Background: Anti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data.Methods: This systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity.Results: We included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%).Conclusions: Intracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei, and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases.

Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. Methods: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. Results: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8⁺ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

Background: Little study has investigated the differences between Talatomyces marneffei (T. marneffei) respiratory infection and tuberculosis and the prognostic factors of such infection. This study investigated the characteristics and prognostic factors of T. marneffei infections with respiratory lesions and the causes of misdiagnosis. Methods: Clinical characteristics and prognoses of patients with T. marneffei infections with respiratory system lesion were investigated. T. marneffei diagnosis followed isolation from clinical specimens using standard culture, cytology, and histopathology. Survival curves were estimated by using Kaplan-Meier analysis, with log-rank test to compare differences in survival rates between groups. Univariate and multivariate Cox regression analyses were also performed to assess significant differences in clinical characteristics of overall survival. Results: Of 126 patients diagnosed with T. marneffei infections, 63 (50.0%) had T. marneffei respiratory system infections; 38.1% (24/63) were misdiagnosed as having tuberculosis. Human immunodeficiency virus (HIV) infection, CD4/CD8 < 0.5, percentage of CD4⁺ T cells 105 days were potential risk factors for poor prognoses. Length of time from onset to confirmation of diagnosis persisted as an independent predictor of all-cause mortality in multivariate analysis (odds ratio: 0.083, 95.0% confidence interval: 0.021–0.326, P < 0.001). However, the size of the lung lesions, dyspnea, thoracalgia, mediastinal lymphadenopathy, and pleural effusion did not significantly predict overall survival. There was no significant difference in prognosis according to the type of treatment. Conclusions: T. marneffei infections involving the respiratory system are common. The critical determinants of prognosis are HIV infection, CD4/CD8, percentage of CD4⁺ T cells, type of treatment, and the time range from onset to confirmation of diagnosis. Rapid and accurate diagnosis is crucial for improving prognosis.

BACKGROUND:Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The relationships of alcohol dehydrogenase (ADH) enzymes, encoded by the genes ADH1 (1A), ADH1B (ADH2), ADH1C (ADH3), ADH4, ADH5, ADH6, and ADH7, with...

Background: Few reports of Talaromyces marneffei (TM) or cryptococcosis infections among HIV-negative patients with high-titeranti–IFN-γautoantibodies (nAIGAs) have been published. We investigated the clinical manifestations of patients with nAIGAs and TM infections.Methods: HIV-negative adults (≥18 years) were enrolled if they haddisseminated TM infection (group 1; further divided into nAIGAs positive [group 1P] and negative [group 1N]); cryptococcosis(pulmonary cryptococcosis and/or cryptococcosis of the brain)(group 2); pulmonary tuberculosis (group 3); and healthy controls (group 4) with nAIGAs detected. Complete histories, physical examinations, and routine clinical laboratory tests were obtained at baseline.Results: Overall, 88 participants were in the four groups (20,13,23, and 32 in groups 1 to 4, respectively). Significant differences occurred between groups with higher nAIGAs titers (P < 0.001), and higher total white-cell and absolute neutrophil counts (P < 0.001) in group1. Lungs (90.0%), lymph nodes (60.0%), skin (55.0%), and bones (50.0%) were most common sites of involvement. Significant differences in total white-cell and absolute neutrophil counts occurred between groups IP and 1N.Patients with recurrent TM infections, particularly group 1P, had higher initial nAIGA titer.Conclusions: Patients with persistent infection who died tended to have positive initial nAIGA titer. It suggests that nAIGAs may play a critical role in the pathogenesis of TM infections, and may be associated with more severe, refractory infection.