Autoantibodies against Protective Molecules—C1q, C‐Reactive Protein, Serum Amyloid P, Mannose‐Binding Lectin, and Apolipoprotein A1

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of several autoantibodies. Among the multiple factors involved in SLE development, apoptotic defects and impaired clearance of cellular debris have gained considerable interest, as they contribute to autoantigen overload. Several molecules of the innate immunity, also participate in the removal of damaged and apoptotic cells. Among them are C1q, C-reactive protein (CRP), serum amyloid P protein (SAP), mannose-binding lectin (MBL), and apolipoprotein A1 (APO A1). To evaluate the prevalence of autoantibodies against CRP, SAP, MBL, APO A1, and C1q among SLE patients, and their relationship with disease activity, a total of 150 SLE patients were screened for the presence of elevated antibody titers against C1q, CRP, SAP, MBL, and APO A1, utilizing the enzyme-linked immunosorbent assay (ELISA) method. Disease activity was assessed using the ECLAM or SLEDAI scores. The study population comprised two groups of patients: 100 patients with quiescent disease (median ECLAM score 2) comprised the first group, and 50 patients with active disease (median SLEDAI score 16) comprised group 2. Elevated titers of anti-CRP antibodies were significantly elevated only in group 1 (10% versus 4% of controls). Antibodies against SAP were evaluated only among patients in group 1, and were found at a significant high prevalence (20%). Elevated titers of anti-MBL antibodies were significantly elevated only in group 1 (15% versus 3.6%); and antibodies directed against APO A1 were significantly elevated in 21% of group 1, and 50% of group 2 patients. Elevated titers of anti-C1q were evaluated only in group 2, and were found at a significant prevalence of 66%. Significant correlation with disease activity was found only for anti-APO A1 antibodies, and only in group 1. Several patients harbored more than one of the autoantibodies tested. In patients with SLE, autoantibodies directed against protective molecules, that is, acute-phase proteins involved in the disposal of cellular and nuclear debris, can be detected. These autoantibodies may play a pathogenic role in the development or perpetuation of autoimmunity in SLE.

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…During the last decade, many groups have reported the presence of autoantibodies directed against PRMs and acute phase proteins in different conditions [22][23][24][25][26]. We have demonstrated associations between anti-CRP antibody levels and disease activity, histopathology as well as response to therapy in lupus patients [27,28].…”

Annexin A2 and A5 Serve as New Ligands for C1q on Apoptotic Cells

“…It is therefore possible that there are other factors preventing interaction of C1q with apoptotic cells in SLE patients, such as autoantibodies to C1q ligands. Interestingly, autoantibodies to both annexin A2 and annexin A5 (21,22), as well as to other C1q ligands and C1q itself (43,44), have been found in patients suffering from autoimmune diseases such as SLE. These antibodies could either decrease direct binding of C1q to apoptotic cells or recruit additional C1q.…”

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…Since then, several groups have confirmed the finding of IgG class autoantibodies to CRP (anti-CRP) in SLE [12][13][14]. Analyses of antigen specificity of the anti-CRP assay used have clearly revealed that anti-CRP in SLE are directed against monomeric CRP, which is assumed to be the tissue-deposited form of the acute-phase reactant.…”