31%); 63.11% of patients had bone destruction, of which 13.59% were osteolytic. All patients received full-course anti-infective therapy, some received individualized immunotherapy, and 19.41% required surgical intervention. Conclusion Skeletal involvement in AIGAs syndrome is common yet occult, presenting as disseminated infection, with TM and NTM co-infection complicating the course. The axial skeleton is frequently involved, with early detection by skeletal ECT enabling comprehensive treatment and precise management to improve prognosis.

Background:Anti-interferon-γ autoantibodies (AIGAs) immunodeficiency syndrome is a rare acquired disorder characterized by impaired IFN-γ signaling, predisposing patients to severe intracellular infections. While disseminated non-tuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) are well-documented pathogens, the clinical and immunological features of Salmonella coinfection remain poorly characterized. Methods:This retrospective study analyzed 12 HIV-negative patients with AIGAs-positive status and confirmed Salmonella infection at the First Affiliated Hospital of Guangxi Medical University, China (2021-2024). Data included demographics, clinical manifestations, laboratory findings, co-infections, treatment, and outcomes. AIGAs were detected via ELISA and Western blot, with neutralizing activity confirmed by STAT1 phosphorylation inhibition. Results:The cohort was predominantly composed of middle-aged males (83.3%, mean age 55.75 ±8.06 years). The most common symptoms were fever, fatigue and cough (each 91.7%), followed by poor appetite (83.3%), systemic symptoms (chills, weight loss; 58.3%) and dyspnea (58.3%). Bone or joint pain occurred in 41.7% and gastrointestinal complaints (abdominal pain, diarrhea or distension) in 25%. Five patients (41.7%) developed septic shock, three requiring vasopressors and two mechanical ventilations. All had high AIGAs titres (1:2500) and hyper-inflammation (median WBC17.3×109/L, CRP138.1mg/dL, PCT1.28ng/mL). Bacteraemia was present in 91.7% and mortality was 16.7% (2/12). Polymicrobial co-infection was universal; notably cytomegalovirus (50%) and TM (25%). Immunological profiling showed hyperglobulinaemia (IgG23.5±10.6g/L) and elevated IgE (257.5[79.7-598.2]IU/mL). Despite broad-spectrum antibiotics (83.3% survival), both fatalities occurred in patients who had not undergone NGS-based diagnosis. Conclusion:This study is the first to define AIGAs-associated Salmonella infection as a distinct clinical syndrome, characterized by severe bacteremia, paradoxical hyperinflammation, universal polymicrobial coinfections, and immune dysregulation. Our findings underscore the critical importance of comprehensive pathogen detection, particularly via NGS, for timely diagnosis and improved patient outcomes.

Adult-onset immunodeficiency syndrome mediated by anti-interferon-gamma autoantibody (AIGA) is a rare disorder that has garnered increasing recognition in recent years. The condition is most prevalent among adults in Southeast Asia. It is characterized by recurrent disseminated opportunistic infections, frequently involving multiple organ systems such as the lungs, lymph nodes, bones, and skin. The pathogenesis is primarily attributed to the presence of neutralizing AIGAs, which impair the IFN-γ–mediated JAK–STAT1 signaling pathway, leading to compromised host defense against intracellular pathogens. Laboratory diagnosis requires both quantification of AIGA titers and assessment of their neutralizing activity. Clinical diagnosis relies on a combination of characteristic manifestations, demonstrated immunologic dysfunction, and seropositivity for AIGAs. During the acute stage, management focuses on antimicrobial therapy, while during the stable stage, it can be categorized into three clinical subtypes: high AIGA titers with immune damage, high AIGA titers without immune damage, and low AIGA titers without immune damage. Among these, patients with high AIGA titers and immune damage require immunomodulatory strategies—such as glucocorticoids and rituximab—tailored to individual AIGA levels and immune status. Due to the current absence of unified clinical guidelines, this review synthesizes available evidence and clinical expertise to provide a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnostic criteria, and treatment approaches related to AIGA-mediated immunodeficiency. Our aim is to assist clinicians in the recognition and management of this syndrome and to facilitate further clinical research and guideline development.

