IgA vasculitis update: Epidemiology, pathogenesis, and biomarkers

Abstract

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children, characterized by diverse clinical manifestations with a wide spectrum ranging from isolated cutaneous vasculitis to systemic involvement. The incidence of IgAV is geographically and ethnically variable, with a prevalence in autumn and winter, suggesting a driving role that genetic and environmental factors play in the disease. Although IgAV has a certain degree of natural remission, it varies widely among individuals. Some patients can suffer from severe renal involvement and even progress to end-stage renal disease. Its pathogenesis is complex and has not been fully elucidated. The formation of galactose-deficient IgA1 (Gd-IgA1) and related immune complexes plays a vital role in promoting the occurrence and development of IgAV nephritis. In addition, neutrophil activation is stimulated through the binding of IgA to the Fc alpha receptor I expressed on its surface, resulting in systemic vascular inflammation and tissue damage. Starting from the epidemiological characteristics, this article will review the role of immunological factors such as Gd-IgA1, autoantibodies, circulating immune complexes, complement system, cellular immunization, and the contributions of environmental and genetic factors in the pathogenesis of IgAV, and conclude with the major biomarkers for IgAV.

Pathophysiology and clinical manifestations of immune complex vasculitides

“…This binding is catalyzed by several transferases such as polypeptide N-acetylgalactosaminyl transferase 2 or core-1 β1,3-galactosyltransferase (which catalyzed the binding of Gal to GalNAc) and acetylgalactosamine-specific α-2,6 sialic acid transferase, respectively. Altered expression and activities of galactosyltransferase would result in altered exposure of terminal GalNac residues or more Gd-IgA [for review, refer to Heineke et al (6), Barratt et al (12), and Xu et al (16)].…”

“…In addition, immortalized B cells from patients with IgAV and IgAV nephritis both produced similarly high amounts of GdIgA1, while cell lines from patients with IgAV without nephritis produced mostly normally galactosidated IgA (17). Formation of Gd-IgA1 at least in IgAN is additionally enhanced by interleukin-6 (IL-6), interleukin-4 (IL-4), and even by some miRNA (miR-148b); their respective actions result in reduced activity of transferases or other reactions in glycosylation [for review, refer to Xu et al (16)].…”

“…In IgAV, levels of circulating IgA immune complexes were significantly correlated with the detection of IgA in kidneys (29) and with the presence of signs of clinical and histological activity. These signs were the magnitude of microscopic hematuria, a past history of macroscopic hematuria, and the percentage of glomeruli with florid epithelial crescents [(30), for further literature, refer to (16)].…”

COVID-19 Vaccination as a Trigger of IgA Vasculitis: Truth or Illusion?

“…2 The temporal pattern of IgAV attacks provides clues to trace the association between infection and the pathogenesis of IgAV. 5 In this study, 1 is the prevalence of IgAV the same across seasons? Is the incidence of IgAV reduced by including more patients with onset in summer?…”

Immunoglobulin a vasculitis with testicular/epididymal involvement in children: A retrospective study of a ten-year period

“…Pathologically, IgAV is characterized by leukocytoclastic vasculitis involving small vessels, predominately due to IgA immune complex deposition (3). IgAV is mostly self-limiting, and most patients have a good prognosis, although severe renal, gastrointestinal, and other organ damage may occur (3)(4)(5).…”