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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 267430, 6 pages
http://dx.doi.org/10.1155/2013/267430
Research Article

Familial Aggregation of High Tumor Necrosis Factor Alpha Levels in Systemic Lupus Erythematosus

1Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA
2Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
3Division of Rheumatology and The Center for Autoimmune Genomics & Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
4US Department of Veterans Affairs Medical Center, Cincinnati, OH 45229, USA
5Division of Rheumatology and Department of Immunology, Mayo Clinic, 200 1st Street SW, Guggenheim building 3-42, Rochester, MN 55905, USA

Received 17 July 2013; Accepted 19 August 2013

Academic Editor: George N. Goulielmos

Copyright © 2013 Dorothy Mangale et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Systemic lupus erythematosus (SLE) patients frequently have high circulating tumor necrosis factor alpha (TNF-α) levels. We explored circulating TNF-α levels in SLE families to determine whether high levels of TNF-α were clustered in a heritable pattern. We measured TNF-α in 242 SLE patients, 361 unaffected family members, 23 unaffected spouses of SLE patients, and 62 unrelated healthy controls. Familial correlations and relative recurrence risk rates for the high TNF-α trait were assessed. SLE-affected individuals had the highest TNF-α levels, and TNF-α was significantly higher in unaffected first degree relatives than healthy unrelated subjects . No Mendelian patterns were observed, but 28.4% of unaffected first degree relatives of SLE patients had high TNF-α levels, resulting in a first degree relative recurrence risk of 4.48 . Interestingly, the median TNF-α value in spouses was similar to that of the first degree relatives. Concordance of the TNF-α trait (high versus low) in SLE patients and their spouses was strikingly high at 78.2%. These data support a role for TNF-α in SLE pathogenesis, and TNF-α levels may relate with heritable factors. The high degree of concordance in SLE patients and their spouses suggests that environmental factors may also play a role in the observed familial aggregation.