Ankylosing spondylitis (AS) is a common chronic rheumatic disease whose aetiology arises as a result of the contribution of environmental factors and a strong genetic component.¹ One crucial point in the pathogenesis of the disease is the regulation of T cell response.² Recently, it has been shown that the functional 1858 C/T polymorphism of PTPN22, the gene that encodes a lymphoid-specific protein tyrosine phosphatase (LYP), is associated with several autoimmune diseases (ADs), supporting the hypothesis that common aetiopathological pathways are shared by different ADs.³ LYP has a key role as a negative regulator of T cell activation.⁴ It seems that the single nucleotide polymorphism (SNP) 1858 C/T disrupts the interaction between LYP and Csk, probably leading to an overactivated T cell response.⁵

Taking into account the functional relevance of the PTPN22 1858 C/T polymorphism, and its association with a wide range of ADs, this study aimed at investigating for the first time the possible implication of the SNP for susceptibility to AS.

A total of 197 patients with AS meeting the modified New York criteria for AS⁶ were recruited from Hospital Virgen de las Nieves (Granada, Spain) and Hospital Xeral-Calde (Lugo, Spain). A total of 551 blood bank donors and bone marrow donors were included as healthy controls. All the subjects were of white Spanish origin. Samples were genotyped for PTPN22 1858C→T variants as previously described.⁷ Statistical analysis to compare allelic and genotypic distributions was performed by χ² test using Statcalc program (Epi Info 2002; Centers for Disease Control and Prevention, Atlanta, GA, USA).

We found no statistically significant differences after comparing allele and genotypic frequencies of PTPN22 1858C→T between patients with AS and controls (table 1).

In addition, comparison of genotypes carrying the T allele (CT+TT v CC) between patients with AS and controls did not reach statistically significant skewing.

Similarly, no statistically significant differences were found when we stratified patients with AS according to HLA-B27 status (data not shown).

The lack of association that we show here might be due to a false negative, given our underpowered sample size. Because of this, we cannot completely exclude a weak effect of this polymorphism in AS and further investigations in different populations are required.

Recent studies of the PTPN22 1858C/T polymorphism have reported a lack of association with some ADs.⁸ The lack of association with these ADs may indicate a common aetiological mechanism that is different from the associated ADs. It has been proposed that the susceptibility of the polymorphism may predispose individual subjects to autoimmunity by promoting the generation of autoantibodies that contribute to disease onset and progression.⁹ The existence of humoral abnormalities in PTPN22 knockout mice strengthens the hypothesis that autoantibody production is a prominent feature of the ADs that are associated with PTPN22.¹⁰ Based on that, the lack of autoantibody production in AS might explain the negative association between PTPN22 1858C/T polymorphism and this condition.

In conclusion, the lack of association of PTPN22 with some ADs emphasises that susceptibility factors for AD are not shared among all ADs.