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IgA vasculitis or Henoch-Schönlein purpura: genetics and beyond

Koskela et al. published a genome-wide association study (GWAS) in children with IgA vasculitis (IgAV), also known as Henoch-Schonlein purpura (Pediatr Nephrol 2021 ; 36:2311–8), and confirmed the significance of exclusively HLA class II genes with IgAV susceptibility. This encouraged us to comment on the strengths and limitations of this research and to reflect on existing knowledge about genetics in IgAV. Since etiopathogenesis of IgAV is complex and may involve numerous interactions between various environmental and genetic factors, genomics alone cannot explain the entirety of the risk of IgAV. In addition to the role of the HLA class II genes, some studies have pointed to the importance of non-HLA genes, and modern geostatistical research has also indicated a geospatial risk distribution, which, according to similar research in IgA nephropathy, may suggest the strong influence of different environmental factors, such as climate, pathogen load, and dietary factors. There is increasing evidence that an integrative approach should be included in understanding of IgAV, in terms of the integration of genomics, proteomics, transcriptomics and epigenetics. This approach could result in the discovery of new pathways important for finding biomarkers that could stratify patients according to the risk of complications, and ultimately allow the development of new therapeutic approaches, especially important in the treatment of nephritis, as the most important chronic complication of the disease, for which there is still no standardized treatment.

IgA vasculitis ; Henoch-Schönlein purpura ; genetics ; genomics ; proteomics ; epigenetics

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