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Review
. 2021 Nov 9:12:771619.
doi: 10.3389/fimmu.2021.771619. eCollection 2021.

Pathogenesis of IgA Vasculitis: An Up-To-Date Review

Yan Song  1   2   3   4   5 , Xiaohan Huang  1   2   3   4   5 , Guizhen Yu  1   2   3   4   5 , Jianjun Qiao  6 , Jun Cheng  1   2   3   4   5 , Jianyong Wu  1   2   3   4   5 , Jianghua Chen  1   2   3   4   5
Affiliations
Review

Pathogenesis of IgA Vasculitis: An Up-To-Date Review

Yan Song et al. Front Immunol. .

Abstract

Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.

Keywords: IgA; IgA vasculitis; kidney; pathogenesis; skin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Model: pathogenesis of IgA vasculitis. The mucosal antigen can activate B-cells in MALT through T-cell-dependent or independent ways. The latter activates B-cells through TLR pathways. With genetic factors, the activated B-cells become plasma cells and produce Gd-IgA1. Gd-IgA1 and anti-Gd-IgA1 autoantibodies form circulating immune complexes together with other components (including sCD89 or complements). Then, the immunocomplex deposit at organs and activate inflammatory responses. In the kidney, the immunocomplex can activate mesangial cells through TfR, leading to the apoptosis of renal cells and recruitment of inflammatory cells. (ADCC, antibody-dependent cytotoxicity; CDC, complement-dependent cytotoxicity; Gd-IgA1, Galactose-deficient IgA1; MAC, membrane attack complex; MALT, Mucosa-associated lymphoid tissue; NET, neutrophil extracellular traps; TfR, transferrin receptor).
Figure 2
Figure 2
IgA1 Oglycans (A) Structure of human IgA1. The hinge region of IgA1 usually contains three to six O-linked glycan sites. (B) Variants of IgA1 O-glycan. (C) Synthesis of human IgA1 O-glycans. Upregulated α-N-acetylgalactosaminide α2,6-sialyltransferase 2 and down regulated core 1 β1,3-galactosyltransferase (and Cosmc) can lead to the increase of galactose-deficient IgA1.
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