N. Broeders et al., MYCOPHENOLATE MOFETIL, TOGETHER WITH CYCLOSPORINE-A, PREVENTS ANTI-OKT3 ANTIBODY-RESPONSE IN KIDNEY-TRANSPLANT RECIPIENTS, Journal of the American Society of Nephrology, 9(8), 1998, pp. 1521-1525
OKT3 monoclonal antibody, a murine IgG2a monoclonal antibody targeting
the T cell CD3 antigen, elicits a neutralizing humoral response in 20
to 50% of kidney transplant recipients when the concomitant immunosup
pression consists of CsA-Sandimmun (SAND) and azathioprine (AZA). In t
he present study, we investigated the impact of the newer agents, CsA-
Neoral (NEO) and mycophenolate mofetil (MMF) on OKT3 sensitization. Si
xty-two consecutive kidney transplant recipients received prophylactic
OKT3 (5 mg/d) from days 0 to 13, together with steroids. Concomitant
immunosuppression consisted of either AZA + SAND (n = 20), AZA + NEO (
n = 31), or MMF + NEO (n = 11). The following doses were used: AZA, 2
mg/kg per d from days 0 to 13, then 1 mg/kg per d; MMF, 2 g/d starting
on day 1; and CsA, either SAND or NEO, 6 mg/kg per d from day 6. At l
east two serum samples per month were available during the initial 3 m
o for each patient. IgG anti-OKT3 antibodies were first evaluated by e
nzyme-linked immunosorbent assay. Patients were considered sensitized
if their serum scored positive at a dilution greater than or equal to
1/1000. Peak titers of IgG anti-OKT3 antibodies and the incidence of p
atients harboring neutralizing anti-idiotypic antibodies were also det
ermined. A first reduction in OKT3 sensitization was seen in patients
receiving Neoral instead of Sandimmun (AZA + SAND: 10 of 20 [50%] pati
ents sensitized versus 6 of 31 [19%] in the AZA + NEO group; P = 0.03)
. This was probably related to the achievement of higher mean CsA trou
gh blood levels in the NEO group during the first month (253 +/- 44 ve
rsus 186 +/- 49 ng/ml in SAND patients). Peak antibody titers and the
proportion of patients with anti-idiotypic antibodies were similar in
the AZA + SAND and AZA + NEO groups. A further reduction in the sensit
ization rate was observed with the replacement of AZA by MMF (MMF + NE
O: 0% sensitized patients; P = 0.0013). It is concluded that the combi
nation of CsA-Neoral and MMF efficiently prevents sensitization agains
t OKT3.