BackgroundAnti-interferon-gamma (IFN-γ) autoantibodies (AIGAs) syndrome is an emerging adult-onset immunodeficiency (AOID) associated with opportunistic infections and immune dysregulation. Pericardial effusion as a direct manifestation of this syndrome is rarely reported.Case presentationA 46-year-old man with a history of Talaromyces marneffei (TM) infection and clinically suspected pulmonary nontuberculous mycobacterial (NTM) disease presented with rapid-onset massive pericardial effusion. The NTM diagnosis was not microbiologically confirmed, as the patient declined bronchoscopy. Pericardial fluid analysis revealed a high inflammatory cell count and an anti-IFN-γ autoantibody titer of 1:2500, identical to serum, despite a negative microbiological workup and no definitive evidence of malignancy on available cytological evaluation. The patient responded well to corticosteroids and anti-NTM therapy, with complete resolution of effusion.ConclusionThis case highlights pericardial effusion as a potential immune-mediated complication of AIGAs syndrome. Clinicians should consider this diagnosis in patients with unexplained serositis and a history of opportunistic infections.

BackgroundThe etiology of neck masses is complex. Infections caused by Talaromyces marneffei (TM) and nontuberculous mycobacteria (NTM) are uncommon but often present with insidious clinical manifestations, leading to frequent misdiagnosis.MethodsWe collected and analyzed data from 13 patients with TM/NTM infections presenting with neck masses at The First Affiliated Hospital of Guangxi Medical University and The Second Affiliated Hospital of Guangxi Medical University. Clinical manifestations, laboratory findings, infection sites, pathogen types, treatments, and outcomes were described and analyzed.ResultsOf the 13 patients, six were male and seven female, with a median age of 57 years (range, 27–73 years). All patients were residents of Guangxi and tested positive for anti-interferon-γ autoantibodies (AIGAs), with titers of 1:2500 in 12 patients and 1:500 in one. The median time from symptom onset to diagnosis was 5 months (range, 1–19 months). Common clinical features included lymphadenopathy (13/13), fever (11/13), respiratory symptoms (10/13), and rash or skin ulceration (8/13). Frequent laboratory abnormalities included leukocytosis (11/13), neutrophilia (11/13), elevated erythrocyte sedimentation rate (12/13), and elevated C-reactive protein (13/13). Coinfection with two or more pathogens was observed in 12 patients. The lungs and lymph nodes were involved in all 13 patients, followed by bone (11/13), skin or soft tissue (8/13), bloodstream or bone marrow (3/13), and nasopharynx (3/13). Neck mass specimens yielded NTM in nine cases and TM in four. NTM was most frequently identified by metagenomic next-generation sequencing (mNGS), whereas TM was detected by culture. The median follow-up duration was 28 months (range, 1–86 months). During follow-up, 6 patients (46.2%) experienced disease exacerbations. Among the 13 patients, 12 achieved clinical improvement after pathogen-directed antimicrobial therapy, while one patient died.ConclusionNeck masses have diverse etiologies. TM and NTM infections presenting initially as neck masses are rare and easily misdiagnosed as tuberculosis, malignancy, or lymphoma. Culture and mNGS are crucial diagnostic tools for TM and NTM, respectively. Clinicians should maintain a high index of suspicion for these infections, particularly in immunocompromised patients in endemic regions.

Background: Type 2 diabetes mellitus (T2DM) patients infected with coronavirus disease 2019 (COVID-19) are at a higher risk of experiencing poorer prognoses and increased mortality. Glucocorticoids are recommended for the treatment of COVID-19, especially in patients with severe disease. However, the efficacy and safety of glucocorticoids in COVID-19 patients with T2DM remain a subject of debate. Methods: We conducted a multicenter, retrospective cohort study of hospitalized patients with T2DM and confirmed COVID-19 admitted between November 1, 2022 and January 31, 2023. Data on clinical manifestations, treatment strategies, and clinical outcomes were systematically collected and rigorously evaluated. Results: A total of 624 COVID-19 patients with T2DM were enrolled, comprising 259 patients with severe disease and 365 with non-severe disease. Compared with the non-severe group, the severe group demonstrated significantly elevated levels of inflammatory markers and more extensive multi-organ dysfunction. Multivariate logistic regression identified advanced age, male sex, cerebrovascular disease history, and poor fasting glucose control as independent predictors of progression to severe illness. Among patients with severe disease, glucocorticoid therapy was significantly associated with reduced in-hospital mortality and a shorter median length of stay; this association remained robust after adjustment for baseline glycemic status. Six-month post-discharge follow-up revealed no significant between-group differences in the incidence of long COVID-19 or interstitial pneumonia; however, among patients in non-severe group, those who received glucocorticoids exhibited a higher incidence of long COVID-19. Conclusion: Glucose control is of particular importance for COVID-19 patients with T2DM. In mild or moderate cases, systemic use of glucocorticoid therapy should be strictly evaluated. In severe or critical cases, cautious, appropriate use of glucocorticoids may be associated with improved short-term prognosis and reduced mortality.

