Endothelial cell-binding activity of anti-U1-ribonucleoprotein antibodies in patients with connective tissue diseases

Abstract

SUMMARYIn order to elucidate the immunological properties of anti-U1-ribonucleoprotein (RNP) antibody, one of the autoantibodies detected in patients with connective tissue diseases (CTDs), we tested the endothelial cell-binding by anti-U1-RNP antibodies and epitopes on human pulmonary artery endothelial cells (HPAECs) to which the autoantibody bound. IgG fractions positive for anti-U1-RNP from patients with CTDs bound to the HPAECs. Furthermore, intact and F(ab H ) 2 IgG anti-U1-RNP purified by affinity chromatography also bound to endothelial cells. The binding activity of IgG fractions positive for anti-U1-RNP to the endothelial cells could be effectively absorbed by U1-RNP-Sepharose. An immunoblotting assay of purified IgG anti-U1-RNP antibodies showed that these antibodies could bind to various membrane proteins of NP40-treated HPAECs such as 68, 48, 43,38,33,29,28 and 24 kDa. Some bands, 68, 33, 28 and 24 kDa, seemed to correspond to components of U1-RNP, i.e. 68 kDa, A, B H and C peptides, respectively. We confirmed that the anti-U1-RNP antibody from patients with CTDs can directly recognize a variety of antigens on the endothelial surface of the pulmonary artery, including the components of U1-RNP or other unknown polypeptides. These results suggest that binding to pulmonary artery endothelial cells of this autoantibody may be one of the triggers of endothelial cell inflammation in CTDs.

Endothelial cell-binding antibodies in patients with systemic lupus erythematosus

“…4,12,20,21 In this study, a significant difference in the EC IgG levels was found between patients with active lupus nephritis and those without nephritis (see Fig. 4).…”

“…1 Antiendothelial cell antibodies (AECA) or endothelial cell-binding IgG antibodies (EC IgG) have been determined in various types of autoimmune diseases associated with vasculitis. [2][3][4] AECA or EC IgG have been detected in more than 50% of patients with SLE, and its correlation with disease activity has been reported. [5][6][7][8][9] However, the results of the relationship with clinical parameters such as levels of serum complement, antinuclear antibody (ANA), anti-DNA antibody (anti-DNA Ab), and antiphospholipid antibody (APA) differed in many reports.…”

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…In MCDT, anti-RNP antibodies have been found to interact with lung tissue in ways that could mediate MCTD lung pathology [183]. Immunization of susceptible mice with RNP antigen could induce MCTD-like serologic responses and some clinical manifestations [169].…”

A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen

“…Autoantibodies in MCTD recognize intact and apoptotically modified forms of individual U1 snRNP proteins (8,9), and frequently also recognize structures composed of multiple subunits of the U1 snRNP macromolecule (10). Moreover, anti-RNP antibodies have been found to interact with lung tissue in ways that could mediate MCTD lung pathology (11). In a small series of mice, we have previously found that direct immunization of a susceptible animal with RNP antigen could induce MCTD-like serologic responses and clinical manifestations (12).…”