Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
N Engl J Med. 2002 May 30;346(22):1692-8.

Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus.

Author information

  • 1Naomi 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

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.

Comment in

PMID:
12037148
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Write to the Help Desk