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

Silvia N. Kariuki, Mary K. Crow, Timothy B. Niewold

Research output: Contribution to journalArticle

68 Scopus citations

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-α (IFNα) 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 IFNα activity, resulting in risk of disease. Methods. IFNα was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor α (TNFα) 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 (IFNα predominant, IFNα and TNFα correlated, TNFα predominant, and both IFNα and TNFα low). Results. SLE patients carrying the risk allele of PTPN22 had higher serum IFNα activity than patients lacking the risk allele (P = 0.027). TNFα levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFNα-predominant and IFNα and TNFα-correlated groups as compared with patients in the TNFα-predominant and both IFNα and TNFα-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 IFNα activity and lower TNFα levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele.

Original languageEnglish (US)
Pages (from-to)2818-2823
Number of pages6
JournalArthritis and rheumatism
Volume58
Issue number9
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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