COMPARATIVE NEPHRITOGENICITY OF 2 MONOCLONAL-ANTIBODIES THAT RECOGNIZE DIFFERENT EPITOPES OF RAT THY-1.1 MOLECULE

The pathophysiological role of the Thy-1.1 molecule expressed on rat m esangial cells with regard to mesangial cell dysfunction and injury re mains unknown. The mechanism of Thy-1.1-associated injury has now been investigated with two monoclonal antibodies, 1-22-3 and OX7, that rec ognize different epitopes of Thy-1.1. Mesangiolysis and mesangial cell proliferation were more marked in rats injected with 1-22-3 than in t hose treated with OX7, Immunostaining for rat complement component C3 and also C9 was similar in the kidneys of rats 1 h after injection of either antibody, Alpha smooth muscle actin was first detected 3 days a fter injection of 1-22-3 and peaked on day 5; type I collagen staining showed a mesangial pattern on days 5 and 10. The staining for alpha s mooth muscle actin and type I collagen was less intense in OX7-treated rats than in the 1-22-3-injected rats, The amounts of mRNAs encoding collagen types I and III peaked 5 days after injection of 1-22-3 and 1 0 days after injection of OX7, Rats injected with 1-22-3 developed pro teinuria that was already marked on day 1 and peaked at 150 mg/day on day 3, whereas OX7 induced a low grade of proteinuria with large inter individual variability on day 3, Immunostaining for rat C3 in the norm al rat kidneys, incubated in vitro with 1-22-3 or OX7 followed by incu bation with normal rat fresh serum as a complement source, as well as the levels of serum complement activity, CH50, 30 min after injection of 1-22-3 or OX7 were similar, suggesting that the difference in the n ephritogenicity of these two antibodies is not attributable to a diffe rence in their complement-fixing activities, but rather may result fro m the difference in epitope specificities, The epitope recognized by 1 -22-3 thus appears to be important in the initiation and progression o f antibody-induced nephritis.