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Previous Volume 346:1692-1698 May 30, 2002 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Gale, E. A.M. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Type 1 diabetes mellitus is a chronic autoimmune disease caused by the pathogenic action of T lymphocytes on insulin-producing beta cells. Previous clinical studies have shown that continuous immune suppression temporarily slows the loss of insulin production. Preclinical studies suggested that a monoclonal antibody against CD3 could reverse hyperglycemia at presentation and induce tolerance to recurrent disease.

Methods We studied the effects of a nonactivating humanized monoclonal antibody against CD3 — hOKT31(Ala-Ala) — on the loss of insulin production in patients with type 1 diabetes mellitus. Within 6 weeks after diagnosis, 24 patients were randomly assigned to receive either a single 14-day course of treatment with the monoclonal antibody or no antibody and were studied during the first year of disease.

Results Treatment with the monoclonal antibody maintained or improved insulin production after one year in 9 of the 12 patients in the treatment group, whereas only 2 of the 12 controls had a sustained response (P=0.01). The treatment effect on insulin responses lasted for at least 12 months after diagnosis. Glycosylated hemoglobin levels and insulin doses were also reduced in the monoclonal-antibody group. No severe side effects occurred, and the most common side effects were fever, rash, and anemia. Clinical responses were associated with a change in the ratio of CD4+ T cells to CD8+ T cells 30 and 90 days after treatment.

Conclusions Treatment with hOKT31(Ala-Ala) mitigates the deterioration in insulin production and improves metabolic control during the first year of type 1 diabetes mellitus in the majority of patients. The mechanism of action of the anti-CD3 monoclonal antibody may involve direct effects on pathogenic T cells, the induction of populations of regulatory cells, or both.

Source Information

From the Naomi Berrie Diabetes Center and the Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York (K.C.H., E.P.-R., L.T.); Pacific Northwest Research Institute, Seattle (W.H.); the University of Chicago, Chicago (J.A.A.); the University of Utah, Salt Lake City (D.D.); the Departments of Pediatrics (S.E.G.) and Medicine (J.A.B.), University of California at San Francisco, San Francisco; the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md. (D.M.H.); and the R.W. Johnson Pharmaceutical Research Institute, Raritan, N.J. (D.X., R.A.Z.).

Address reprint requests to Dr. Herold at Columbia University, 1150 St. Nicholas Ave., New York, NY 10032, or at kh318{at}columbia.edu.

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Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus
Killestein J., Herold K. C., Bluestone J. A.
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N Engl J Med 2002; 347:1116-1117, Oct 3, 2002. Correspondence

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