Serial monitoring of T-cell subset ratios with monoclonal antibodies in steroid- and antithymocyte globulin-treated patients with renal allotransplants

Abstract

Sequential changes in T-cell subsets or their ratios were employed to predict severity of rejection crises and to identify those patients who might require future antirejection therapy. Forty-two percent of the transplant recipients had a pretransplant OKT4:8 ratio in the range of 1.3 ± 0.5. By contrast, only 11% had a OKT4:8 ratio of 2.9 or greater. Examination of the entire study group demonstrated that the mean OKT4:8 ratios fell ( P < 0.01) in the first week following the transplant procedure. All patients had at least one episode of acute rejection. There was a marked increase ( P < 0.05) in the OKT4:8 ratio between the first week value and the value immediately preceding (within 3 days) the start of the rejection episode which was 2.64 ± 0.27. The mean OKT4:8 ratio in the 15 patients leaving the hospital with a functioning transplant was 1.18 ± 0.35. Three months post-transplant, the OKT4:8 ratio was 1.98 ± 0.39 in the 12 patients with functioning allografts. This value was not different from those patients' initial pretransplant values. Clinically, the rejection episodes could be divided into two groups based on their response to intravenous methylprednisolone therapy. The first group ( n = 9) had milder rejection crises which responded rapidly to administration of one course of methylprednisolone. The second group of patients ( n = 9) were also treated initially with methylprednisolone, to which they did not respond, and subsequently received antithymocyte globulin in an attempt to control their ongoing rejection crises. Following the transplant procedure, the OKT4:8 ratio decreased in patients who were destined to have steroid-responsive rejection episodes ( P < 0.01). The OKT4:8 ratio however, failed to fall in those who required ATG for control of their transplant rejection episodes. The onset of rejection episodes was associated with an increase in OKT4:8 ratio in both groups. Following steroid administration, two patterns of OKT4:8 cell responses were observed. Those in whom renal function improved demonstrated a decline in OKT4:8 ratio from 2.4 ± 0.4 to 1.4 ± 0.4 ( P < 0.05). However, no change occurred in the OKT4:8 ratios with steroid therapy (2.6 to 2.4 ± 0.33, P > 0.05) in individuals in whom the serum creatinine concentration failed to decline. The patients who failed to respond to steroid therapy were treated with antithymocyte globulin (ATG). OKT4:8 ratios dropped from an initial value of 2.8 ± 0.38 at the time of initiation of ATG therapy to 0.85 ± 0.17 at the end of ATG therapy. Three months after ATG therapy, the OKT4:8 ratios returned to normal. Thus, it was demonstrated that early sequential T-cell subset ratio monitoring could predict periods of rejection.