{"doi":"10.3389/fimmu.2020.00267","title":"Role of Epstein-Barr Virus in Pathogenesis and Racial Distribution of IgA Nephropathy","abstract":"IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circulating immune complexes with nephritogenic consequences. Because human B cells infected in vitro with Epstein-Barr virus (EBV) secrete galactose-deficient IgA1, we examined peripheral blood B cells from adult IgAN patients, and relevant controls, for the presence of EBV and their phenotypic markers. We found that IgAN patients had more lymphoblasts/plasmablasts that were surface-positive for IgA, infected with EBV, and displayed increased expression of homing receptors for targeting the upper respiratory tract. Upon polyclonal stimulation, these cells produced more galactose-deficient IgA1 than did cells from healthy controls. Unexpectedly, in healthy African Americans, EBV was detected preferentially in surface IgM- and IgD-positive cells. Importantly, most African Blacks and African Americans acquire EBV within 2 years of birth. At that time, the IgA system is naturally deficient, manifested as low serum IgA levels and few IgA-producing cells. Consequently, EBV infects cells secreting immunoglobulins other than IgA. Our novel data implicate Epstein-Barr virus infected IgA+ cells as the source of galactose-deficient IgA1 and basis for expression of relevant homing receptors. Moreover, the temporal sequence of racial-specific differences in Epstein-Barr virus infection as related to the naturally delayed maturation of the IgA system explains the racial disparity in the prevalence of IgAN.","journal":"Frontiers in Immunology","year":2020,"id":98996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":489301,"name":"Petr Kosztyu","orcid":null,"position":1,"is_corresponding":false},{"id":488002,"name":"Josef Zadražil","orcid":"0000-0001-8388-3133","position":2,"is_corresponding":false},{"id":489302,"name":"K Matoušovic","orcid":null,"position":3,"is_corresponding":false},{"id":488003,"name":"Karel Vondrák","orcid":"0000-0002-0378-8820","position":4,"is_corresponding":false},{"id":488004,"name":"Petr Hubáček","orcid":"0000-0002-6030-2604","position":5,"is_corresponding":false},{"id":71222,"name":"Bruce A. Julian","orcid":"0000-0001-5781-1021","position":6,"is_corresponding":false},{"id":430455,"name":"Zina Moldoveanu","orcid":"0000-0002-5372-5262","position":7,"is_corresponding":false},{"id":430160,"name":"Zdeněk Novák","orcid":"0000-0003-4714-7344","position":8,"is_corresponding":false},{"id":488005,"name":"Klara Kostovcikova","orcid":"0000-0003-1821-398X","position":9,"is_corresponding":false},{"id":424892,"name":"Milan Raška","orcid":"0000-0002-8572-7246","position":10,"is_corresponding":false},{"id":488006,"name":"Jiří Městecký","orcid":"0000-0001-8133-2119","position":11,"is_corresponding":false},{"id":489300,"name":"Kateřina Zachová","orcid":null,"position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32184780","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}