Effect of anti-LFA1 (CD11a) monoclonal antibodies in acute rejection in human kidney transplantation.
A murine IgG1 monoclonal antibody, 25-3 (Immunotech, France), directed against the alpha chain (CD11a) of the human LFA1 molecule was used in the treatment of 7 histologically documented first acute rejection in first kidney transplantations under cyclosporine. Four patients (group I) received 20 mg/day for 2 days and 10 mg/day for 8 days of 25-3 MoAb. One developed Quincke's edema after the first injection of 25-3 and was immediately withdrawn from the study. In 2 patients, whose serum creatinine continued to increase, 25-3 MoAb was replaced by steroids, followed by ALG after 3 and 4 days of treatment, respectively. In the last case, rejection was reversed by 25-3 MoAb alone. As the clinical response of rejection to 25-3 was poor, another group of 3 patients (group II) was treated with 25-3 at a dose of 40 mg/day for 2 days, 20 mg/day for 2 days, and 10 mg/day for 6 days, but 25-3 was still unsuccessful in reversing acute rejection, and rescue treatment was initiated between days 5 and 8 in all cases. MoAb tolerance was excellent in 3 patients. With the exception of the one case of Quincke's edema, only minor side effects were noted in the last 3 recipients. 25-3 MoAb serum trough levels peaked between 1.5-3.5 micrograms/ml at day 3 in group I and between 2-9 micrograms/L at day 2 in group II. Surprisingly, only one patient, in group I, exhibited a borderline IgG immune response against 25-3. These findings suggest that the 25-3 anti-CD11a MoAb is ineffective in controlling the course of acute rejection in kidney transplantation. However as already reported for another anti-LFA1 or with an anti-CD4 MoAb in mouse, 25-3 would be the first example in humans of a MoAb that does not elicit a strong immune response against its own determinants. This property might have important applications if 25-3 can prevent rejection in a prophylactic protocol or block the immune response against other MoAbs.
Le Mauff
B
B
Service de Néphrologie et d'Immunologie Clinique, C.H.R.U. Nantes, France.
Hourmant
M
M
Rougier
J P
JP
Hirn
M
M
Dantal
J
J
Baatard
R
R
Cantarovich
D
D
Jacques
Y
Y
Soulillou
J P
JP
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D000917:Antibody Formation / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1