{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:36:17Z","timestamp":1793500577474,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Autoantibodies against interferon-\u03b3 (AIGA) impair the IFN-\u03b3\u2013interleukin 12 pathway. The disease is underrecognized, leading to profound diagnostic and therapeutic delays. Evidence on treatment strategies, particularly B-cell depletion, remains limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the utility of Stat1 phosphorylation (pStat1) neutralization assays to guide management of AIGA immunodeficiency.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This ambispective longitudinal cohort study of patients with confirmed AIGA immunodeficiency was performed at Queen Mary Hospital, as the only center performing AIGA testing under Hong Kong\u2019s unified public health care system. The AIGA Prospective Registry of Outcomes, Treatment and Evaluating Clinical Trajectories (PROTECT) reviews patients with AIGA immunodeficiency in Hong Kong, with a focus on rituximab response. Participants included patients with AIGA immunodeficiency demonstrated by positive enzyme-linked immunosorbent assay findings with pStat1 inhibition recruited into the AIGA-PROTECT registry. Demographic, clinical, and laboratory data were collected longitudinally from January 1, 2021, to November 30, 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n All patients diagnosed with AIGA immunodeficiency were evaluated for rituximab therapy by the attending immunologist on a case-by-case basis. Treatment decisions were guided by clinical severity, infection burden, and patient preference, following detailed counselling on potential benefits and risks.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Demographic characteristics, medical history (with detailed documentation of prior and incident hospitalizations), physical examination findings, laboratory investigations including serial pStat1 neutralizing assays, and longitudinal clinical progress were collected. For patients treated with rituximab, their laboratory and clinical parameters before and after treatment were compared.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 38 patients with AIGA immunodeficiency were recruited. Patients experienced disseminated infections from multiple pathogens. Twenty-one patients (55.3%) received rituximab, which was associated with reduced patient hospitalizations (odds ratio, 25.00 [95% CI, 1.48-422.26];\n P<\/jats:italic>\n \u2009&amp;lt; .001) and annual hospitalization rates (median difference, \u22123.0 [95% CI, \u22125.0 to \u22121.0];\n P<\/jats:italic>\n \u2009=\u2009.008). Serial monitoring of pStat1 neutralization aligned with clinical events.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study presents a detailed analysis of clinical features, course of disease, and outcomes of rituximab treatment in patients with AIGA immunodeficiency in a clinical setting. These findings suggest that serial monitoring via pStat1 assays is a valuable tool for monitoring treatment response and guiding clinical management.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.23220","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:00:30Z","timestamp":1784127630000},"page":"e2623220","source":"Crossref","is-referenced-by-count":1,"title":["Prospective Registry of Outcomes, Treatment, and Clinical Trajectories for Anti\u2013IFN-\u03b3 Immunodeficiency"],"prefix":"10.1001","volume":"9","author":[{"given":"Valerie","family":"Chiang","sequence":"first","affiliation":[{"name":"Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freya Kit Lam","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nga Yi","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Ki","family":"Ip","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon Kwok Ho","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Kwong Yew","family":"Hooi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Chi Yan","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Yuen Ling","family":"Au","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip Hei","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR. 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