ANALYSIS OF THE RELATIONSHIP BETWEEN CHIMERISM AND THE ALLOGENEIC HUMORAL RESPONSE

Background. Persistence of antigens has been suggested to play a role in two opposing immunological phenomena: tolerance and memory. Therefo re, we studied the impact of chimerism on alloreactive antibody (allo- Ab) production in kidney transplant patients. Methods. Thirty-five fem ale renal transplant recipients of male donor organs were classified i nto the following groups: group 1, 13 sensitized uremic patients on di alysis; group 2, 5 nonsensitized uremic patients on dialysis; group 5, six sensitized patients experiencing graft rejection (3 acute vascula r, 1 acute cellular, and 2 chronic); and group 4, 11 nonsensitized wit h functioning allografts (9 with good function, 1 with acute cellular rejection, and 1 with chronic rejection). Mean duration of dialysis af ter graft failure was similar in groups 1 (56+/-29.7 months) and 2 (41 .8+/-42.4 months), as was dialysis efficiency, Chimerism was measured indirectly in the peripheral blood lymphocytes by polymerase chain rea ction amplification of a specific Y chromosome DNA gene sequence with a detection sensitivity Limit of 1 male cell per 1 million female cell s. Allo-Ab production was measured by the PRA-STAT enzyme-linked immun osorbent assay (Sangstat) method. Results. Chimerism was observed in 6 0% of groups 1 and 2, 83% of group 3, and 82% of group 4. Among all gr oups, graft existence, irrespective of its function, positively predic ted chimerism in 92% with a sensitivity of 88% and a specificity of 78 %. In group 3, all three patients with acute vascular rejection had ch imerism and donor-specific allo-Abs, In group 4, eight of the nine pat ients with no rejection had chimerism. Conclusion, Chimerism relates t o persistence of allogeneic stimulus irrespective of its function. Chi merism did not confer protection against allo-Ab production or vascula r rejection, and its existence was not crucial for sustenance of allo- Ab production.