{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:40:54Z","timestamp":1777887654696,"version":"3.51.4"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency belonging to the spectrum of common variable immunodeficiency disorders, frequently associated with immune dysregulation, autoimmunity, and lymphoproliferation. Its clinical presentation is highly heterogeneous, ranging from isolated autoimmune cytopenias to severe multisystem involvement. Here, we report five cases of LRBA deficiency from five Moroccan families, highlighting the broad clinical variability of this condition. The first patient presented with chronic immune thrombocytopenic purpura (ITP) as the initial and predominant manifestation, associated with hypogammaglobulinemia. The second patient developed ITP complicated by a hemorrhagic syndrome and significant lymphoproliferation, including splenomegaly and hepatomegaly. The third patient initially presented with autoimmune hemolytic anemia (AIHA), followed by splenomegaly. The fourth patient exhibited a complex clinical course, beginning with bicytopenia and progressing to enteropathy, arthritis, pneumopathy, and type 1 diabetes mellitus, associated with splenomegaly, hepatomegaly, and lymphadenopathy. Finally, the fifth patient initially presented with ITP and subsequently developed bilateral panuveitis, arthritis, and recurrent respiratory infections. Targeted next-generation sequencing identified homozygous pathogenic variants in the\n                    <jats:italic>LRBA<\/jats:italic>\n                    gene in all five patients, consistent with a loss-of-function mechanism. These included the nonsense variants c.3811C&amp;gt;T (p.Arg1271*) and c.5692G&amp;gt;T (p.Glu1898*), a large deletion encompassing exons 30 to 34, the frameshift variant c.5060_5067delACATACCA (p.Asn1687Serfs*21), and an extended deletion involving part of exon 4 (c.476_549\u00a0+\u00a0580del). All patients required immunosuppressive therapy and\/or immunoglobulin replacement. LRBA deficiency should be considered in children presenting with autoimmune cytopenias, lymphoproliferation, and multisystem autoimmunity. The marked heterogeneity of clinical manifestations underscores the importance of early molecular diagnosis to guide therapeutic decision-making. In our experience, prompt recognition and the initiation of targeted therapies, such as abatacept or early hematopoietic stem cell transplantation, may improve patient outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1807421","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:19:59Z","timestamp":1777609199000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Different faces of LRBA deficiency in five Moroccan families"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohamed","family":"Hbibi","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology-Oncology, SHOP, CHU Hassan II","place":["Fez, Morocco"]},{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahamada","family":"Elamine","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibtihal","family":"Benhsaien","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]},{"name":"Department of Pediatric Infectious Diseases and Clinical Immunology, Mother-Child Hospital Abderrahim El Harouchi, Ibn Rochd University Hospital Center.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mounia Lakhdar","family":"Idrissi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHU Hassan II","place":["Fez, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Tizki","sequence":"additional","affiliation":[{"name":"Pediatrics department, Faculty of Medicine and Pharmacy. University Hospital Center Mohammed VI, Ibn ZOHR University","place":["Agadir, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jalila El","family":"Bakkouri","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moustapha","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CHU Hassan II","place":["Fez, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Ailal","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]},{"name":"Department of Pediatric Infectious Diseases and Clinical Immunology, Mother-Child Hospital Abderrahim El Harouchi, Ibn Rochd University Hospital Center.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Aziz","family":"Bousfiha","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA). Faculty of Medicine and Pharmacy. Hassan II University.","place":["Casablanca, Morocco"]},{"name":"Department of Pediatric Infectious Diseases and Clinical Immunology, Mother-Child Hospital Abderrahim El Harouchi, Ibn Rochd University Hospital Center.","place":["Casablanca, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1016\/j.jaip.2019.04.011","article-title":"Clinical, immunologic, and molecular spectrum of patients with LPS-responsive beige-like anchor protein deficiency: a systematic review","volume":"7","author":"Habibi","year":"2019","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2017.50","article-title":"Murine LRBA deficiency causes CTLA-4 deficiency in Tregs without progression to immune dysregulation","volume":"95","author":"Burnett","year":"2017","journal-title":"Immunol Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00799-2","article-title":"Clinical phenotypes and immunological characteristics of 18 Egyptian LRBA deficiency patients","volume":"40","author":"Meshaal","year":"2020","journal-title":"J ClinImmunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.jaci.2014.10.019","article-title":"Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked\u2013like disorder caused by loss-of-function mutations in LRBA","volume":"135","author":"Charbonnier","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.ajhg.2012.04.015","article-title":"Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity","volume":"90","author":"Lopez-Herrera","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.70962\/jhi.20250002","article-title":"The 2024 update of IUIS phenotypic classification of human inborn errors of immunity","volume":"1","author":"Bousfiha","year":"2025","journal-title":"J Hum Immun"},{"key":"B8","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.jaci.2012.05.043","article-title":"LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency","volume":"130","author":"Alangari","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1016\/j.jaip.2019.06.011","article-title":"Abatacept as a long-term targeted therapy for LRBA deficiency","volume":"7","author":"Kiykim","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B10","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":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.025","article-title":"The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency","volume":"137","author":"G\u00e1mez-D\u00edaz","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1351076","article-title":"Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - 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