Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection. Comparison of antibody reactivity to commercial assays found that the citrullinated peptide was as effective in detecting ACPA as highly sensitive and specific commercial assays. The data presented demonstrate that the citrullinated EBNA-2 peptide indeed is recognised specifically by RA sera and that the single peptide is able to compete with assays containing multiple peptides. Furthermore, it could be hypothesized that RA may be caused by (a) specific strain(s) of EBV.

Role of Infections in the Pathogenesis of Rheumatoid Arthritis: Focus on Mycobacteria

“…Immune responses against microbes, such as Porphyromonas gingivalis [ 148 , 149 , 150 ], EBV [ 151 , 152 , 153 , 154 , 155 , 156 ], Human T-Lymphotropic Virus (HTLV) [ 157 ], Mycoplasma [ 158 , 159 ], Parvovirus B19 [ 160 ], Papilloma Virus [ 161 ], and Endogenous retroviruses (HERV) [ 162 ], have been reported in RA patients. On the other hand, some animal models of arthritis were developed, exploiting the infection of some pathogens, such as P. gingivalis [ 163 , 164 , 165 , 166 ], Mycoplasma [ 167 ], and EBV [ 168 , 169 ] [ Table 1 ].…”

Peptides, Antibodies, Peptide Antibodies and More

“…Synthetic peptides have numerous applications in research, diagnostics, and treatment [30,31], epitope characterization [31][32][33][34], production of peptide Abs [35], and vaccine development [36] (Table 1). Synthetic peptides are important therapeutics, and, in the last two decades, a significant renaissance in peptide drug discovery has occurred [37,38].…”

“…They successfully used a peptide representing a predicted immune-dominant (linear) epitope in Dengue Virus Envelope protein to detect Abs in infected individuals. Another particularly illustrative example of the use of peptides in diagnostics is the highly sensitive and specific detection of anti-citrullinated protein Abs, associated with rheumatoid arthritis, using synthetic peptides containing citrulline, which in vivo arises by post-translational modification (PTM) of Arg [31]. This also illustrates that peptides continue to be important reference compounds, especially with regard to PTMs.…”

EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls

“…Less hydrophobic plates (e.g., Polysorp) have lower binding capacity but in general give fewer problems with non-specific binding. In previous studies, Maxisorp plates were primarily used without standards, yielding only absorbances as a measure of antibody reactivity [28,29]. Here, we used Polysorp plates in combination with a standard to determine relative concentrations of IgM, IgA and IgG to EBNA1 and EAD.…”