Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature
Anticytokine autoantibodies (AAbs), particularly anti-interferon-gamma (anti-IFN-γ) AAbs, disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling interleukin-12 (IL-12)/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between a...
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MDPI AG
2025-07-01
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| Series: | Tropical Medicine and Infectious Disease |
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| Online Access: | https://www.mdpi.com/2414-6366/10/7/202 |
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| author | Brooke Cheng Barinder Bajwa Seungwon Choi Hannah Martin Tyson Miao Denise Werry Michael Perlman Yazdan Mirzanejad |
| author_facet | Brooke Cheng Barinder Bajwa Seungwon Choi Hannah Martin Tyson Miao Denise Werry Michael Perlman Yazdan Mirzanejad |
| author_sort | Brooke Cheng |
| collection | DOAJ |
| description | Anticytokine autoantibodies (AAbs), particularly anti-interferon-gamma (anti-IFN-γ) AAbs, disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling interleukin-12 (IL-12)/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between autoinflammatory, autoimmune disorders, and primary immunodeficiencies but reveal complex phenotypes and pathways. While these insights deepen our understanding of immune mechanisms, they also complicate diagnosis and treatment, with limited options for IFN-γ deficiencies caused by genetic mutations. The adult-onset immunodeficiency with disseminated lymphadenitis due to nontuberculous mycobacteria (NTM) and other opportunistic infections has been linked to high levels of anti-IFN-γ AAbs. This syndrome, initially identified in HIV-negative Asian patients, frequently affects individuals of Asian descent and may be associated with specific human leukocyte antigen (HLA) alleles. The presence of neutralizing anti-IFN-γ AAbs impairs the IFN-γ-dependent immune response, likely contributing to the persistent NTM infection. This study underscores the potential for late-onset anti-IFN-γ AAb syndrome to manifest with disseminated NTM (dNTM) infections, highlights the importance of timely diagnosis and considers rituximab as a potential therapeutic option. |
| format | Article |
| id | doaj-art-75fd4a0bbe914abe8de9da75e11fdff1 |
| institution | Kabale University |
| issn | 2414-6366 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Tropical Medicine and Infectious Disease |
| spelling | doaj-art-75fd4a0bbe914abe8de9da75e11fdff12025-08-20T03:32:28ZengMDPI AGTropical Medicine and Infectious Disease2414-63662025-07-0110720210.3390/tropicalmed10070202Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of LiteratureBrooke Cheng0Barinder Bajwa1Seungwon Choi2Hannah Martin3Tyson Miao4Denise Werry5Michael Perlman6Yazdan Mirzanejad7Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, BC V5Z 1M9, CanadaFaculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaDepartment of Medicine, Queen’s University, 94 Stuart Street, Kingston, ON K7L 3N6, CanadaFaculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaDivision of Infectious Diseases, Surrey Memorial Hospital, 13750 96 Ave., Surrey, BC V3V 1Z2, CanadaDivision of Infectious Diseases, Surrey Memorial Hospital, 13750 96 Ave., Surrey, BC V3V 1Z2, CanadaDivision of General Internal Medicine, University of British Columbia, 5913-1081 Burrard Street, Vancouver, BC V6Z 1Y6, CanadaDivision of Infectious Diseases, Surrey Memorial Hospital, 13750 96 Ave., Surrey, BC V3V 1Z2, CanadaAnticytokine autoantibodies (AAbs), particularly anti-interferon-gamma (anti-IFN-γ) AAbs, disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling interleukin-12 (IL-12)/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between autoinflammatory, autoimmune disorders, and primary immunodeficiencies but reveal complex phenotypes and pathways. While these insights deepen our understanding of immune mechanisms, they also complicate diagnosis and treatment, with limited options for IFN-γ deficiencies caused by genetic mutations. The adult-onset immunodeficiency with disseminated lymphadenitis due to nontuberculous mycobacteria (NTM) and other opportunistic infections has been linked to high levels of anti-IFN-γ AAbs. This syndrome, initially identified in HIV-negative Asian patients, frequently affects individuals of Asian descent and may be associated with specific human leukocyte antigen (HLA) alleles. The presence of neutralizing anti-IFN-γ AAbs impairs the IFN-γ-dependent immune response, likely contributing to the persistent NTM infection. This study underscores the potential for late-onset anti-IFN-γ AAb syndrome to manifest with disseminated NTM (dNTM) infections, highlights the importance of timely diagnosis and considers rituximab as a potential therapeutic option.https://www.mdpi.com/2414-6366/10/7/202mycobacterium avium complexnontuberculous mycobacteriarituximabinterferon gammaimmune deficiencycase series |
| spellingShingle | Brooke Cheng Barinder Bajwa Seungwon Choi Hannah Martin Tyson Miao Denise Werry Michael Perlman Yazdan Mirzanejad Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature Tropical Medicine and Infectious Disease mycobacterium avium complex nontuberculous mycobacteria rituximab interferon gamma immune deficiency case series |
| title | Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature |
| title_full | Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature |
| title_fullStr | Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature |
| title_full_unstemmed | Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature |
| title_short | Anti-IFN-γ Autoantibody Syndrome Presenting with Disseminated Nontuberculous Mycobacteria Infections: A Case Series of Therapeutic Implications and Review of Literature |
| title_sort | anti ifn γ autoantibody syndrome presenting with disseminated nontuberculous mycobacteria infections a case series of therapeutic implications and review of literature |
| topic | mycobacterium avium complex nontuberculous mycobacteria rituximab interferon gamma immune deficiency case series |
| url | https://www.mdpi.com/2414-6366/10/7/202 |
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