IgA Nephropathy: Pleiotropic impact of Epstein-Barr virus infection on immunopathogenesis and racial incidence of the disease

Frontiers in Immunology

Immunology

Milan Raska¹  Bruce A. Julian²  Jiri Mestecky³ 

[1] Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States;Department of Immunology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czechia;Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States;Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States;Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States;Laboratory of Cellular and Molecular Immunology Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia;Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States;

关键词: IgA nephropathy;    Epstein-Barr virus;    galactose-deficient IgA1;    IgA system maturation;    age of infection;    virus spread;   

DOI  :  10.3389/fimmu.2023.1085922

 received in 2022-10-31, accepted in 2023-01-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

IgA nephropathy (IgAN) is an autoimmune disease in which poorly galactosylated IgA1 is the antigen recognized by naturally occurring anti-glycan antibodies, leading to formation of nephritogenic circulating immune complexes. Incidence of IgAN displays geographical and racial disparity: common in Europe, North America, Australia, and east Asia, uncommon in African Americans, many Asian and South American countries, Australian Aborigines, and rare in central Africa. In analyses of sera and cells from White IgAN patients, healthy controls, and African Americans, IgAN patients exhibited substantial enrichment for IgA-expressing B cells infected with Epstein-Barr virus (EBV), leading to enhanced production of poorly galactosylated IgA1. Disparities in incidence of IgAN may reflect a previously disregarded difference in the maturation of the IgA system as related to the timing of EBV infection. Compared with populations with higher incidences of IgAN, African Americans, African Blacks, and Australian Aborigines are more frequently infected with EBV during the first 1-2 years of life at the time of naturally occurring IgA deficiency when IgA cells are less numerous than in late childhood or adolescence. Therefore, in very young children EBV enters “non-IgA” cells. Ensuing immune responses prevent infection of IgA B cells during later exposure to EBV at older ages. Our data implicate EBV-infected cells as the source of poorly galactosylated IgA1 in circulating immune complexes and glomerular deposits in patients with IgAN. Thus, temporal differences in EBV primo-infection as related to naturally delayed maturation of the IgA system may contribute to geographic and racial variations in incidence of IgAN.

【 授权许可】

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Copyright © 2023 Mestecky, Julian and Raska