What is new in the pathogenesis and treatment of IgA glomerulonephritis

Table 1 The summary of the four hits involved in the pathogenesis of IgA nephritis

Hit	Pathogenetic process	Putative environmental factors involved	Putative genetic factors involved	Potential clinical biomarkers	Potential novel therapeutic approaches
1	Hereditary increase in circulating galactose-deficient IgA1	Potential role of mucosal exposure to infectious of dietary antigens	Strong evidence for high heritability of serum galactose-deficient IgA1 level. Potential role of chromosome 22q12.2	Serum galactose-deficient IgA1 level (HAA based ELISA)	Suppression of synthesis of galactose-deficient IgA1. Enzymatic boost of galactose transfer to IgA1 hinge region O-glycans
2	Circulating antibody directed against galactose-deficient IgA1	Potential role of mucosal exposure to infectious or dietary antigens	Potential role of three MHC-II loci in antigen presentation and humoral response to galactose-deficient IgA1 O-glycans	Serum anti-glycan antibodies (dot-blot assay)	Alteration of processing and presentation of galactose-deficient IgA1 O-glycopeptides. Specific B-cell depletion therapy
3	Formation of pathogenic IgA1-containing immune complexes	Unknown	Unknown	Circulating and/or urinary immune complexes	Competitive blockade of immune complex formation by non-cross-linking anti-glycan antibodies or specific glycopeptides
4	Mesangial deposition of IgA1-containing immune complexes, cell activation and initiation of glomerular injury	Unknown	Protective effect of common deletion in CFHR1 and CFHR3	Circulating and/or urinary complement degradation products, or novel markers of glomerular injury	Suppression of the alternative complement pathway. Targeted CFHR1/3 depletion. Blocking mesangial cell signaling induced by nephritogenic IgA1-containing immune complexes

HAA: Helix aspersa agglutinin; ELISA: Enzyme-linked immunosorbent assay; MHC-II: Major histocompatibility complex.