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Autoantibodies in canine diabetes mellitus
A D VA N C E S
PAG E 5
AUTOANTIBODIES IN CANINE DIABETES MELLITUS Background Dogs with diabetes mellitus require insulin therapy early in the development of the disease and therefore are similar to humans with type 1 diabetes mellitus. Type 1 diabetes mellitus is believed to result from immune-mediated destruction of pancreatic beta cells. Human diabetics suffering from Type 1 diabetes demonstrate circulating autoantibodies against the 65 kDa isoform of glutamic acid decarboxylase (GAD65) or insulinoma antigen-2 (IA-2), or both.
PA G E 6
A D VA N C E S
Objectives To develop a radioimmunoassay to detect serum antibodies against recombinant canine GAD65 and IA-2, and to identify diabetic dogs showing serological evidence of autoantibodies to these pancreatic beta cell antigens.
Procedure Canine GAD65 and IA-2 were amplified by PCR from canine insulinoma DNA tissue and cloned into the vector. Recombinant 35S-methionine-radiolabelled canine GAD65 and IA-2 proteins were used in radioimmunoprecipitation assays to screen sera from 30 newly diagnosed diabetic dogs and 30 control dogs.
Results Four of 30 canine diabetic patients had significant GAD65 autoreactivity compared to controls, and 3 dogs were positive for autoantibodies to IA-2. Two diabetic dogs showed autoreactivity to both.
Author Conclusion Serological reactivity to GAD65 and IA-2 is present in a proportion of diabetic dogs, and in some of these, the pathogenesis of diabetes may be related to an autoimmune response to these antigens.
Inclusions Three figures, 1 table, 28 references.
Editor Annotation Canine diabetes clinically resembles human type 1 diabetes in that affected dogs are prone to develop ketoacidosis and require insulin for effective treatment. However, whether diabetes is due to shared pathophysiology in these species is unclear. For example, circulating autoantibodies directed against pancreatic islet antigens are commonly detected in human type 1 diabetics, but evidence for the same phenomenon in dogs is scanty. The study by Davidson et al. has shed new light on the presence of islet cell autoantibodies in canine diabetes. The authors examined newly diagnosed diabetic dogs for the presence of circulating autoantibodies against GAD65 and IA-2 proteins, which are also targeted in human type 1 diabetics. The assay used by Davidson et al. employed canine-specific proteins to capture autoantibodies, which improved assay specificity. Autoantibodies against 1 or both proteins were detected
in 5 of the 30 dogs tested, which suggests and immune component may be involved in diabetes pathogenesis, at least in some dogs. The finding that only about 15% of dogs had autoantibodies is not too surprising, considering the study population was unselected with respect to diabetes etiology. It is important to remember that while canine diabetes is a clinically homogeneous disorder, it is likely a heterogeneous disease with respect to pathogenesis. Further, despite the impression given by textbooks and review articles, the prevalence of autoimmunity in the overall population of canine diabetics is not known. Many questions remain to be investigated regarding the role of autoimmunity in the genesis of canine diabetes. The current study provides a useful starting point from which to pursue these questions. (TS) Davison LJ, Weenink SM, Christie MR, et al. Autoantibodies in GAD65 and IA-2 in canine diabetes mellitus. Vet Immunol Immunopathol (2008), doi:10.1016/j.vetimm.2008.06.016 (electronic version prior to publication).
PAG E 5
AUTOANTIBODIES IN CANINE DIABETES MELLITUS Background Dogs with diabetes mellitus require insulin therapy early in the development of the disease and therefore are similar to humans with type 1 diabetes mellitus. Type 1 diabetes mellitus is believed to result from immune-mediated destruction of pancreatic beta cells. Human diabetics suffering from Type 1 diabetes demonstrate circulating autoantibodies against the 65 kDa isoform of glutamic acid decarboxylase (GAD65) or insulinoma antigen-2 (IA-2), or both.
PA G E 6
A D VA N C E S
Objectives To develop a radioimmunoassay to detect serum antibodies against recombinant canine GAD65 and IA-2, and to identify diabetic dogs showing serological evidence of autoantibodies to these pancreatic beta cell antigens.
Procedure Canine GAD65 and IA-2 were amplified by PCR from canine insulinoma DNA tissue and cloned into the vector. Recombinant 35S-methionine-radiolabelled canine GAD65 and IA-2 proteins were used in radioimmunoprecipitation assays to screen sera from 30 newly diagnosed diabetic dogs and 30 control dogs.
Results Four of 30 canine diabetic patients had significant GAD65 autoreactivity compared to controls, and 3 dogs were positive for autoantibodies to IA-2. Two diabetic dogs showed autoreactivity to both.
Author Conclusion Serological reactivity to GAD65 and IA-2 is present in a proportion of diabetic dogs, and in some of these, the pathogenesis of diabetes may be related to an autoimmune response to these antigens.
Inclusions Three figures, 1 table, 28 references.
Editor Annotation Canine diabetes clinically resembles human type 1 diabetes in that affected dogs are prone to develop ketoacidosis and require insulin for effective treatment. However, whether diabetes is due to shared pathophysiology in these species is unclear. For example, circulating autoantibodies directed against pancreatic islet antigens are commonly detected in human type 1 diabetics, but evidence for the same phenomenon in dogs is scanty. The study by Davidson et al. has shed new light on the presence of islet cell autoantibodies in canine diabetes. The authors examined newly diagnosed diabetic dogs for the presence of circulating autoantibodies against GAD65 and IA-2 proteins, which are also targeted in human type 1 diabetics. The assay used by Davidson et al. employed canine-specific proteins to capture autoantibodies, which improved assay specificity. Autoantibodies against 1 or both proteins were detected
in 5 of the 30 dogs tested, which suggests and immune component may be involved in diabetes pathogenesis, at least in some dogs. The finding that only about 15% of dogs had autoantibodies is not too surprising, considering the study population was unselected with respect to diabetes etiology. It is important to remember that while canine diabetes is a clinically homogeneous disorder, it is likely a heterogeneous disease with respect to pathogenesis. Further, despite the impression given by textbooks and review articles, the prevalence of autoimmunity in the overall population of canine diabetics is not known. Many questions remain to be investigated regarding the role of autoimmunity in the genesis of canine diabetes. The current study provides a useful starting point from which to pursue these questions. (TS) Davison LJ, Weenink SM, Christie MR, et al. Autoantibodies in GAD65 and IA-2 in canine diabetes mellitus. Vet Immunol Immunopathol (2008), doi:10.1016/j.vetimm.2008.06.016 (electronic version prior to publication).