{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T15:40:26Z","timestamp":1742830826750,"version":"3.40.2"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Common variable immunodeficiency (CVID), the most frequent symptomatic primary immune deficiency in humans, is a heterogeneous group of immunologic disorders estimated to affect 1:10,000\u20131:50,000. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG Ab production in response to infection or vaccination. Patients often also exhibit autoimmune cytopenias with symptoms of abnormal T cell function, including reductions in naive T cells, which correlate with clinical severity. In this study, we discovered that targeted alterations in the glycome of the myeloid lineage lead to spontaneous immunodeficiency characteristic of both humoral and T cell dysfunction regularly found in human CVID. Mice carrying a myeloid-specific knockout of the Mgat2 gene encoding UDP-GlcNAc:\u03b1-6-d-mannoside \u03b2-1,2-N-acetylglucosaminyltransferase II enzyme exhibit deficiencies in IgG responses to both protein and polysaccharide conjugate vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity because of a persistent autoimmune-mediated depletion of naive T cells, which is induced by changes in erythrocyte surface glycosylation. The N-glycosylation dependent autoepitopes that emerge on erythrocytes lead to autoimmune hemolytic anemia, and the causative auto-IgM cross-reacts with naive T cells despite the lack of glycan change on T cells. These findings demonstrate that alterations in erythrocyte glycosylation trigger the development of autoantibodies directed at both erythrocytes and naive T cells, revealing a possible mechanistic link between the induction of autoimmune hemolytic anemia, the reduction in naive T cells, and poor Ab responses to vaccine in severe CVID patients.<\/jats:p>","DOI":"10.4049\/jimmunol.1400385","type":"journal-article","created":{"date-parts":[[2014,5,3]],"date-time":"2014-05-03T06:22:05Z","timestamp":1399098125000},"page":"5561-5570","source":"Crossref","is-referenced-by-count":3,"title":["Myeloid Glycosylation Defects Lead to a Spontaneous Common Variable Immunodeficiency-like Condition with Associated Hemolytic Anemia and Antilymphocyte Autoimmunity"],"prefix":"10.1093","volume":"192","author":[{"given":"Sean O","family":"Ryan","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek W","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian A","family":"Cobb","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,6,15]]},"reference":[{"key":"2025032404351369000_r1","first-page":"1","article-title":"Primary immunodeficiency diseases. 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