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  • Open Access

Low TNF-a and IFN-? in ankylosing spondylitis

  • 1
Arthritis Research & Therapy20013:68125

https://doi.org/10.1186/ar-2001-68125

  • Received: 23 March 2001
  • Accepted: 26 July 2001
  • Published:

Keywords

  • ankylosing spondylitis
  • cytokines
  • HLA-B27
  • TNF-a
  • IFN-?

Context

This study compares the prominence of Th1 and Th2 responses in ankylosing spondylitis (AS) patients with HLA -B27+ and -B27- controls. The influence of TNF-a promoter polymorphisms on T cell TNF-a production are also investigated.

Significant findings

The median percentage of CD4+ and CD8+ T cells producing TNF-a and IFN-? was lower in 25 AS patients (all B27+) than in 22 healthy B27- controls (P <0.01). This difference was also evident in 18 healthy B27+ controls compared with B27- controls (P <0.04). The percentages of IL-4-positive cells were similar in all groups. In the 18 B27- subjects, the TNF-a promoter genotype, defined by polymorphism at TNF-a-308, was not associated with different proportions of TNF-a- producing T cells. However, in 31 subjects (16 patients and 15 controls) from the B27+ group, individuals with the rare TNF-a-308 genotype 1/2 (n = 6) had higher percentages of TNF-a-producing T cells than individuals with the common genotype 1/1 (P <0.02) (n = 25). Indeed, the B27+ TNF-a-308 genotype 1/2 individuals had percentages of TNF-a-secreting T cells which were comparable with those in the B27-group.

The authors conclude that this suggests Th1 insufficiency in AS, rather than Th2 overactivity. A rare TNF-a promoter-308 allele (or another gene on that haplotype) modifies this phenotype in B27+ individuals and may be protective.

Comments

This is a well presented study which attempts to bridge the gap between association of B27 with AS and pathophysiology. The authors have explored the cytokine production of peripheral T cells in patients with AS (all B27+) and controls (B27+ and B27-) and have identified a 'Th1 deficiency' phenotype in patients and in B27+ controls. The AS and control groups each included ~20 individuals and appropriate statistical analyses were applied. The stimulation of T cells with PMA and ionomycin is unphysiological; however, the technique probably reveals a genuine difference in T cell function in this study. This 'Th1 deficiency' can apparently be rectified, in B27+ subjects, by the presence of a rare TNF-a haplotype. However, the number of individuals with the rare genotype is small and this effect should be regarded as intriguing but inconclusive at this stage. Ideally, the differences in T cell cytokine production should be confirmed following physiological challenges, such as infection with influenza or tetanus toxoid vaccination.

Methods

Stimulation of T cells with phorbol myristate acetate (PMA)/ionomycin, FACS analysis with intracellular staining, amplification-refractory mutation system PCR

Additional information

Authors’ Affiliations

(1)
Institute of Molecular Medicine, Oxford, UK

References

  1. Rudwaleit M, Siegert S, Yin Z, Eick J, Thiel A, Radbruch A, Sieper J, Braun J: Low T cell production of TNF-a and IFN-? in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism. Ann Rheum Dis. 2001, 60: 36-42.PubMedPubMed CentralView ArticleGoogle Scholar

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