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. 2018 Jun 28;4(1):e000677.
doi: 10.1136/rmdopen-2018-000677. eCollection 2018.

Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F

Margarida Rodrigues Santos  1 , Ana Rita Couto  1 , Iris Foroni  1 , Bruno Filipe Bettencourt  1 , Zhixiu Li  2 , Raquel Meneses  1 , Lawrie Wheeler  2 , Joaquim Pereira  1 , Fernando Pimentel-Santos  3 , João Eurico Fonseca  4 , Helena Alves  5 , António Martinho  6 , Manuela Lima  7 , Matthew A Brown  2 , Jácome Bruges-Armas  1   3
Affiliations

Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F

Margarida Rodrigues Santos et al. RMD Open. .

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.

Keywords: HLA; ankylosing spondylitis; autoimmune diseases; gene polymorphism; inflammation; spondyloarthritis.

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Conflict of interest statement

Competing interests: None declared.

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