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Arthritis Rheum. 2008 Sep;58(9):2818-23. doi: 10.1002/art.23728.

The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-alpha activity and low tumor necrosis factor alpha levels in patients with lupus.

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  • 1University of Chicago, Chicago, Illinois 60637, USA.

Abstract

OBJECTIVE:

The C1858T polymorphism in PTPN22 has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon-alpha (IFNalpha) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the PTPN22 risk variant may shift serum cytokine profiles to higher IFNalpha activity, resulting in risk of disease.

METHODS:

IFNalpha was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor alpha (TNFalpha) was measured by enzyme-linked immunosorbent assay. The rs2476601 single-nucleotide polymorphism in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFNalpha predominant, IFNalpha and TNFalpha correlated, TNFalpha predominant, and both IFNalpha and TNFalpha low).

RESULTS:

SLE patients carrying the risk allele of PTPN22 had higher serum IFNalpha activity than patients lacking the risk allele (P = 0.027). TNFalpha levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFNalpha-predominant and IFNalpha and TNFalpha-correlated groups as compared with patients in the TNFalpha-predominant and both IFNalpha and TNFalpha-low groups (P = 0.001). Twenty-five percent of male patients carried the risk allele, compared with 10% of female patients (P = 0.024); however, cytokine skewing was similar in both sexes.

CONCLUSION:

The autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFNalpha activity and lower TNFalpha levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele.

PMID:
18759295
[PubMed - indexed for MEDLINE]
PMCID:
PMC2621106
Free PMC Article
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