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. 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. 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

Nontuberculous mycobacterial infectious diseases are associated with host immunological status. Neutralizing anti-interferon (IFN)-γ autoantibodies have been considered as a significant cause of nontuberculous mycobacterial infections. However, another autoantibody specifically targeting interferon-α, occurring in patients with nontuberculous mycobacterial infection, has been rarely reported. We report the case of a 23-year-old female who developed refractory nontuberculous mycobacterial infection and subsequently manifested skin lesions and motor disorder of muscles. The laboratory examination results showed elevated levels of globulin and immunoglobulin, as well as local deposits of amyloid material in pleural sections. Additionally, various tissue biopsies showed no evidence of malignancy. After 6 months of anti-nontuberculous mycobacterial therapy, the patient recovered normal temperature but developed progressive pulmonary lesions. The patient received steroids and methotrexate treatment and her skin lesions as well limitation of muscle movement improved. Further evaluation revealed a hidden immunodeficiency with positive anti-interferon-α autoantibodies and recombinase activating gene (RAG) mutation. This case highlights alternation of infection and immune dysregulation, likely resulting from RAG mutation and production of anti-interferon-α autoantibodies.

Anti-interferon-γ autoantibodies (AIGAs) syndrome is a recently recognized adult-onset immunodeficiency syndrome. Serum Immunoglobulin E (IgE) is increased in AIGAs syndrome, but the role of serum IgE levels in the clinical features and disease outcomes of AIGAs syndrome is not clear. We retrospectively enrolled 163 patients diagnosed AIGAs syndrome with serum IgE examined at baseline from 2021 to 2024 and compared the clinical features between Group A (serum IgE level ≤ 212 IU/mL) and Group B (serum IgE level > 212 IU/mL). Multivariable logistic regression method was used to explore the risk factors associated with disease outcomes. 163 patients were included in this study, of whom 97 patients were in Group A (serum IgE level ≤ 212 IU/mL) and 66 patients in Group B (serum IgE level > 212 IU/mL). Group B showed higher number of infectious episodes, elevated levels of erythrocyte sedimentation rate (ESR), CD3 + T cells, immunoglobulin G (IgG), IgA, and globulins (GLB), shorter progression-free survival (PFS), and increased exacerbation numbers. Group B exhibited a higher incidence of fatigue, dyspnea, loss of appetite, rash, moist rales, hepatomegaly, and splenomegaly. Skin, bone marrow and spleen involvements were more common in Group B. IgE demonstrated correlations with IgG, GLB, Albumin (ALB), Eosinophils (EOS), IgG4, and ESR. During the follow-up, Group B exhibiting higher number of exacerbations compared to Group A (P < 0.0001). Multivariable Cox regression analysis revealed that High AIGAs titers (hazard ratio [HR], 2.418, 95

Skin cutaneous melanoma (SKCM) is a cancer with serious global impact. Long non-coding RNA was previously found to be associated with tumor prognosis. This research focuses on long intergenic non-protein coding (LINC) RNAs, and correlated protein-coding genes (PCGs), to explore their diagnostic and prognostic value, function and mechanism. Gene expression data was obtained from TCGA and Oncomine for analysis; in total there were 458 cases included in this study. LIN00518 and the 10 most highly correlated PCGs were selected to determine the diagnostic and prognostic value. We undertook bioinformatic analysis with LINC00518 and the prognostic-related PCGs in order to explore their molecular mechanism. The Connectivity Map was carried out for pharmacological target prediction and drug selection. Among the top 10 correlated PCGs, trafficking kinesin protein 2 (TRAK2), epilepsy of progressive myoclonus type 2 gene A (EPM2A) and melanocyte inducing transcription factor (MITF) had significant diagnostic value (all AUC > 0.7, P < 0.05). LINC00518, ras association domain family member 3 (RASSF3), cdk5 and Abl enzyme substrate 1 (CABLES1), kazrin, periplakin interacting protein (KAZN), EF-hand calcium binding domain 5 (EFCAB5) and MITF were significantly associated with prognosis (all adjusted P < 0.05). LINC00518 was associated with cell cycle process, melanogenesis, MAPK signaling pathway, cell division and DNA repair(all P < 0.05). Pharmacological targets analysis suggested results acquired eight potential target drugs. Up-regulation of LINC00518 is significantly associated with poor prognosis. TRAK2, EPM2A and MITF had diagnostic significance. RASSF3, CABLES1, KAZN, EFCAB5 and MITF had prognostic significance. This study provided novel biomarkers for SKCM.

