Journal Article

Linkage of Type I Interferon Activity and TNF-Alpha Levels in Serum with Sarcoidosis Manifestations and Ancestry

Patterson, Karen C., Baughman, Robert P., Sweiss, Nadera J., Zhang, Wei, Franek, Beverly S., Moller, David R., Niewold, Timothy B., Kariuki, Silvia N., Nair, Vaisak, Girijala, Lakshmi R., Garcia, Joe G. N., Bennett, Peggy

2011

Overview

Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes. We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations. Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups. Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / African Americans / Aged / Aged, 80 and over / Arthritis / Autoimmune diseases / B cells / Biological response modifiers / Case-Control Studies / Correlation / Critical care / Cytokines / Demography / Development and progression / Disease control / Enzyme-linked immunosorbent assay / European Continental Ancestry Group / Female / Genealogy and Heraldry / Genomes / Heart diseases / Hepatitis / Humans / Inflammation / Interferon / Interferon Type I - blood / Journalistic ethics / Liver diseases / Logistic Models / Lung diseases / Lupus / Lymphocytes / Male / Medical records / Medical research / Medicine / Middle Aged / Multivariate Analysis / Nervous system diseases / Pathogenesis / Patients / Phenotype / Regression analysis / Regression models / Rheumatology / Sampling methods / Sarcoidosis / Sarcoidosis - blood / Sarcoidosis - classification / Serum levels / Tumor necrosis factor / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Young Adult / α-Interferon