Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection.

Background: The clinical syndrome of disseminated nontuberculous mycobacterial (NTM) infection in patients who were previously healthy is now well recognized to be associated with an acquired autoantibody to Interferon gamma (Anti IFN- γ autoantibody). However, the risk factors of this syndrome remain unknown.

Method: We performed an unmatched case control study among patients with NTM diseases who were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method. Cases were patients with NTM diseases and detectable anti IFN- γ autoantibody. Controls were randomly selected from those with undetectable anti IFN- γ autoantibody. Data from both groups including demographic data, clinical presentation, laboratory results, other risk factors and HLA genotypes were collected. Univariate and multivariate analyses were performed to identify independent risk factors for this syndrome.

Results: 70 cases (mean age 50 ± 11 years) and 70 controls (mean age 58 ± 18 years) were enrolled into the study. Mycobacterial abscessus was the most common NTM pathogen found in both groups (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM disease was significantly more common in cases (92.9%) than in the controls (14.3%, p<0.001). Binary logistic regression analysis showed that previous OIs (adjusted OR14.87, 95% CI 2.36-93.86), birthplace outside Central region (adjusted OR 19.19, 95% CI 3.86-95.35), lack of comorbidities lead to immunosuppression, such as HIV infection or diabetes mellitus (adjusted OR 23.68, 95% CI 4.01-139.94), and presence of HLA DRB1*15/16 (adjusted OR 153.28, 95% CI 16.87-139.88) were independent factors associated with this syndrome.

Conclusion: Patients with NTM disease associated with anti IFN- γ autoantibody are almost always previously healthy and HIV negative. Most of these patients presented with disseminated NTM disease with generalized lymphadenitis and often with reactive skin lesions. Factors associated with detectable anti IFN- γ autoantibody are HLA-DRB1 and DQB1 alleles, and history of previous OIs in patients without comorbidity that leads to immunosuppression. Further studies are needed to better understand these associations and to improve the treatment outcome.