Rheumatoid Arthritis: Buckner JH

Buckner JH, Nepom GT. · Benaroya Research Institute, Virginia Mason Research Center, Seattle, Washington 98101, USA. · Curr Opin Rheumatol. · Pubmed #11981323 No free full text.

Abstract: Human leukocyte antigen genes associated with rheumatoid arthritis are commonly found in the unaffected population, implying that causal mechanisms of disease involve interactions between these genes and other factors. A variety of approaches-genetic, structural, and immunologic-are used to explore possible molecular interactions that may contribute to understanding the basis for this disease association. The specific relation between human leukocyte antigen-DR4 alleles and rheumatoid arthritis remains one of the strongest and most thoroughly studied examples of human leukocyte antigen risk genes among human autoimmune disorders.

Feser M, Derber LA, Deane KD, Lezotte DC, Weisman MH, Buckner JH, Mikuls T, O'Dell J, Gregersen PK, Holers VM, Norris JM. · Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado, USA. · J Rheumatol. · Pubmed #19286844 No free full text.

Abstract: OBJECTIVE: To evaluate the association between rheumatoid arthritis (RA)-related autoantibodies and plasma 25,OH vitamin D in subjects at risk for RA. METHODS: In 1210 subjects without RA, 76 were positive for anti-cyclic citrullinated peptide antibodies or for at least 2 rheumatoid factors (RF; by nephelometry: RF-IgM, RF-IgG, RF-IgA). 25,OH vitamin D was measured in these cases and 154 autoantibody-negative controls from this cohort. RESULTS: 25,OH vitamin D levels did not differ between cases and controls (adjusted OR 1.23, 95% CI 0.93-1.63). CONCLUSION: Vitamin D concentrations are not associated with RA-related autoimmunity in unaffected subjects at increased risk for RA.

Gebe JA, Novak EJ, Kwok WW, Farr AG, Nepom GT, Buckner JH. · Benaroya Research Institute, Virginia Mason Research Center, Seattle, WA 98101, USA. · J Immunol. · Pubmed #11544312 links to  free full text

Abstract: Plasticity of TCR interactions during CD4(+) T cell activation by an MHC-peptide complex accommodates variation in the peptide or MHC contact sites in which recognition of an altered ligand by the T cell can modify the T cell response. To explore the contribution of this form of TCR cross-recognition in the context of T cell selection on disease-associated HLA molecules, we have analyzed the relationship between TCR recognition of the DRB1*0401- and DRB1*0404-encoded HLA class II molecules associated with rheumatoid arthritis. Thymic reaggregation cultures demonstrated that CD4(+) T cells selected on either DRB1*0401 or DRB1*0404 could be subsequently activated by the other MHC molecule. Using HLA tetramer technology we identify hemagglutinin residue 307-319-specific T cells restricted by DRB1*0401, but activated by hemagglutinin residues 307-319, in the context of DRB1*0404. One such clone exhibits an altered cytokine profile upon activation with the alternative MHC ligand. This altered phenotype persists when both class II molecules are present. These findings directly demonstrate that T cells selected on an MHC class II molecule carry the potential for activation on altered self ligands when encountering Ags presented on a related class II molecule. In individuals heterozygous for these alleles the possibility of TCR cross-recognition could lead to an aberrant immune response.