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Immunol."],"abstract":"<jats:p>Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac\/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac\/celiac-like disease, as treatment implications are significant.<\/jats:p>","DOI":"10.3389\/fimmu.2022.894648","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T05:04:25Z","timestamp":1658466265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report"],"prefix":"10.3389","volume":"13","author":[{"given":"Lauren V.","family":"Collen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Andres","family":"Salgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dascha","family":"Weir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Leichtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Sabery Khavari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Gernez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Snapper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3108","article-title":"The Emerging Role of CTLA4 as a Cell-Extrinsic Regulator of T Cell Responses","volume":"11","author":"Walker","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3746","article-title":"Autosomal Dominant Immune Dysregulation Syndrome in Humans With CTLA4 Mutations","volume":"20","author":"Schubert","year":"2014","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/imr.12721","article-title":"What did We Learn From CTLA-4 Insufficiency on the Human Immune System","volume":"287","author":"Mitsuiki","year":"2019","journal-title":"Immunol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02012","article-title":"Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers","volume":"9","author":"Egg","year":"2018","journal-title":"Front Immunol"},{"key":"B5","volume-title":"Roitt's Essential Immunology","author":"Delves","year":"2018"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.055","article-title":"Phenotype, Penetrance, and Treatment of 133 Cytotoxic T-Lymphocyte Antigen 4-Insufficient Subjects","volume":"142","author":"Schwab","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","article-title":"International Consensus Document (ICON): Common Variable Immunodeficiency Disorders","volume":"4","author":"Bonilla","year":"2016","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-745174","article-title":"Identifying Functional Defects in Patients With Immune Dysregulation Due to LRBA and CTLA-4 Mutations","volume":"129","author":"Hou","year":"2017","journal-title":"Blood."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.jaci.2017.05.022","article-title":"Exaggerated Follicular Helper T-Cell Responses in Patients With LRBA Deficiency Caused by Failure of CTLA4-Mediated Regulation","volume":"141","author":"Alroqi","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa417.041","article-title":"42. 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