Issue 144 Item 3 Protein Processing Problems May Contribute to Diabetes

Study of cells derived from identical twins indicates that diminished expression of an important chaperone protein may be involved in the development of type I diabetes. That, according to researchers in the January issue of the Journal of Immunology.

Dr. Denise L. Faustman reported that, "it has been known for years that identical twins have little chance of both being affected with autoimmunity, always less than 50% and sometimes as low as 15%. This is a big clue that possible markers of disease and disease causing differences are not at the gene level but the protein level."

To investigate, Dr. Faustman of Massachusetts General Hospital, Charlestown, and colleagues studied B cell lines derived from pairs of identical twins discordant for type I diabetes.

MHC class II protein-associated defects found exclusively in cells from twins with autoimmunity included increased rates of transport to and subsequent turnover at the cell surface, a reduced display of antigenic peptides at the cell surface and inadequate glycosylation. These appeared to be secondary to reduced expression of an isoform of the invariant chain, namely the protein Ii p35.

"Minor changes in the amount of this chaperone protein impacted a critical step for prevention of auto-reactivity," Dr. Faustman continued. "The human diabetic twin made less of this protein and this caused major trafficking problems of the proteins in the white blood cells of only the diabetic twin."

She added that while therapy is "a long way off…many efforts worldwide are now being made on methods of altering ‘translation’ and ‘trafficking’ differences in cells." This new research focus on proteins might be compared "to the huge efforts on genes from many years ago." J Immunol 2003;170:620-627