Epitope specificity and significance in systemic autoimmune diseases

Abstract

Autoimmune diseases are characterized by self-reactive immune processes mediated by B and T cells. These disorders exhibit a spectrum of clinical features that range from local or organ specific to systemic diseases. Although a variety of putative mechanisms that trigger the loss of tolerance and thus the genesis of autoimmunity have been identified, for the most part the precise mechanisms remain elusive. Nevertheless, it is widely appreciated that autoantibodies are useful both in the diagnosis of autoimmune disorders and as molecular biological tools to study cellular processes in which the target antigens are involved. Several methods and technologies, including protein fragments, synthetic peptides, phage display, or structural analyses have been developed for the characterization of the specificity of the autoimmune reactions. The present review provides an overview of the autoantibody epitopes in systemic autoimmune diseases as they relate to the clinical relevance and applications of certain autoepitopes and the technologies that are used to classify and identify them.

MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4

“…In AChR MG and other autoimmune diseases, autoantibodies often require a discontinuous stretch of amino acids that comprise a structural epitope (28)(29)(30)(31)(32). To determine whether the autoantibodies to MuSK recognize a linear epitope in the first Ig-like domain of MuSK, we used a competition ELISA with overlapping 20-mer peptides from the first Ig-like domain ( Fig.…”

Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

“…Sm autoantigens comprise a ring of 7 small nuclear ribonucleoprotein (snRNP) common core proteins (B, D1, D2, D3, E, F & G) with the snRNA passing through ring [8]. While SmB and SmD are the major targets of anti-Sm humoral autoimmunity, anti-SmD is considered to have the highest specificity for SLE [9]. Immune complexes of anti-Sm and snRNP particles are thought to perpetuate systemic autoimmunity by inducing type I interferon in plasmacytoid dendritic cells via combined Fc receptor and TOLL-like receptor 7 engagement [10,11].…”

The Association of Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibodies in Patients With Rheumatoid Arthritis and Interstitial Lung Disease

“…In another study, anti-Jo-1 antibodies have also been reported in 15-30% of PM patients and 60-70% of ILD patients. 17 Other anti-ARS antibodies are less predominant in inflammatory myopathies. In our study, however, anti-Jo-1 antibody was detected in only one RA patient, whereas anti-PL-7 antibody was detected in six patients (42.9% of all anti-ARS antibody-positive patients).…”