{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:04:18Z","timestamp":1779782658607,"version":"3.53.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Suppressor of cytokine signaling 1 (SOCS1) haploinsufficiency is an inborn error of immunity with dysregulated Janus kinase (JAK)\u2013signal transducer and activator of transcription (STAT) signaling and heterogeneous autoimmune, infectious, and inflammatory phenotypes; its spectrum and management remain unclear. We report a 29-year-old woman with a novel heterozygous SOCS1 variant (c.494C&amp;gt;T; p.Pro165Arg) identified by whole-exome sequencing. Variant impact was assessed in silico (combined annotation dependent depletion, conservation mapping, AlphaFold3, and PremPS) and functionally by measuring total and phosphorylated STAT1 (p-STAT1) expression in patient vs control cells at baseline and after interferon-\u03b3 stimulation. We also reviewed data from 20 previously reported SOCS1-deficient patients. The patient had granulomatous lymphocytic interstitial lung disease (GLILD), rheumatoid arthritis, inflammatory bowel disease-like enteropathy, and hypogammaglobulinemia, initially diagnosed with common variable immune deficiency. GLILD responded to rituximab; sirolimus was ineffective for enteropathy. Segregation revealed an asymptomatic father carrying the same variant. The patient was found to have an additional heterozygous TACI gene variant. Poststimulation flow cytometry showed higher STAT1 [24.7 vs 5.8 median fluorescence intensity (MFI)] and p-STAT1 (43.4 vs 2.4 MFI) levels; however, these differences were not statistically significant (P &amp;gt; 0.05). Structural modeling predicted Src homology 2 domain destabilization (\u0394\u0394G + 1.16\u2005kcal\/mol). Literature synthesis for SOCS1 deficiency patients (n = 21) showed median symptom onset of 8 years (range 5 months to 44 years), autoimmune diseases (immune thrombocytopenia, psoriasis, etc.), and frequent immunophenotypic abnormalities: lymphopenia 4\/8 (50%); high IgE 5\/7 (71.4%); low CD3+ 11\/17 (64.7%); CD4+ 6\/19 (31.5%); CD8+ 5\/17 (29.4%); B cells 5\/17 (29.4%); and natural killer (NK) cells 4\/19 (21%). SOCS1 haploinsufficiency presents heterogeneous phenotypes with variable penetrance. Early genetic testing and targeted interventions, such as JAK inhibitors or cytokine-blocking biologics, may improve outcomes.<\/jats:p>","DOI":"10.1093\/cei\/uxag023","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:42:59Z","timestamp":1778154179000},"source":"Crossref","is-referenced-by-count":0,"title":["Suppressor of cytokine signaling 1 haploinsufficiency in a patient with granulomatous lymphocytic interstitial lung disease and inflammatory bowel disease\u2013like disease"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3488-0283","authenticated-orcid":false,"given":"Gamze","family":"Sonmez","sequence":"first","affiliation":[{"name":"Hacettepe University Faculty of Medicine , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Yaz","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pediatric Basic Sciences, Institute of Child Health, Hacettepe University , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8539-2793","authenticated-orcid":false,"given":"Ceren","family":"Ustun","sequence":"additional","affiliation":[{"name":"Division of Pediatric Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Sahin","sequence":"additional","affiliation":[{"name":"School of Medicine, Selcuk University , Konya ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnar","family":"Aliyeva","sequence":"additional","affiliation":[{"name":"Division of Pediatric Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Babaoglu","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Ankara Medicana International Hospital , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzin","family":"Ozden","sequence":"additional","affiliation":[{"name":"Department of Adult Allergy and Clinical Immunology, Adana City Training and Research Hospital , Adana ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevil Oskay","family":"Halacli","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pediatric Basic Sciences, Institute of Child Health, Hacettepe University , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Cagdas","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pediatric Basic Sciences, Institute of Child Health, Hacettepe University , Ankara ,","place":["Turkey"]},{"name":"Division of Pediatric Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine , Ankara ,","place":["Turkey"]},{"name":"Division of Pediatric Immunology, Ihsan Dogramaci Childrens Hospital, Hacettepe University Faculty of Medicine , Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"2026052603314441200_uxag023-B1","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1038\/s41467-020-18925-4","article-title":"Early-onset autoimmunity associated with SOCS1 haploinsufficiency","volume":"11","author":"Hadjadj","year":"2020","journal-title":"Nat Commun"},{"key":"2026052603314441200_uxag023-B2","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s10875-023-01495-7","article-title":"Insights into the expanding intestinal phenotypic spectrum 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