Anti-Pentraxin Antibodies in Autoimmune Diseases: Bystanders or Pathophysiological Actors?

Abstract

Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.

Keywords: ANCA-associated vasculitis; anti-pentraxin autoantibodies; autoimmunity; pentraxins; systemic lupus erythematosus.

Figure 1

Anti-pentraxin antibodies in autoimmunity: a hypothetical model. Anti-pentraxin antibodies are found elevated at autoimmune disease onset and decline during remission phases, suggesting that they are, at least, diagnostic markers, playing a “bystander role” (left panel). Based on the role of pentraxins in efferocytosis, two hypotheses can be drawn about a hypothetical “pathological role” of anti-pentraxin Abs (right panel). In a physiological context, apoptotic cells are opsonized by pentraxins (PTX) that facilitate their engulfment. This process promotes tolerogenic phagocytes and prevents inflammation. The presence of anti-pentraxin Abs can lead to the initiation of adaptive immune responses against dying cell antigens and NETosis, a pro-inflammatory process associated with the release of autoantigens. First, anti-PTX Ab may behave as neutralizing antibodies, inhibiting apoptotic cells engulfment by professional antigen-presenting cells, leading to the evolution of dying cells from early to late apoptotic/necrotic cells. These dying cells release potent inflammatory DAMPs inducing the activation of antigen-presenting cells. Second, anti-PTX Ab can be considered as activating Ab, inducing the phagocytosis of dying cells via FcγR. This process also induces the activation of antigen-presenting cells, favoring the initiation of MHC-I and MHC-II immune responses through antigen presentation and cross-presentation. Whatever the “function” of anti-pentraxin Ab, they initiate an inflammatory process leading to a deleterious amplification loop responsible for tissue damages.