{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:42:36Z","timestamp":1763534556768,"version":"3.45.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005322","name":"Recep Tayyip Erdogan \u00dcniversitesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in\n                      <jats:italic>ALOX12B<\/jats:italic>\n                      , a crucial enzyme involved in epidermal lipid processing, are among the most common causes of autosomal recessive congenital ichthyosis (ARCI). Although traditionally considered a cutaneous disorder, the systemic immunological implications of ALOX12B deficiency remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to broaden the dermatologic and immunologic spectrum of ALOX12B-associated ARCI by characterizing the clinical, immunologic, and genetic features of six patients from three consanguineous families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective study included six patients with ALOX12B-associated ARCI identified through whole-exome sequencing. Detailed dermatological evaluations, infection histories, immunoglobulin profiles, lymphocyte subset analyses, and vaccine response assessments were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients exhibited early-onset generalized ichthyosis, ranging from delayed-onset lamellar ichthyosis to collodion membrane presentations accompanied by nonbullous erythroderma. Two distinct biallelic\n                      <jats:italic>ALOX12B<\/jats:italic>\n                      variants were identified: a novel p.Thr383Lys and the known p.Cys544Arg. Several patients demonstrated recurrent bacterial or fungal infections (n = 5), markedly elevated serum IgE levels (n = 4), and isolated abnormalities in vaccine responsiveness (n = 2). Lymphocyte counts and other immunoglobulin classes were generally preserved; however, decreased IgG levels were observed in one patient (P3.1). Intravenous immunoglobulin replacement therapy reduced the frequency of infections in patients (P1.1 and P1.2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that ALOX12B-related ARCI may involve secondary immune dysregulation, driven by chronic compromise of the epidermal barrier. An immunologic evaluation is warranted in selected cases, particularly those with a history of susceptibility to infections. Multidisciplinary care, encompassing dermatology, immunology, and genetics, is crucial for achieving optimal outcomes in ARCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1662858","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:38:14Z","timestamp":1763534294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the skin: immunological profiles and infectious complications in ALOX12B-associated autosomal recessive congenital ichthyosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Asena Pinar","family":"Sefer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet 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