Tumour necrosis factor microsatellites in reactive arthritis

Tuokko, Juha; Koskinen, Sinikka; Westman, Pia; Yli-Kerttula, U; Toivanen, Auli; Ilonen, Jorma

doi:10.1093/rheumatology/37.11.1203

Cited by 31 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding is in agreement with our results [49]. Using microsatellites, an HLA B27-independent increase of a c1 allele was observed in ReA [87].…”

Section: The Strength and Human Leukocyte Antigen Relation Of Cellulasupporting

confidence: 94%

Cytokines and the immunopathology of the spondyloarthropathies

Braun

Sieper

1999

Curr Rheumatol Rep

View full text Add to dashboard Cite

In contrast to rheumatoid arthritis (RA), the triggering antigens are known in reactive arthritis (ReA) and Lyme arthritis. Thus, in these arthritides the antigen-specific T-cell response can be investigated in much detail and lessons possibly learned for other spondyloarthropathies (SpA) such as ankylosing spondylitis (AS) where T cells may well also play an important role in the pathogenesis. This article focusses on the immunopathology of the SpA, ReA, and AS with special reference to T cells and cytokines.

show abstract

“…This finding is in agreement with our results [49]. Using microsatellites, an HLA B27-independent increase of a c1 allele was observed in ReA [87].…”

Section: The Strength and Human Leukocyte Antigen Relation Of Cellulasupporting

confidence: 94%

Cytokines and the immunopathology of the spondyloarthropathies

Braun

Sieper

1999

Curr Rheumatol Rep

View full text Add to dashboard Cite

show abstract

“…The number of genetic polymorphisms around the TNFα gene locus is large24 and, in addition, there is a likelihood of linkage disequilibrium with HLA-DR. A study from Finland on TNF microsatellites in ReA showed that two alleles, TNFa6 and TNFc1, were increased in patients with ReA. Whereas the increase of TNFa6 was probably secondary to an association with HLA-B27, the increase of the TNFc1 allele seemed to be independent of HLA-B27 25. Of further interest, both the TNFa6 and the TNFc1 allele have been associated with low TNFα production in another study 26.…”

Section: Discussionmentioning

confidence: 94%

Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism

Rudwaleit

2001

Annals of the Rheumatic Diseases

158

View full text Add to dashboard Cite

Objective-To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon (IFN ), interleukin 4 (IL4), tumour necrosis factor (TNF ), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. Methods-Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFN , TNF , IL4, and IL10, and analysed by flow cytometry. TNF production was related to the genotype of the TNF promoter at the -308 and -238 polymorphisms. Results-In peripheral blood the percentage of TNF + T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNF + T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFN + T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNF + T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/ phenotype correlation (median 9.4% v 10.6%).

show abstract

“…However, these results remain controversial in the light of a third study that reported an association of the a11 allele with severe disease. 29 TNFa6 was also found to be associated with reactive arthritis in HLA-B27 positive subjects, 31 whereas patients with AS did not show any differences in TNFa allele distribution in comparison with HLA-B27 positive controls. 30 Increasing evidence shows that the pattern of cytokine secretion influences the course of spondyloarthropathies.…”

Section: Discussionmentioning

confidence: 95%

“…TNF microsatellites have been investigated in other rheumatic diseases like rheumatoid arthritis (RA), [27][28][29] AS, 30 and reactive arthritis. 31 Interestingly, two studies in RA reported an association of the TNFa6 allele with susceptibility 27 and severity 28 of RA. However, these results remain controversial in the light of a third study that reported an association of the a11 allele with severe disease.…”

Section: Discussionmentioning

confidence: 99%

Differential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasis

Hawranek

Grossmann²,

Stradmann‐Bellinghausen³

et al. 2002

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Objective: To investigate the potential association of tumour necrosis factor α (TNFα) microsatellite and promoter alleles with psoriatic arthritis (PsA). Methods: DNA from 89 white patients with PsA, 65 patients with psoriasis, and 99 healthy white controls was investigated for two TNFα promoter (-238 and -308) and three microsatellite polymorphisms (TNFa, c, and d). Patients had previously been studied by serology for HLA class I antigens and by sequence-specific polymerase chain reaction for DRB1* alleles. In addition, TNFα production of Ficoll separated peripheral blood mononuclear cells (PBMC) into culture supernatants after stimulation with lipopolysaccharide, αCD3 antibodies, phytohaemagglutinin, and streptococcal superantigen C was determined.Results: A significant, HLA class I independent increase of the TNFa6c1d3 haplotype was found in the group with PsA but not among patients with psoriasis (32% v 8%, pc<0.008; relative risk (RR)=5.3). In addition, patients with PsA showed a marked decrease of the TNF308A promoter allele (6% v 18%; pc<0.008; RR=3.5) compared with healthy controls, which was independent of the increased frequency of the -238A polymorphism in this group. PBMC from patients with PsA secreted significantly less TNFα than cells from patients without arthritis. In particular, the TNFa6 microsatellite was associated with decreased TNFα production. Conclusion: These data indicate that allelic variations at the TNFα locus influence susceptibility to PsA. Decreased production of TNFα is at least in part genetically determined and might be related to the development of arthritis. However, the association of the TNF308G allele with the disease also points to other disease related haplotypes with still unknown susceptibility genes.

show abstract

Tumour necrosis factor microsatellites in reactive arthritis

Cited by 31 publications

References 0 publications

Cytokines and the immunopathology of the spondyloarthropathies

Cytokines and the immunopathology of the spondyloarthropathies

Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism

Differential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasis

Contact Info

Product

Resources

About