Cheng Brooke, Bajwa Barinder, Choi Seungwon, Martin Hannah, Miao Tyson, Werry Denise, Perlman Michael, Mirzanejad Yazdan
Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada.
Faculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Trop Med Infect Dis. 2025 Jul 21;10(7):202. doi: 10.3390/tropicalmed10070202.
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.
抗细胞因子自身抗体（AAbs），尤其是抗干扰素-γ（抗IFN-γ）自身抗体，会破坏细胞因子功能，导致感染、自身免疫样疾病以及类似白细胞介素-12（IL-12）/IFN-γ通路缺陷的病症。基因检测的进展已经阐明了自身炎症性疾病、自身免疫性疾病和原发性免疫缺陷之间的重叠，但也揭示了复杂的表型和通路。虽然这些见解加深了我们对免疫机制的理解，但它们也使诊断和治疗变得复杂，对于由基因突变引起的IFN-γ缺乏症，治疗选择有限。成人期出现的由非结核分枝杆菌（NTM）和其他机会性感染引起的伴有播散性淋巴结炎的免疫缺陷与高水平的抗IFN-γ自身抗体有关。这种综合征最初在HIV阴性的亚洲患者中被发现，经常影响亚洲血统的个体，并且可能与特定的人类白细胞抗原（HLA）等位基因有关。中和性抗IFN-γ自身抗体的存在会损害IFN-γ依赖的免疫反应，可能导致NTM持续感染。这项研究强调了迟发性抗IFN-γ自身抗体综合征可能表现为播散性NTM（dNTM）感染的可能性，突出了及时诊断的重要性，并考虑将利妥昔单抗作为一种潜在的治疗选择。
