Transporter-associated with antigen processing genes in primary IgA glomerulonephritis

Summary: Transporter-associated with antigen processing (TAP1 and TAP2) gene products are involved in the transport/processing of self-peptides from cytosol into endoplasmic reticulum (ER). In ER, these peptides associate with human leucocyte antigen (HLA)-class I molecules for further presentation at cell surface. Deficient processing and/or presentation could lead to altered self-tolerance resulting in autoimmunity. We studied TAP1 and TAP2 genes and genotypes frequencies in 49 controls and in 101 patients with primary IgA nephritis (IgAN). the patients were divided into two groups: 45 patients with end-stage renal failure (ESRF) and 56 patients with normal kidney function (NKF). DNA was extracted from peripheral blood and amplified by double amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) using appropriate primers for the two point-mutations on TAP1 genes and for the three point-mutations on TAP2 genes, which are the basis of TAP polymorphism. We have found a weak association between TAP2-p379-VAL/ILE genotype and total-IgAN (24%vs 12% in controls; P= 0.05). However, the analysis of a subgroup of IgAN patients bearing HLA-B35 antigen, a former poor prognosis marker, disclosed an association between the TAP2-1993Ntd-Guanine variant (coding for TAP2-p665-ALA): 31% in B35-ESRF-IgAN subgroup vs 6% in controls (P=0.04) and 13% in B35-NKF-IgAN (P=NS). the complexity of immunogenetic studies in IgAN is further increased by the existence of two opposite pathological subgroups: normal glomerular basement membrane (GBM) thickness vs thin-GBM. There was a complex relation in IgAN between this TAP2 variant and the following parameters: ESRF, HLA-B35, and normal-GBM. Further investigations are therefore needed.