MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES IN GLOMERULAR-DISEASES

The identification of genes within the human major histocompatibility complex (MHC) class II region, which confer susceptibility of immune m ediated nephritis can help to understand the immunopathogenesis and in heritance of these diseases. Classically, this is performed using sero logical typing. The use of DNA technology in genotyping is more specif ic and would reveal greater polymorphism within this region. The MHC c lass II studies of IgA nephropathy (IgAN) and Goodpasture's disease ar e illustrative. We have shown that by the polymerase chain reaction (P CR) using sequence specific oligonucleotide (SSO) probing techniques, there was an increase of human leucocyte antigen (HLA) DQ7 in Caucasia n IgAN patients (71%) when compared with controls (27.8%). In a Chines e family of IgAN, all three siblings with IgAN were homozygous for DR1 2, DQ7, DQ alpha 1b. When we examined 79 Chinese IgAN patients, there was an increase in homozygous DQ7 in patients (16.4%) compared with co ntrols (5.7%). There was also a significant increase in frequency of D QA2 U allele in patients with chronic renal failure (66.9%) compared w ith patients with normal renal function (26.9%). Goodpasture's disease (GPD) was initially reported to be associated with HLA-DR2. With mole cular techniques, it was found that 75.5% of GPD had DR15 (a specifici ty of DR 2) when compared with controls (31%). The frequency of DR4 wa s also increased. Nucleotide sequences of these two alleles were ident ical to those previously published. Compared with derived amino acid s equences of expressed DR beta chains showed that the DR beta chains of DR15 and DR4 shared a six aminoacid motif from positions 26-31. An SS O detected this amino acid motif in 91.8% of GPD patients tested. Thus , this particular motif, which lies on the floor of the antigen bindin g groove, has a stronger association with GPD than an individual allel e, and may be of pathogenetic significance. It is therefore concluded that the study of MHC class II genes is important in the elucidation o f the pathogenetic mechanisms and possibly in the prediction of diseas e severity in glomerulonephritis.