Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch–Schönlein purpura susceptibility and severity

Abstract

Henoch–Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP. Methods: Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 −2518C/T, RANTES/CCL5 −403C/T, and RANTES/CCL5 −28C/G with HSP in 85 HSP patients and 136 healthy controls. Results: Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 −2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45–7.59) and 1.78 (1.20–2.64), respectively. The RANTES/CCL5 −28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 −403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44–12.99), adjusted for sex and age and the other two SNP genotypes. Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

Keywords

• chemokine
• Henoch–Schönlein Purpura (HSP)
• MCP1/CCL2
• polymorphism
• RANTES/CCL5