TRANSPORTER-ASSOCIATED WITH ANTIGEN-PROCESSING GENES IN PRIMARY IGA GLOMERULONEPHRITIS

Transporter-associated with antigen processing (TAP1 and TAP2) gene pr oducts are involved in the transport/processing of self-peptides from cytosol into endoplasmic reticulum (ER). In ER, these peptides associa te with human leucocyte antigen (HLA)-class I molecules for further pr esentation at cell surface. Deficient processing and/or presentation c ould lead to altered self-tolerance resulting in autoimmunity. We stud ied TAP1 and TAP2 genes and genotypes frequencies in 49 controls and i n 101 patients with primary IgA nephritis (IgAN). The patients were di vided 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 appropriat e 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 a nd total-IgAN (24% vs 12% in controls; P = 0.05). However, the analysi s of a subgroup of IgAN patients bearing HLA-B35 antigen, a former poo r prognosis marker, disclosed an association between the TAP2-1993Ntd- Cruanine variant (coding for TAP2-p665-ALA): 31% in B35-ESRF-IgAN subg roup vs 6% in controls (P = 0.04) and 13% in B35-NKF-IgAN (P = NS). Th e complexity of immunogenetic studies in IgAN is further increased by the existence of two opposite pathological subgroups: normal glomerula r basement membrane (GEM) thickness us thin-GEM. There was a complex r elation in IgAN between this TAP2 variant and the following parameters : ESRF, HLA-B35, and normal-GBM. Further investigations are therefore needed.