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Immune Tolerance

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Clinical Studies

NIAID, along with the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation International, cosponsors the Immune Tolerance Network (ITN), an international consortium of more than 80 investigators in the United States, Canada, Europe, and Australia dedicated to the clinical evaluation of novel, tolerance-inducing therapies for autoimmune diseases, asthma and allergic diseases, and transplant rejection. ITN conducts integrated studies on the mechanisms that underlie immune tolerance and develops markers and assays to measure the induction, maintenance, and loss of tolerance in humans. The network has established several state-of-the-art core facilities and has supported 18 approved clinical protocols as well as several additional studies of the immune mechanisms involved in tolerance.

ITN is currently involved in the following areas of clinical research:

  • Allergy
  • Asthma
  • Diabetes
  • Islet cell, kidney, and liver transplantation
  • Bone marrow transplantation
  • Multiple sclerosis (MS)
  • Psoriatic arthritis
  • Systemic lupus erythematosus

Examples of active ITN clinical research studies include

  • A Phase I trial to analyze and monitor the safety of immunization with a fragment of the human insulin B chain in subjects newly diagnosed with Type 1 diabetes; the hope is that this “autoimmunization” therapy will increase the immune tolerance of insulin-producing cells.
  • A pilot study to evaluate the safety and efficacy of a treatment regimen to induce tolerance in kidney transplant recipients. In this study, patients will receive low-dose steroid-free immunosuppression, two donor stem cell infusions, and an antibody called Campath-1H, which selectively eliminates immune system T cells involved in organ rejection. Treatment will be withdrawn after 1 year and the patients followed to see if long-term tolerance has been achieved.
  • A Phase I study in 16 patients with relapsing-remitting MS to assess the safety of one dose of CTLA4-IgG4m, an antibody that may block a pathway that allows the immune system to attack nervous system tissue.
  • A Phase II multicenter trial to evaluate the lipid-lowering drug atorvastatin in patients at high risk of developing MS.

Tolerance assays—tests and procedures to monitor patient responses to tolerance therapies—are critically needed to better evaluate tolerance-inducing therapies during and after clinical trials. ITN has therefore established a set of core laboratories to develop assays for the induction, maintenance, or loss of immune tolerance. These core facilities carry out microarray analyses of gene expression, develop analytic tools for clinical and scientific datasets from ITN-sponsored trials, and conduct enzyme-linked immunospot (ELISPOT) assay analyses of protein expression and cellular assays for T cell reactivity.

Examples of current ITN efforts to develop mechanistic assays include

  • Development of antigen-specific assays for donor-specific tolerance in renal transplant recipients
  • Cytokine production in children with preclinical and clinical Type 1 diabetes
  • Identification and mechanistic investigations of tolerant kidney transplant patients

More information on ITN’s mission and research is available at

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Last Updated March 28, 2006