Michael T Aubrey

Publications (2)11.91 Total impact

• Article: Association of the HLA-DRB1 epitope LA(67, 74) with rheumatoid arthritis and citrullinated vimentin binding.

  Brian M Freed, Ronald P Schuyler, Michael T Aubrey
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  ABSTRACT: Although rheumatoid arthritis (RA) has long been associated with an HLA-DRB1 shared epitope, a systematic search for other epitopes has never been conducted. In addition, the relationship between these epitopes and the binding of citrullinated autoantigens has not been investigated. We developed a program that can analyze HLA data for all possible epitopes of up to 5 amino acids and used this program to assess the shared epitope hypothesis in RA. We analyzed high-resolution data from the International Histocompatibility Working Group, which included a group of 488 patients with RA and a group of 448 racially and ethnically balanced control subjects, for all combinations of up to 5 amino acids among polymorphic HLA-DRB1 positions 8-93. Statistical significance was determined by chi-square and Fisher's exact tests, with a false discovery rate correction. Three residues (V(11), H(13), and L(67)) were found to have the highest degree of association with RA susceptibility (P < 10(-11)), and D(70) was found to correlate best with RA resistance (P = 2 × 10(-11)). Of >2 million epitopes examined, LA(67, 74) exhibited the highest correlation with RA susceptibility (P = 2 × 10(-20); odds ratio 4.07 [95% confidence interval 3.07-5.39]). HLA alleles containing the LA(67, 74) epitope exhibited significantly greater binding to citrullinated vimentin(65-77) than did alleles containing D(70). Only 1 allele (DRB1*16:02) contained both LA(67, 74) and D(70); it bound citrullinated vimentin weakly and was not associated with RA. The findings of these studies confirm the importance of HLA-DRB1 amino acids in pocket 4 for the binding of citrullinated autoantigens and susceptibility to RA.
  Arthritis & Rheumatism 08/2011; 63(12):3733-9. · 7.87 Impact Factor
• Article: Peanut-allergic subjects and their peanut-tolerant siblings have large differences in peanut-specific IgG that are independent of HLA class II.

  Stephen C Dreskin, Mark T Tripputi, Michael T Aubrey, S Shahzad Mustafa, Dan Atkins, Harvey L Leo, Benjamin Song, Darcy Schlichting, Hanna Talwar, Qian Wang, Brian M Freed
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  ABSTRACT: We enrolled 53 peanut-allergic subjects and 64 peanut-tolerant full siblings, measured peanut-specific IgG and IgE, determined HLA class II at high resolution, and analyzed DRB1 alleles by supertypes. Peanut-specific IgG and IgE were elevated in the peanut-allergic subjects (p<0.0001) but did not stratify with HLA alleles, haplotypes, or supertypes. There were no significant differences in HLA class II between the peanut-allergic and peanut-tolerant siblings but there was an increased frequency of DRB1*0803 in both sets of siblings compared to unrelated controls (p(c)=4.5×10⁻⁹). Furthermore, we identified 14 sibling pairs in which the peanut-allergic and the peanut-tolerant siblings have identical HLA class II and again found an elevation of anti-peanut IgG in the peanut-allergic subjects (p<0.0001). In conclusion, although DRB1*0803 may identify a subset of families with increased risk of peanut allergy, differences in peanut-specific immunoglobulin production between peanut-allergic subjects and their peanut-tolerant siblings are independent of HLA class II.
  Clinical Immunology 12/2010; 137(3):366-73. · 4.05 Impact Factor