| Title | Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. | | Author(s) | Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA | | Institution | Naomi Berrie Diabetes Center and the Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York 10032, USA. kh318@columbia.edu | | Source | N Engl J Med 2002 May 30; 346(22):1692-8. | | MeSH | Adolescent
Adult
Antibodies, Monoclonal
Antigens, CD3
C-Peptide
CD4-CD8 Ratio
Child
Cytokines
Diabetes Mellitus, Type 1
Female
Hemoglobin A, Glycosylated
Humans
Lymphocyte Count
Male
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
| | 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--hOKT3gamma1(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 hOKT3gamma1(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. | | Language | eng | | Pub Type(s) | Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
| | PubMed ID | 12037148 |
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