Protective Molecules–C-Reactive Protein (CRP), Serum Amyloid P (SAP), Pentraxin3 (PTX3), Mannose-Binding Lectin (MBL), and Apolipoprotein A1 (Apo A1), and Their Autoantibodies: Prevalence and Clinical Significance in Autoimmunity

Abstract

Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity, as they can contribute to autoantigen overload, and may initiate an autoimmune response. The pentraxins are a group of highly conserved proteins including the short pentraxins, C-reactive protein (CRP) and serum amyloid-P (SAP), and the long pentraxin-3 (PTX3), which are all involved in innate immunity and in acute-phase responses. Mannan-binding lectin (MBL) is an activator of the complement system, and Apolipoprotein A-1 (Apo A-1) is pivotal in the cholesterol homeostasis and has anti-inflammatory properties. In addition to their role in innate immunity and inflammation, each of these five proteins participates in the removal of damaged and apoptotic cells. In this review, we discuss the clinical significance of different levels of these proteins, their role in the induction or protection from autoimmunity, and the presence of specific autoantibodies against them in the different autoimmune diseases.

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

“…On the other hand, plasma hs‐CRP levels strongly correlated with the levels of IL1‐RA. As anti‐inflammatory effects of CRP are partially mediated through induction of IL1‐RA,42 this suggests that low hs‐CRP levels are linked with defective anti‐inflammatory responses.…”

C-reactive protein reference percentiles among pre-adolescent children in Europe based on the IDEFICS study population

“…5 Moreover, slightly elevated CRP is an independent predictor of coronary events and stroke and has been associated with cardiovascular mortality and all-cause mortality in adults. 6 An association between elevated CRP and markers for cardiovascular risk was reported in children as well. [7][8][9][10] In addition, increased CRP has been associated with cancer 11,12 and has shown to be a prognostic marker in various malignancies in adults, [13][14][15] whereas data in children are scarce.…”

Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans

“…Furthermore, rats display considerable luminal shedding of senescent colonocytes, whereas in humans mucosal phagocytosis is the main route of colonocyte disposal [39]. Especially, the latter observation may be of high relevance if Mptx indeed has a role in recognition, binding and clearance of apoptotic (dead) cells, similar to SAP and CRP [9,11,15,17,20]. The question is how this difference between man and rodents will affect extrapolation of dietary exposure and other studies in these animals.…”

“…Although we could not confirm this using immunochemistry due to high unspecific background signals of our antibodies (data not shown), we speculate that Mptx non-covalently attaches to the surface of intestinal epithelial cells, based on its potential calcium-mediated cell surface binding properties. There, similar to SAP and CRP [17,20], it may be involved in binding and clearance of dying cells. Possibly, Mptx binds specifically to apoptotic epithelial cells, similar to SAP [10], and mediates their clearance as part of the normal cell turnover processes in healthy colonic mucosa.…”

“…Reduced levels lead to autoimmune disease [2,26,29,30]. More specifically, they are thought to be involved in the recognition, binding and clearance of dead and apoptotic cells or cellular debris of pathogenic cells and host cells [9,11,15,17,20].…”