{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:50:29Z","timestamp":1790704229816,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Isotype class\u2010switch recombination (CSR), somatic hypermutation (SHM), B cell signalling and DNA repair mechanisms defects are responsible for high IgM. The hyperimmunoglobulin M (HIGM) phenotype and CSR\u2010related defects are now classified under primary antibody defects, combined immunodeficiencies or syndromic immunodeficiencies groups. The aim of the study is to evaluate the diverse phenotypic\/genotypic\/laboratory characteristics and outcome of patients with CSR defects and HIGM\u2010related defects. We enrolled 50 patients. The most common gene defect was Activation\u2010induced cytidine deaminase (AID) deficiency (n\u00a0=\u00a018), followed by CD40 Ligand (CD40L) (n\u00a0=\u00a014) and CD40 (n\u00a0=\u00a03) deficiency. Median ages at first symptom and diagnosis were significantly lower in CD40L deficiency (8.5 and 30\u2009months, respectively) than AID deficiency (30 and 114\u2009months, respectively) (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.001 and <jats:italic>p<\/jats:italic>\u00a0=\u00a0.008, respectively). Frequent clinical symptoms were recurrent (66%) and severe (14.9%) infections, and\/or autoimmune\/non\u2010infectious inflammatory features (48.4%). Eosinophilia and neutropenia were at a higher rate in CD40L deficiency patients (77.8%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.002 and 77.8%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.002, respectively) when compared to AID deficiency. Median serum IgM level was low in 28.6% of CD40L deficiency patients. It was significantly lower when compared to AID deficiency (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Six patients (CD40L deficiency n\u00a0=\u00a04, CD40 deficiency n\u00a0=\u00a02) underwent hematopoietic stem cell transplantation. Five were alive at the last visit. Four patients two patients with CD40L deficiency, one with CD40 deficiency and one with AID deficiency had novel mutations. In conclusion; patients with CSR defects and HIGM phenotype may present with a wide range of clinical manifestations and laboratory findings. Low IgM, neutropenia and eosinophilia were prominent in patients with CD40L deficiency. Characterization of genetic defect\u2010specific clinical and laboratory features may ease the diagnosis, prevent the underdiagnoses of patients and ameliorate the outcome.<\/jats:p>","DOI":"10.1111\/sji.13213","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T08:12:38Z","timestamp":1660810358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A single\u2010center study points to diverse features and outcome in patients with Hyperimmunoglobulin M Syndrome and Class\u2010 Switch Recombination defects"],"prefix":"10.1111","volume":"96","author":[{"given":"Ay\u015feg\u00fcl","family":"Akarsu","sequence":"first","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevil","family":"Hala\u00e7l\u0131","sequence":"additional","affiliation":[{"name":"Hacettepe University, Health Science Institute, Institute of Child Health Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7a\u011fman","family":"Tan","sequence":"additional","affiliation":[{"name":"Hacettepe University, Health Science Institute, Institute of Child Health Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bar\u0131\u015f","family":"Ku\u015fkonmaz","sequence":"additional","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Hematology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alphan","family":"K\u00fcpesiz","sequence":"additional","affiliation":[{"name":"Akdeniz University Faculty of Medicine Department of Pediatric Hematology  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"\u00c7etinkaya","sequence":"additional","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Hematology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zden","family":"Sanal","sequence":"additional","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lhan","family":"Tezcan","sequence":"additional","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-4627","authenticated-orcid":false,"given":"Deniz","family":"\u00c7a\u011fda\u015f","sequence":"additional","affiliation":[{"name":"Hacettepe University Faculty of Medicine Department of Pediatric Immunology  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00758-x"},{"key":"e_1_2_8_3_1","unstructured":"Primary Immuno deficiency disease ISBN 978\u20103\u2010540\u201078537\u20108 pDSsIDI.368 line 7."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.09.013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18161"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-013-8378-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70123-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221456898"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2003.41"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00079-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2003.10.007"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni974"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00222.x"},{"key":"e_1_2_8_14_1","first-page":"101","article-title":"Immunodeficiency with hyper\u2010IgM (HIM)","volume":"3","author":"Notarangelo LD","year":"1992","journal-title":"Immunodefic Rev"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3904"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2012.750299"},{"key":"e_1_2_8_17_1","unstructured":"Diagnostic criteria for HIGMX:https:\/\/esid.org\/Working\u2010Parties\/Clinical\u2010Working\u2010Party\/Resources\/Diagnostic\u2010criteria\u2010for\u2010PID2#Q16. 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