|Professor Irun R. Cohen|
The Helen and Morris Mauerberger Professor of Immunology
DiaPep277 Peptide and Type 1 Diabetes
Raz I., Elias D., Avron A., Tamir M., Metzger M., Cohen I.R.
-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): A randomized, double-blind, phase II trial. The Lancet, 2001; 358: 1749-53.
At the practical level, this paper shows that autoimmune destruction of beta cells in patients with newly diagnosed type 1 diabetes can be arrested by the administration of DiaPep277, a peptide fragment of the 60kDa heat shock protein molecule. Three subcutaneous injection of the peptide, 1 mg each in an oil vehicle, were effective. The optimal dose of peptide and the most effective schedule of injections remain to be worked out. Nevertheless, the confirmation of effectiveness and safety in continuing trials would indicate that immunologically specific treatment of autoimmune disease is feasible.
At the theoretical level, these results serve as a proof-of-concept in the controversy between contending theories regarding the basic organization of the immune system. The classical clonal selection theory holds that:
These tenets of classic clonal selection are not compatible with the findings reported in the paper. On the contrary, the success of the clinical trial of therapeutic peptide vaccination is compatible with the homunculus concept of autoimmunity. This theory includes the following ideas:
- Self-non-self discrimination is the aim of the immune system;
- Autoimmunity is deleted from the healthy repertoire of antigen receptors;
- Autoimmunity arises by accident;
- Autoimmune disease therapy requires blocking self-recognition, or removal of self-recognizing lymphocytes.
- The aim of the immune system is not to discriminate self from non-self, but to organize inflammation in a way that maintains, heals and, where possible, regenerates damaged cells and tissues; the healthy system is continuously responding to self.
- The healthy repertoire includes a high frequency of lymphocytes that recognize key self-antigens: the immunological homunculus.
- Autoimmune diseases arise from a failure of normal regulation, and the resulting diseases are predictably associated with collectives of particular self-antigens.
- The natural cure to autoimmune disease is to activate and reinstate the regulatory mechanisms built into the homunculus.
The paper demonstrates that a single peptide can indeed activate regulation; the immune system is best controlled by supplying the immune information the system is organized to seek. The immune system is a cognitive system.
For further reading see:
- Cohen I.R. Tending Adam's Garden: Evolving the Cognitive Immune Self.
Academic Press, New York, 2001.
- Schwartz M, Cohen I.R. Autoimmunity can benefit self-maintenance.
Immunol. Today, 2000; 21: 265-8.
- Cohen I.R. Discrimination and Dialogue in the Immune System. (2000)
Seminars in Immunology 12: 215-219; 269-271; 321-323.
- Cohen I.R. (1992) The cognitive principle challenges clonal selection.
Immunol. Today 13: 441-4.
- Cohen I.R. (1992) The cognitive paradigm and the immunological homunculus.
Immunol. Today 13: 490-4.