Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Dermatomyositis (DM) is characterized by inflammation of the skin and skeletal muscle, and is occasionally complicated by interstitial lung disease or concomitant malignancy. It has been recognized that myositis-specific autoantibodies (MSAs) are correlated with unique sets of clinical manifestations. The mechanisms underlying production of MSAs still remain uncertain, but genetic factors, such as human leukocyte antigen (HLA) class II genes, are reported to play some roles. Anti-Jo-1 and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are associated with HLA-DRB1*04:05 in Japanese population, but there is no information on the HLA-DRB1 association with anti-transcriptional intermediary factor 1-γ (TIF1-γ) antibody.
Methods: We enrolled 36 DM patients with anti-TIF1-γ antibody, 24 DM patients without anti-TIF1-γ antibody, and 161 ethnicity-matched healthy controls, who were recruited form 7 medical centers across Japan. Eighteen patients with anti-TIF1-γ antibody had concomitant malignancy which was defined by the diagnosis within 2 years before or after DM diagnosis. HLA typing was performed by next-generation sequencing method. Strength of associations was estimated by odds ratios (OR) and 95% confidence intervals (CI) and frequencies were compared using the Fisher’s exact test. P values were corrected by multiplying the number of alleles detected in Japanese.
Results: Although there is no statistically significant difference in distribution of HLA-DRB1 alleles among 3 groups, we found a trend toward increased frequencies of DRB1*04:03 and DRB1*04:06 in DM patients with anti-TIF1-γ, in comparison with DM patients without anti-TIF1-γ or healthy controls (19% versus 4% or 7%, 19% versus 0% or 8%, respectively). Interestingly, DRB1*04:03 and DRB1*04:06 alleles are evolutionally close and commonly have unique amino acid sequence (LLEQRRAE at positions 67-74) in the third hypervariable region of the HLA-DRB1. The frequency of having either DRB1*04:03 or DRB1*04:06 in DM patients with anti-TIF1-γ was significantly higher than the frequency in DM patients without anti-TIF1-γ (39% versus 4%; OR = 14.6, 95%CI 1.8-121, corrected P = 0.04) and tended to be higher than the frequency in healthy controls (39% versus 16%; OR = 3.3, 95%CI 1.5-7.3, corrected P = 0.09). No significant difference was observed in the frequency of DRB1 alleles between anti-TIF1-γ-positive patients with and without concomitant malignancy.
Conclusion: In Japanese population, anti–TIF1-γ antibody is associated with rare HLA–DRB1*04:03/*04:06 alleles, which are distinct from the DRB1 allele associated with other MSAs, including anti-Jo-1 and anti-MDA5 antibodies.
To cite this abstract in AMA style:Yamaguchi Y, Kuwana M, Kanaoka M, Watanabe T, Okiyama N, Gono T, Kodera M, Kambara T, Hamaguchi Y, Seishima M, Takehara K, Fujimoto M, Aihara M. HLA-DRB1*04:03/*04:06 As the Genetic Susceptibility to Dermatomyositis Positive for Anti-Transcriptional Intermediary Factor 1-γ Antibody in Japanese Population [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/hla-drb104030406-as-the-genetic-susceptibility-to-dermatomyositis-positive-for-anti-transcriptional-intermediary-factor-1-%ce%b3-antibody-in-japanese-population/. Accessed September 23, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hla-drb104030406-as-the-genetic-susceptibility-to-dermatomyositis-positive-for-anti-transcriptional-intermediary-factor-1-%ce%b3-antibody-in-japanese-population/