Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F. Issue 1 (28th June 2018)

• Record Type: Journal Article
• Authors: Santos, Margarida Rodrigues; Couto, Ana Rita; Foroni, Iris; Bettencourt, Bruno Filipe; Li, Zhixiu; Meneses, Raquel; Wheeler, Lawrie; Pereira, Joaquim; Pimentel-Santos, Fernando; Fonseca, João Eurico; Alves, Helena; Martinho, António; Lima, Manuela; Brown, Matthew A; Bruges-Armas, Jácome
• Is Part Of: RMD open. Volume 4:Issue 1(2018)
• Publication Date: 2018-06-28
• Subjects: spondyloarthritis -- ankylosing spondylitis -- autoimmune diseases -- inflammation -- gene polymorphism -- HLA.; Musculoskeletal system -- Diseases -- Periodicals; Rheumatism -- Periodicals; 616.7005
• DOI: 10.1136/rmdopen-2018-000677
• Languages: English
• ISSNs: 2056-5933

Abstract

Abstract : Objectives: Ankylosing spondylitis (AS) is the most prevalent form of spondyloarthritis, with a known genetic association with the HLA-B27 molecule. The aim of this study was to assess the contribution of the HLA-G, HLA-E and HLA-F to AS susceptibility/protection in Portuguese patients with HLA-B27 AS and HLA-B27 unaffected controls. Methods: High-resolution typing of HLA-G, HLA - E and HLA - F was performed in 228 patients with HLA-B27 AS and 244 HLA-B27 unaffected controls. Allelic, genotypic and haplotypic frequencies were compared between cohorts. To replicate the results, single nucleotide polymorphisms (SNPs) in HLA-E and HLA-F genes were typed in Australian cohorts. For further confirmation, a group of European-descent patients with AS and unaffected controls were genotyped for Major Histocompatibility Complex SNPs using the Illumina microarray. Results: In the Portuguese population, no significant differences were found in HLA-G . For HLA-E, a significant difference was detected for the genotype HLA-E*01:01:01/01:03:01 (p=0.009; pc=0.009; OR=0.51), with a protection effect. For HLA-F, significant differences were detected in the allele HLA-F*01:01:02 (p=0.0049; pc=0.0098; OR=0.60) and corresponding SNP rs2075682 (p=0.0004; pc=0.0008; OR=0.53), suggesting protection and in the genotype HLA-F*01:01:01/01:03:01 (p=0.011; pc=0.043; OR=2.00), suggesting a susceptibility effect. Three G-E-F haplotypes with significant differences were detected but occur in a very small number of individuals. The only significant differences detected in the replication studies were for HLA-E rs1059510 in the Australians and for HLA-F rs1736924 in the European-descent cohorts. Conclusion: Our results reveal suggestive AS protective and susceptibility effects from both HLA-E and HLA - F loci, however with population differences. To our knowledge, this is the first study showing association of HLA-F with AS.