IntroductionAnti-interferon-γ autoantibodies (AIGAs) syndrome is a rare, adult-onset immunodeficiency characterized by increased susceptibility to various opportunistic infections. Currently, there are no standardized diagnostic or therapeutic guidelines for AIGAs syndrome, making clinical management challenging.GoalsTo summarize and synthesize the published literature on the demographic characteristics, infection types, affected organs, treatments, and outcomes of AIGAs syndrome. This review aims to provide a comprehensive summary of current knowledge regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of AIGAs syndrome.MethodsWe searched PubMed, EMBASE for publications in English between January 1, 2004, and March 8, 2025 relating to AIGAs syndrome. Data from eligible studies were extracted and synthesized to summarize demographic characteristics, infection types, affected organs, treatments, and outcomes.ResultsA total of 149 eligible studies, encompassing 1430 patients (664 males [46.43%], 672 females [46.99%], and 94 with unmentioned gender), were included. Patients frequently presented with two or more opportunistic infections, most commonly non-tuberculous mycobacteria (NTM, 55.69%), Talaromyces marneffei (TM, 26.98%), Salmonella spp. (12.43%), Mycobacterium tuberculosis (9.34%), and varicella-zoster virus (VZV, 9.57%). Multi-organ involvement was common, particularly affecting lymph nodes (70.24%), lungs (58.75%), bones/joints (38.89%), and skin (45.16%). Clinical outcomes included remission (45.08%), persistent (15.98%), relapse (21.62%), and death (11.68%). In addition to anti-infective therapy, corticosteroids, rituximab, and cyclophosphamide were commonly employed as immunotherapies.ConclusionsAIGAs syndrome is associated with diverse opportunistic infections, particularly NTM, TM, Salmonella, Mycobacterium tuberculosis, and VZV. Multi-organ and multi-system involvement is frequent, with a tendency toward persistent or relapsing disease and associated mortality. Corticosteroids may represent the most promising immunomodulatory therapy in the future.

Patients with positive anti-IFN-γ autoantibodies (AIGAs) are characterized by susceptibility to disseminated infection by multiple pathogens. The clinical characteristics of non-tuberculous mycobacterial (NTM) infection with AIGAs positivity remain unclear. A prospective cohort study was conducted at the First Affiliated Hospital of Guangxi Medical University from January 2021 to January 2024. A total of 93 patients diagnosed with NTM infection were divided into two groups: AIGAs-positive with NTM infection and AIGAs-negative with NTM infection. The clinical manifestations, laboratory data, imaging examination, and pathogens were analyzed to characterize the disease. A total of 44 AIGAs-positive and 49 AIGAs-negative patients with NTM infection were enrolled. Disseminated infections were significantly more common among AIGAs-positive patients (P < 0.001), with frequent co-infections involving Talaromyces marneffei (TM) and viruses. Additionally, AIGAs-positive patients exhibited elevated inflammatory markers and immunoglobulins. In the AIGAs-positive group, lymph nodes, bones, skin, and blood were the most frequently affected sites. Chest CT scans exhibited a range of findings. Over a mean follow-up period of 36 months, 56.82

Anti-interferon-γ autoantibodies syndrome (AIGAs syndrome) is characterized by disseminated infections involving various pathogens. The clinical manifestations of AIGAs syndrome with Talaromyces marneffei (TM) infection are not yet completely understood. A prospective cohort study was conducted at the First Affiliated Hospital of Guangxi Medical University from January 2021 to February 2024. Patients diagnosed with TM infection were categorized into two groups: AIGAs-positive with TM infection group (Group 1) and AIGAs-negative with TM infection group (Group 2). We analyzed the clinical manifestations, laboratory data, imaging findings, and pathological characteristics of the patients to gain insights into the disease’s clinical features. A total of 80 AIGAs-positive patients with TM infection (Group 1) and 23 AIGAs-negative patients with TM infection (Group 2) were enrolled. Disseminated infection was significantly more common among Group 1 patients (P < 0.001). Patients in Group 1 had higher serum G test levels than those in Group 2 (P < 0.001). They also showed higher levels of white blood cells, neutrophils, lymphocytes, eosinophils, monocytes, C-reactive protein, erythrocyte sedimentation rate, serum ferritin, globulin, immunoglobulin (Ig)G, IgE, and IgG4 (P < 0.05). Common infection sites included the lungs, lymph nodes, bones, skin, and blood in Group 1 patients. Coinfections were frequently with cytomegalovirus (CMV) and non-tuberculous mycobacteria (NTM). Among patients with bone involvement, 92.6

