The Heterogeneous Epitope(s) Of Anti-GBM Autoantibodies In Sera From Chinese Patients With Anti-GBM Disease

Background and aims:Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease induced by anti-GBM autoantibodies. The main target antigen of anti-GBM autoantibodies is non-collagen domain 1 of theα3 chain of type IV collagen [a3(IV)NCl].It is well known that the anti-GBM autoantibodies recognized cryptic conformational epitopes within a3(IV)NCl.However, early studies suggested that sera from some patients might also recognize exposed epitope(s) on GBM, but the clinical significance was not clear. The present study is to investigate the heterogeneity of epitopes recognized by anti-GBM autoantibodies in sera from a large cohort of Chinese patients with anti-GBM disease; their clinical significance was further studied.Methods:The present study included 108 patients with anti-GBM disease who were diagnosed in our hospital, between Jan 1991 and May 2009, with complete clinical and renal pathological data. Sera or plasma exchange of the patients at presentation were used to incubate with cryostat section of normal human renal tissue for indirect immunofluorescence (ⅡF) assay. The cryostat sections of normal renal tissue were pre-treated by 6M urea to unmask cryptic epitopes, and untreated cryostat sections were used to detect natural exposed epitopes. The sera were diluted from 1:2 to 1:512 to determine titers of anti-GBM autoantibodies.Patients with anti-GBM autoantibodies against cryptic or exposed epitopes were further stratified, their clinical and pathological associations were analyzed. Result:Sera from all the 108 patients could recognize cryptic epitopes on normal renal tissue (urea treated section).IIF showed IgG linear staining along GBM. However, sera from 56/108 patients (group A) could also recognize exposed epitopes on normal renal tissue (untreated section), sera from the rest 52/108 patients (group B) could not recognize exposed epitopes. In urea treated condition, the average titer of anti-GBM autoantibodies from sera of patients in group A were significantly higher than that in group B (p<0.01),ANCA-positive patients in group A were significant less than that in group B (p<0.01).There was no significant difference between the two groups in regard of other clinical data (including serum creatinine) at presentation and renal histopathologic data.Conclusion:Anti-GBM autoantibodies from some patients with anti-GBM disease could recognize natural exposed epitopes, however, their anti-GBM titers for cryptic epitopes were higher than that of those recognizing cryptic epitopes only and the prevalence of serum ANCA was significantly less.