Sera from Children with Type 1 Diabetes mellitus React against a New Group of Antigens Composed of Lysophospholipids

Abstract

Several autoantibodies related to Type 1 diabetes mellitus and their corresponding autoantigens have been previously identified. While peptide antigens are more widely recognized, lipid antigens like sulfatides and gangliosides are also known epitopes for the diabetic humoral immune response. Islet cell antibodies (ICA) in Type 1 diabetes are heterogeneous immunoglobulins directed against selected antigens in the islets of Langerhans. Moreover, ICA may be the best predictive marker of disease in family members of patients with Type 1 diabetes. The aims of this study were: (1) to purify lipids from porcine pancreas that contain ICA epitopes; (2) to characterize these lipid antigens, and (3) to use the purified lipids in an assay to detect antibodies in patients with Type 1 diabetes. A unique family of 4 lysophospholipids, 1 fully characterized as lysophosphatidylmyoinositol, partially inhibited ICA staining, and therefore, were considered to be candidate antigens for an ICA immunoassay. Using a dot blot immunoassay, we detected antibodies directed against these phospholipids in 28 out of 46 (61%) diabetic sera, while detecting only 1 false positive out of 28 nondiabetic sera (3.6%; p < 0.0001 comparing diabetic vs. nondiabetic serum). Therefore, lysophospholipid immunoassay positivity is present in sera of Type 1 diabetic patients. Furthermore, we detected 15 out of 23 ICA-negative diabetic sera (65.2%), showing that our phospholipid immunoassay does not correlate with ICA positivity.

Group 1B Phospholipase A2–Mediated Lysophospholipid Absorption Directly Contributes to Postprandial Hyperglycemia

“…The results of this study further document that the Pla2g1b-digested product LPC is directly responsible for suppression of hepatic glucose metabolism. In view of studies showing increased LPC levels in patients with type 2 diabetes (27,28), the current study suggests that inhibition of Pla2g1b may be a viable strategy to prevent the onset of type 2 diabetes in individuals consuming a high-glucose/high-fat diet.…”

Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset

“…Alterations in phospholipids, especially lysophospholipids, and cholesterol esters have previously been described in T1DM with well controlled diabetes compared with healthy controls, ,,, with Fievet and colleagues explaining this as arising from lipoprotein remodelling and an increased pro-inflammatory state for those with T1DM. Indeed, in children, autoantibodies to a number of lysophospholipids have also been described, demonstrating the interplay between this class of lipid and autoimmune disease.…”

Type 1 diabetes mellitus prevention

“…Most autoantibodies associated with T1DM recognise peptide antigens, but antibodies against lipid antigens (p/gangliosides and sulfatides) have also been described [ 15 , 16 ].…”