BACKGROUND:Anti-interferon-γ autoantibodies (AIGAs) syndrome is a rare adult-onset immunodeficiency (AOID) syndrome with multiple opportunistic infections. However, its clinical characteristics in Mycobacterium tuberculosis (MTB) infection remain unclear. METHODS:A prospective cohort study of adult patients with opportunistic infections was conducted from January 2021 to January 2025 in Guangxi, southern China. MTB-infected patients were divided into AIGAs-positive and AIGAs-negative groups, and their clinical and laboratory data were compared. Additionally, the AIGAs-positive group was divided into subgroups (with or without nontuberculous mycobacteria (NTM) or Talaromyces marneffei (TM) co-infection) for detailed analysis. RESULTS:Among over 400 patients recruited, 48 of the 86 with MTB infection were AIGAs-positive (Group 1), and 38 were AIGAs-negative (Group 2). Group 1 patients commonly show involvement of the lungs, lymph nodes, bones, and skin, with often multi-organ involvement. Disseminated infections are more prevalent in Group 1, often accompanied by TM/NTM infections. They also show elevated white blood cell count, neutrophils, monocytes, C-reactive protein, erythrocyte sedimentation rate, globulin, and immunoglobulin G levels (P < 0.05). During an average follow-up of 19 months, 50.00 % of patients experienced acute exacerbations, of which 82.61 % were caused by new pathogen infections. Multivariable Cox regression analysis indicated that splenic involvement, elevated serum G test levels, and NTM infection were risk factors for disease progression (P < 0.05). The TM/NTM co-infected subgroup had higher acute exacerbation rates, AIGAs titers, inflammatory/immune markers, and more organ involvement. CONCLUSIONS:Patients with AIGAs-related AOID and MTB infection had high infection markers, immune issues, and multi-organ involvement, which worsened with TM/NTM co-infection.

Recently, increased reports reveal that anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs) are strongly associated with several severe disseminated infections. However, reports on AIGAs with central nervous system (CNS) infections are rare. Here, we described three AIGAs-positive adults who had persistent or recurrent disseminated infections caused by Talaromyces marneffei (TM), nontuberculous mycobacteria (NTM), mycobacterium tuberculosis (TB), or other pathogens, accompanied with CNS infections. In addition, we conducted a thorough literature review of AIGAs-positive patients with CNS infections. We report three HIV-negative cases of recurrent disseminated infections including CNS, and AIGAs were measured. All patients had no history of underlying diseases or immunosuppression and presented with fever, cough, and headache. They were negative for HIV antibodies but positive for AIGAs. The patients were diagnosed with CNS infections based on cerebrospinal fluid (CSF) examination and next-generation sequencing (NGS). All patients received anti-infective treatment according to different pathogens, and their condition remained stable without recurrence. In adults with severe and recurrent infections of multiple organs without known immunodeficiency, adult-onset immunodeficiency (AOID) associated with AIGAs should be considered. In AIGAs-positive patients, the blood–brain barrier (BBB) may be disrupted, leading to susceptibility to CNS infections.

The typical clinical characteristic of patients with anti-IFN-γ autoantibodies (AIGAs) is primarily associated with infection caused by intracellular pathogens. With continued research, additional clinical characteristics have been gradually uncovered. Here, we present a case of multiple pathogen infections accompanied by ocular pathologies in a patient with high titers of AIGAs. The patient, a 53-year-old female patient, was admitted to our hospital after finding a mass in the right supraclavicular fossa. She was successively diagnosed with Talaromyces marneffei, Aspergillus flavus and Nontuberculous mycobacteria (NTM) infections. Then, she received a complete course of antifungal agents for nearly 3.5 years and anti-NTM treatment for nearly 3 years, with discontinuation upon symptom improvement. However, there was a rapid recurrence of the infection upon cessation of the drug despite improvement in the patient's symptoms. Moreover, when the recurrent infection stabilized, the patient exhibited immune conjunctivitis and dry eye, which was successfully treated by tacrolimus eye drops and lubricant. Patients with high-titer AIGAs are more prone to experiencing recurrence and/or persistent infection, as well as immune disorders.

Background Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus–negative patient. Case presentation A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. Conclusions High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.