TITLE:
IL-4, IL-10 and TNF-α Polymorphisms in Idiopathic Membranous Nephropathy (IMN)
AUTHORS:
Mauro Giacomelli, Rajesh Kumar, Giacomo Tampella, Simona Ceffa, Mario Bontempelli
KEYWORDS:
Interleukin-Four, Tumor Necrosis Factor-α, Interleukin-Ten, Idiopathic Membranous Nephropathy, Immunoglobulin G Sub-Class 4
JOURNAL NAME:
Open Journal of Immunology,
Vol.5 No.5,
December
3,
2015
ABSTRACT: Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.