HLA association with the susceptibility to anti-synthetase syndrome
Sara Remuzgo‐Martínez, Belén Atienza‐Mateo, J. Gonzalo Ocejo‐Vinyals, Verónica Pulito‐Cueto, D. Prieto-Peña, Fernanda Genre, Ana Márquez, Javier Llorca, Víctor Manuel Mora Cuesta, David Iturbe‐Fernández, Laura Rodrigáñez, Norberto Ortego‐Centeno, Nair Pérez Gómez, Antonio Mera, Julia Martínez‐Barrio, Francisco Javier López‐Longo, Leticia Lera‐Gómez, C. Moriano, Elvira Díez, Eva Tomero, Jaime Calvo‐Alén, Fredeswinda Romero-Bueno, Olga Sánchez‐Pernaute, Laura Nuño, Gema Bonilla, Ignacio Grafiá, Sergio Prieto‐González, Javier Narváez, Ernesto Trallero‐Araguás, Albert Selva-O’Callaghan, Oreste Gualillo, Javier Martı́n, Lorenzo Cavagna, Santos Castañeda, José M. Cifrián, Elisabetta Renzoni, Raquel López‐Mejías, Miguel Á. González‐Gay
Abstract
OBJECTIVE: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). METHODS: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. RESULTS: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. CONCLUSIONS: Our results support the association of the HLA complex with the susceptibility to ASSD.