Identification and characterization of adipose tissue-derived human antibodies with “anti-self” specificity

Abstract

Abstract We have previously shown that the human obese adipose tissue (AT) contributes to increased secretion of adipocyte-specific IgG antibodies in individuals with obesity. We have also shown that this occurs without any exogenous stimulation, because the ongoing process of cell death in the obese AT leads to the release of “self” antigens able to induce chronic stimulation of B cells. Here, we confirm and extend our initial observation on a different cohort of individuals, and we show that also the plasma of obese individuals is enriched in IgG antibodies with specificities for adipocyte-derived antigens. Adipocyte-specific IgG secreted in the obese AT are significantly correlated with those present in plasma. Using immunoprecipitation and mass spectrometry, we have identified these antigenic specificities. The antigens are almost exclusively intracellular or cell-associated, usually not “self” antigens, but they are released by cells dying in the AT. These antigens will be used in protein arrays to screen plasma from individuals with obesity and also with autoimmune diseases. We have indeed preliminary evidence that the plasma of Rheumatoid Arthritis patients is enriched in adipocyte-specific IgG antibodies, suggesting that obesity may contribute to pathogenicity in autoimmune patients. Finally, we show for the first time that not only macrophages but also adipocytes in the obese AT are efficient antigen-presenting cells and stimulate the secretion of IgG autoimmune antibodies. They do so because they express the antigen-presenting molecules CD1d and, to a lesser extent, MHC class II, as well as the co-stimulatory molecule CD86. These results may lead to the development of novel therapeutic strategies to controlautoimmunity.