{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:32:35Z","timestamp":1790652755336,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"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. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The pathogenesis of common variable immunodeficiency disorder (CVID) is complex, especially when combined with autoimmunity. Genetic factors may be potential explanations for this complex situation, and whole genome sequencing (WGS) provide the basis for this potential.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Genetic information of patients with CVID with autoimmunity, together with their first-degree relatives, was collected through WGS. The association between genetic factors and clinical phenotypes was studied using genetic analysis strategies such as sporadic and pedigree.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We collected 42 blood samples for WGS (16 CVID patients and 26 first-degree relatives of healthy controls). Through pedigree, sporadic screening strategies and low-frequency deleterious screening of rare diseases, we obtained 9,148 mutation sites, including 8,171 single-nucleotide variants (SNVs) and 977 Insertion-deletions (InDels). Finally, we obtained a total of 28 candidate genes (32 loci), of which the most common mutant was <jats:italic>LRBA.<\/jats:italic> The most common autoimmunity in the 16 patients was systematic lupus erythematosis. Through KEGG pathway enrichment, we identified the top ten signaling pathways, including \u201cprimary immunodeficiency\u201d, \u201cJAK-STAT signaling pathway\u201d, and \u201cT-cell receptor signaling pathway\u201d. We used PyMOL to predict and analyse the three-dimensional protein structures of the <jats:italic>NFKB1, RAG1, TIRAP, NCF2<\/jats:italic>, and <jats:italic>MYB<\/jats:italic> genes. In addition, we constructed a PPI network by combining candidate mutants with genes associated with CVID in the OMIM database via the STRING database.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The genetic background of CVID includes not only monogenic origins but also oligogenic effects. Our study showed that immunodeficiency and autoimmunity may overlap in genetic backgrounds.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration:<\/jats:bold> identifier ChiCTR2100044035<\/jats:p>","DOI":"10.3389\/fgene.2023.1209988","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T03:11:06Z","timestamp":1699931466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic characteristics of common variable immunodeficiency patients with autoimmunity"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhihui","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingying","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiye","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haopeng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/cei.12178","article-title":"New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin","volume":"174","author":"Ameratunga","year":"2013","journal-title":"Clin. 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