What (if any) link has been established between the Coxsackie B virus and the development of diabetes? My oldest daughter is eight years old and was diagnosed a year ago. My two-and-one-half year old son had lesions in his mouth caused by the Coxsackie B virus when he was six months old. I recently read a study that mentioned the Coxsackie B virus as producing the same GAD proteins found in people with diabetes, and I’m just wondering what implications this might have for my son.

To start with the simple bit, if your eight year old daughter is known to have Type 1A antibody positive autoimmune diabetes then her brother has approximately a 5% chance of developing the same form of diabetes. After he becomes four years old you might like to consider getting an antibody test done (telephone 1-800-425-8361) and in the unlikely event that it is positive enrolling him in the National DPT-1 trial of small doses of insulin subcutaneously or orally to prevent insulin dependence.

There is indeed a relationship between Coxsackie B infection and type 1A diabetes. If you are up to some technical jargon and have access to a medical library, you might like to look at a report by Vreugdenhill GR, in J.Med.Virol. 59:256, 1999 and Karlsson MG, in Acta Diabetol. 35:137, 1998 for an account of the scientific basis for this relationship. More comfortably, you could search under ‘Coxsackie B and GAD’ in PubMed.

To try to summarise it all briefly: type 1A diabetes is evoked by both a genetic and an environmental component. In the former a macrophage white blood cell that has a certain pattern of HLA protein on the surface may combine with a protein fragment that, in turn, stimulates the activation of CD4 lymphocytes to destroy beta cells. In diabetes, the protein fragments that have been most likely to provide this stimulus have been fragments of human insulin or GAD. In the Coxsackie B4 virus, there is a similarity between a protein called CVB4 and a human GAD fragment called GAD65. It seems quite logical, therefore, that a Coxsackie B4 infection could start the autoimmune process. However, other studies have shown that the antibodies to CVB4 are different from those to GAD65 and have consequently suggested that these two proteins have different aptitudes for inducing the destructive Th1 type of lymphocyte response against beta cells. The picture is further complicated by the association of two autoimmune conditions in which there are high titers of perhaps two different antiGAD antibodies — namely, the stiff man syndrome and type 1 diabetes.

At the moment, the balance of opinion is that the specific antigen is a piece of the B chain of human insulin rather than CVB4. Nonetheless, there is a proposal to use a GAD65 vaccine to try to delay insulin dependence. The DPT-1 trial is already using insulin as a vaccine to induce a protective Th2 response in lymphocytes rather than the toxic Th1 response. In a further refinement, the 9-23 fragment of the B chain of insulin is also going to be tried as a ‘vaccine’.

DOB