Distinct Lymphocyte Immunophenotyping and Quantitative Anti-Interferon Gamma Autoantibodies in Taiwanese HIV-Negative Patients with Non-Tuberculous Mycobacterial Infections

• Published in: Journal of clinical immunology 2023-05, Vol.43 (4), p.717-727
• Main Authors: Lee, Wen-I., Fang, Yao-Fan, Huang, Jing-Long, You, Huey-Ling, Hsieh, Meng-Ying, Huang, Wan-Ting, Liang, Chi-Jou, Kang, Chen-Chen, Wu, Ting-Shu
• Format: Article
• Language: English
• Subjects: Autoantibodies; Biomedical and Life Sciences; Biomedicine; CCR6 protein; CCR7 protein; CD19 antigen; CD20 antigen; CD38 antigen; CD4 antigen; CD57 antigen; CD8 antigen; CXCR3 protein; CXCR5 protein; Helper cells; Herpes zoster; HIV Infections; Humans; Immune system; Immunodeficiency; Immunoglobulin M; Immunologic Deficiency Syndromes - diagnosis; Immunology; Immunophenotyping; Infections; Infectious Diseases; Interferon-gamma; Interleukin 12; Internal Medicine; Lymphadenitis; Lymphocytes B; Lymphocytes T; Medical Microbiology; Memory cells; Middle Aged; Mycobacterium Infections, Nontuberculous - diagnosis; Nontuberculous Mycobacteria; Original Article; Osteomyelitis; Reactive oxygen species; Receptors, CCR7; Tuberculosis; γ-Interferon
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-022-01423-1

Purpose The presence of anti-interferon-γ autoantibodies (AutoAbs-IFN-γ) is not rare in patients suffering from persistent non-tuberculous mycobacterial (NTM) infections that are characteristic of adult-onset immunodeficiency syndrome. The immune disturbances in this distinct disorder remain to be elucidated. Methods Patients with NTM infections but without effective response over 3 months’ treatment were referred to our institute to quantify their level of AutoAbs-IFN-γ after excluding defective IL12/23-IFN-γ circuit and reactive oxygen species production. The AutoAbs-IFN-γ and percentage of lymphocyte subpopulations most relevant to T and B cell pools were assessed and compared with age-matched healthy controls. Results A total of 31 patients were enrolled during the 15-year study period (2008–2022), 20 patients with > 50% suppression of IFN-γ detection at 1:100 serum dilution were classified into the Auto-NTM group. The remaining 11 with negligible suppression were assigned to the No Auto-NTM group. Mycobacterium chimaera-intracellulare group (MAC), M. kansasii , and M. abscessus were the most common pathogens. Pneumonia (19 vs 7), lymphadenitis (11 vs 5), Salmonella  sepsis (6 vs 2), osteomyelitis (5 vs 1), and cutaneous herpes zoster (4 vs 4) were the main manifestations in both the Auto-NTM and No Auto-NTM groups who had similar onset-age (55.3 vs 53.6 years; p  = 0.73) and follow-up duration (71.9 vs 54.6 months;  p  = 0.45). The Auto-NTM group had significantly higher transitional (IgM +  + CD38 + +), CD19 + CD21-low, and plasmablast (IgM-CD38 + +) in the B cell pool, with higher effector memory (CD4 + /CD8 + CD45RO + CCR7 −), senescent CD8 + CD57 + , and Th17 cells, but lower naïve (CD4 + /CD8 + CD45RO − CCR7 +) and Treg cells in the T cell pool when compared to the No Auto-NTM and healthy groups. NTM patients with/without AutoAbs-IFN-γ had lower Th1-like Tfh (CD4 + CXCR5 + CXCR3 + CCR6 −) cells. All Auto-NTM patients still had non-remitted mycobacterial infections and higher AutoAbs-IFN-γ despite anti-CD20 therapy in 3 patients. Conclusion In patients with suspected adult-onset immunodeficiency syndrome, two thirds (20/31) were recognized as having significantly inhibitory AutoAbs-IFN-γ with higher antibody-enhancing transitional, CD19 + CD21-low and plasmablast B cells; as well as higher effector memory, senescent CD8 + CD57 + and Th17 cells, but lower naïve T and Treg cells in contrast to those with negligible AutoAbs-IFN-γ. Such immunophenotyp