Paul E. Lacy

No evidence for serological autoimmunity to islet cell heat shock proteins in insulin dependent diabetes.

Recent studies in nonobese diabetic mice have implicated the autoimmune destruction of pancreatic islet cells with immunity to a beta cell protein cross-reactive to Mycobacterium tuberculosis heat shock protein 65 (hsp 65). Therefore, our studies examined serological immunity to islet cell hsp in humans with insulin-dependent diabetes (IDD). Heat shock of human islet cells in vitro markedly increased the synthesis of proteins of 72,000, 75,000, and 90,000 Mr. No autoantibodies reactive to these hsp, nor to the constituently expressed islet cell hsp 65 protein (identified as 60,000 Mr) were observed in IDD patients. The islet cell 64,000-Mr autoantigen and hsp 65 proteins were physiologically and immunocompetitively distinct. These experiments do not support the hypothesis that IDD in humans is associated with autoimmunity to islet cell heat shock proteins.

Prevention of rejection of islet allografts and xenografts without continuous immunosuppression of the recipients

The objective of transplanting islets into diabetic patients is to accomplish the transplants early in the course of diabetes with the hope that these transplants will prevent the development of the complications of diabetes such as blindness, renal failure and early onset of artherosclerosis. This objective places islet transplantation in a different setting as compared to transplantation of whole organs such as the heart, liver or kidney. The whole organ transplants are done in patients who are acutely ill and, in the case of heart and liver transplants are needed to preserve the life of the patient. In contrast, diabetes mellitus is a chronic disease requiring decades to develop the complications of this disease. Thus, the use of islet transplantation in diabetes requires an approach which would prevent rejection of the islet transplants without the need for continuous immunosuppression of the patients. The reason for this is that chronic administration of immunosuppressive drugs could lead to serious toxic side effects that could be more devastating than the complications of the disease itself.