The phenotypic difference of IgA nephropathy and its race/gender-dependent molecular mechanisms

Abstract

IgA nephropathy (IgAN), defined by the predominant deposition of IgA in the glomerular mesangium, is the most common form of glomerulonephritis throughout the world. However, its incidence, gender distribution, clinical presentation and progression and pathogenic initiating factors are largely variable on such simple definition. To assess the heterogeneity of this disease, we recently conducted clinical survey regarding presentation and clinical management of IgAN patients in Europe and Japan. This clinical survey highlights similarities and differences in patients from different continents. The survey revealed obvious differences between nations in the frequency of gastrointestinal complications including inflammatory bowel diseases (IBD) and celiac disease more frequent in European patients. Such findings are compatible with susceptibility loci related to intestinal immunity and IBD in recent genome wide association studies (GWAS) on IgAN. However, most of the molecules in these mucosal related loci fulfil the immunological function not only of gut-associated lymphoid tissue (GALT), but also nasopharyngeal/bronchial-associated lymphoid tissues (NALT/BALT). Indeed, similar frequency of macrohematuria coinciding with upper respiratory infection, known as hallmark manifestation of this disease, was found in the survey, emphasizing pathogenic roles of these molecules in NALT/BALT of IgAN patients. Recent experimental and clinical studies including GWAS on multiple common infections and IBD indicate immune cross talks between GALT and NALT/BALT and some related mediators such as TNF superfamily ligands (APRIL/BAFF). This review explains epidemiological heterogeneity of this disease with the clinical survey and discusses race and gender-dependent molecular mechanisms.