The role of macrophage cytophilic antibiodies in kidney transplant patients.

Previous studies in our laboratory suggest that macrophage cytophilic antibodies (M.C.A.) specific for allogeneic determinants could be detected in rat skingrafted from appropriate strain of rat.In this present study, macrophage cytophilic antibody titers were followed with opsonization test which were carried out using peripheral lymphocytes of the kidney donor, macrophage monolayers cultured in Falcon trays from peripheral monocytes of healthy volunteers and serial test serum of the transplant recipient, without use of complement. Modified Terasaki microcytotoxicity test was also done stimutaneously.Twenty-six kidney transplant recipients who received grafts from twentyseven Living-Related-Donors have been followed for one month to two years and three months. Average follow up period is 11.6 months at the present time.Twelve out of twenty-seven transplants did not show any positive cytotoxicity. In this group, six patients have never experienced clinical rejection episodes. And other six patients did experience rejection episodes but all recovered from them except one. Eleven out of twelve kidneys are now functioning and ten patients have normal serum creatinine level. Mean serum creatinine of the eleven patients with functioning grafts is 1.17±0.25 mg/dl.Other twelve transplants developed positive M.C.A. against kidney donors' lymphocytes during post-transplant course. All of the twelve patients experienced moderate to severe rejection episodes. Three of them lost their kidney grafts. And nine out of twelve kidney grafts are now functioning and only three patients have normal serum creatinine. Mean serum creatinine level of the nine patients is 1.77±.50 mg/di. Of the twelve patients who showed positive M.C.A. in this group only one developed positive cytotoxicity after he rejected the kidney.Cytotoxicity test was negative before surgery in all twenty-seven transplants. But there were three patients who had Positive M.C.A. against kidney donors' lymphocytes before transplant surgery, already. All three recipients suffered from severe acute rejection crisis. And two have rejected their kidney grafts. One of them died of Pneumocystis carini infection with gram negative septisemia following repeated vigorous anti-rejection treatments. In this group, two patients developed positive cytotoxicity only after they rejected kidney or even after transplant nephrectomy.The tentative conclusion at this time is that detection of M.C.A. with opsonization test seems to represent much more sensitive indicater of the immune reactive state between donor and recipient in human kidney allo-transplantation. While no pre-transplant serum showed positive cytotoxicity, three pretransplant serum showed positive M.C.A. to kidney donors' lymphocytes and all three patients suffered from severe acute (not HYPER-ACUTE) rejection and two of them lost grafts.By eliminating these presensitized pairs using this test system, it may be possible to improve clinical results of kidney transplantation.Also, it might be able to differentiate clinical rejection episode which is dominated by antibody mediated cellular immunity from humoral antibody prodominated one.A part of this paper was read at the sixth annual meeting of American Society of Nephrology, November 1973 at Washington D.C and was supported by NIH grants (No. 9642 & No. 9947).