EARLY RENAL GRAFT DYSFUNCTION - THE ROLE OF PREFORMED ANTIBODIES TO DR-TYPED LYMPHOBLASTOID CELL-LINES

Diverse pathogenetic factors may lead to the complex syndrome of early graft dysfunction, an important determinant of later renal graft outc ome. That humoral factors could play a prominent role in the developme nt of the syndrome was suggested by the capillary deposition of comple ment fragment C4d in about 50% of graft biopsies. This study investiga tes whether the presumed classical activation of complement is derived from preformed antibodies that would possibly react against endotheli al HLA-class II molecules. Such antibodies were detectable by flow cyt ometry using a representative collection of 11 DR-typed lymphoblastoid cell lines (LCL) as targets. Simultaneous discrimination between comp lement-activating and -nonactivating antibodies was achieved by two-co lor FAGS analysis. Using this method, 44 out of 86 pretransplant serum samples from recipients with early dysfunction showed reactivity agai nst LCL (18 complement-activating, 14 nonactivating, 12 complement-act ivating non-IgG). Conventional panel-reactivity was observed in 20 ser a only (14 also LCL-reactive), Evaluation of corresponding graft biops ies revealed that capillary C4d was associated with LCL (P=0.018) and panel reactivity (P=0.015) alone and in combination (P=0.001; Pearson' s chi-square test). Thirteen subsequent graft losses within one year w ere observed in the LCL-reactive group as compared with seven losses i n the nonreactive group (panel-reactive: 7; nonreactive: 13). Thus, me asurement of LCL-reactive antibodies in prospective transplant recipie nts improves the assessment of an individual immunological risk, The r esults further demonstrate that preformed antibodies do not simply ref lect the enhanced overall immune reactivity of certain recipients but rather act locally in vivo, thus emphasizing the role of humoral facto rs in the development of early graft dysfunction.