Antibodies to type II collagen and HLA disease susceptibility markers in rheumatoid arthritis

Abstract

Objective. To seek associations between antibod-ies to native and denatured type II collagen (NCII and DCII) and HLA in rheumatoid arthritis (RA). Methods. One hundred fourteen patients with clinically well-defined RA were HLA-DR and DQ typed. Those who were DR4 positive were subtyped for DRB1*0401-*0408 alleles by polymerase chain reaction using allele-specific oligonucleotide probes. Antibodies to human NCII and DCII (heat-denatured) were measured by enzyme-linked immunosorbent assay. The frequency of HLA alleles was compared in patients grouped according to the presence and absence of antibodies to NCII and DCII. Results. Twenty-seven patients (24%) were positive for antibodies to NCII. There was a significant increase in the frequency of HLA-DR7 in anti-NCII-positive patients compared with anti-NCII-negative patients (30% versus 9%; P 0.019) and a significant decrease in HLA-DR3 (7% versus 28%; P 0.044). Repeating the analyses after excluding the 16 patients who were DR7 positive revealed a significant increase in the frequency of HLA-DR1 in anti-NCII-positive patients compared with anti-NCII-negative patients (63% versus 27%; P 0.045). Moreover, antibodies to NCII were associated with the third hypervariability region susceptibility sequence QRRAA that is present in DRB1*0101, *0404, *0405, and *0408 (84% versus 47%; P 0.0085); 24 of 27 anti-NCII-positive patients were positive for either DR7, DR1, or DRB1*0404 or *0408. Thirty patients (26%) were positive for antibodies to DCII. There was a significant increase in the frequency of HLA-DR3 in anti-DCII-positive patients compared with anti-DCII-negative patients (40% versus 18%; P 0.028). Conclusion. The genetic associations between HLA-DR alleles and antibodies to CII in RA patients is in keeping with the collagen-induced arthritis model and implicates autoimmunity to CII as a major component in the multifactorial pathogenesis of RA.

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

“…The genetic associations that have been reported between HLA-DR alleles and antibodies to type II collagen in RA patients implicate autoimmunity to type II collagen as a major component in the multifactorial pathogenesis of RA [71]. Thus, the findings in this report that IgG antibodies reacting with the proline-rich amino-terminal region of EBNA-2(N) are associated statistically significantly with SLE, primary SS, RA and secondary SS suggest that the molecular mimicry between the amino-terminal region of EBNA-2 and prolinerich cellular proteins, probably in combination with the epitope shift mechanism, may be related to pathogenesis in a subpopulation of patients with CTD.…”

HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) Use the Same Anchor Residues for Binding an Immunodominant Peptide Derived from Human Type II Collagen

“…[11][12][13][14]. In many of these cases, clinical evidence exists to support the presence of immunity to these Ags (15)(16)(17)(18)(19)(20)(21)(22), but it has been difficult to study this immunity at the molecular level in the context of the DR susceptibility alleles.…”

Consumption of hydrolyzable tannins-rich pomegranate extract suppresses inflammation and joint damage in rheumatoid arthritis

“…Joint histopathology in this animal model shows features that are remarkably similar to those seen in RA joints. The significance of the model also lies in the fact that CII is the major constituent protein of the cartilage in the diarthrodial joints-the primary site affected in RA (22,23). Because of many compelling similarities between CIA and RA, CIA is an excellent model to develop and test preventive and therapeutic approaches for the prevention and or treatment of arthritis in humans (24).…”