Interleukin-1 receptor antagonist allele: Is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy?

Interleukin-1 receptor antagonist allele: Is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy? Henoch-Schönlein purpura nephritis (HSPN) is a multi-organ systemic vasculitis, which shares many clinical, histological and immunological features with IgA nephropathy (IgAN). To address whether these two diseases have a common genetic background, the polymorphism of the variable number tandem repeat (VNTR) of IL-1 receptor antagonist (IL-1ra) gene has been analyzed using PCR in patients diagnosed with HSPN (N = 43) and IgAN (N = 97), together with normal controls (N = 98) and patients with acute post-infectious glomerulonephritis (APGN), under the concept that IL-1 might play an important role in mediating pathogenesis of vasculitis and glomerulonephritis. It was found that the allele frequency and carriage rate of the interleukin-1 receptor antagonist allele (IL1RN*2) of the IL-1ra gene increased significantly in HSPN patients as compared to IgAN (P < 0.01), APGN (P < 0.05) and normal subjects (P < 0.01). Interestingly, varied carriage rates of IL1RN*2 were found among various groups of IgAN patients presenting with different clinical manifestations. The carriage rate of IL1RN*2 was significantly higher in patients with recurrent gross hematuria than other groups of IgAN patients (P < 0.01). Furthermore, although the carriage rate of IL1RN*2 was higher in HSPN (46.5%) than average IgAN patients (26.8%; P < 0.01), there was no significant difference in the carriage rate of IL1RN*2 between HSPN and those IgAN patients with recurrent gross hematuria (42.8%1 P > 0.05). It suggested that the IL1RN*2 allele might be a genetic marker shared by HSPN and a special group of IgAN patients with recurrent gross hematuria. Our preliminary observation provided a genetic evidence to support the hypothesis that HSPN and certain subgroup of IgAN are closely related diseases. Such an association of the gene polymorphism of IL-1ra between HSPN and IgAN with recurrent gross hematuria might serve as a key to explore their pathogenesis and eventually a specific intervention