Familial vasculitides: granulomatosis with polyangitis and microscopic polyangitis in two brothers with differing anti-neutrophil cytoplasm antibody specificity

Abstract

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases. Although the aetiology of AAV is uncertain, it is likely that genetic and environmental factors contribute. We report the unusual case of two brothers presenting with AAV with differing clinical pictures and differing ANCA specificity. There is a recently identified difference in genetic risk factors associated with ANCA specificity, making it surprising that first-degree relatives develop AAV with differing clinical and serological features. Our report illustrates the complex aetiology of AAV and suggests that further research on the interaction of genetic and environmental factors is needed.

Familial Association of Granulomatosis With Polyangiitis: A Case-Based Review of Literature

“…Renal biopsy showed pauci-immune crescentic glomerulonephritis. Surprisingly, he was diagnosed with MPA and treated with steroids, rituximab, and cyclophosphamide, which resulted in remission [ 11 ]. Similarly, Hay et al reported on two siblings with GPA, both with renal and pulmonary involvement [ 12 ].…”

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Update: Genetic Pathogenesis

“…Environmental factors, including silica exposure, bacterial or viral infections, and drugs suggest an association with the occurrence and relapse of AAV (6). Familial studies and genetic association studies have demonstrated that AAV has a background of genetic susceptibility (7)(8)(9). It has been estimated that 20% of AAV risk is due to genetic factors (10).…”

Pathogenesis and pathology of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis

“…Although very few cases of familial AAV have been reported, there have been various genetic studies including genome-wide association studies (GWASs) that have identified single nucleotide polymorphisms (SNPs) related to susceptibility. GWASs have also suggested some differences between the three AAV subsets or in geography [ 8 , 9 ]. A GWAS on United Kingdom patients revealed obvious genetic differences in GPA and MPA, and the genetic association was stronger in classification by ANCAs compared to classification by clinical presentation [ 10 ].…”