The same HLA-DQ alleles determine either susceptibility or resistance to different coxsackievirus-mediated autoimmune diseases.
An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA1*0102, DQB1*0602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA1*0301, DQB1*0302), seem unable to sustain the immune attack against the heart.
Luppi
P
P
Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pennsylvania, USA.
Alexander
A
A
Bertera
S
S
Noonan
K
K
Trucco
M
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000821:virology; D004198:Disease Susceptibility; D029822:Enterovirus B, Human / Q000276:immunology*; D005260:Female; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D006683:HLA-DQ Antigens / Q000235:genetics*; D006367:HeLa Cells; D006321:Heart / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000821:virology; D010179:Pancreas / Q000821:virology; D018089:Superantigens; D014709:Vero Cells
D006683:HLA-DQ Antigens; D018089:Superantigens