PMID- 19877033 OWN - NLM STAT- MEDLINE DCOM- 20100104 LR - 20220409 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 60 IP - 11 DP - 2009 Nov TI - Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. PG - 3436-46 LID - 10.1002/art.24936 [doi] AB - OBJECTIVE: Up-regulation of whole blood type I interferon (IFN)-driven transcripts and chemokines has been described in a number of autoimmune diseases. An IFN gene expression "signature" is a candidate biomarker in patients with dermatomyositis (DM). This study was performed to evaluate the capacity of IFN-dependent peripheral blood gene and chemokine signatures and levels of proinflammatory cytokines to serve as biomarkers for disease activity in adult and juvenile DM. METHODS: Peripheral blood samples and clinical data were obtained from 56 patients with adult or juvenile DM. The type I IFN gene signature in the whole blood of patients with DM was defined by determining the expression levels of 3 IFN-regulated genes (IFIT1, G1P2, and IRF7) using quantitative real-time reverse transcription-polymerase chain reaction. Multiplexed immunoassays were used to quantify the serum levels of 4 type I IFN-regulated chemokines (IFN-inducible T cell alpha chemoattractant, IFNgamma-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], and MCP-2) and the serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6). RESULTS: DM disease activity correlated significantly with the type I IFN gene signature (r = 0.41, P = 0.007) and with the type I IFN chemokine signature (r = 0.61, P < 0.0001). Furthermore, the serum levels of IL-6 were significantly correlated with disease activity (r = 0.45, P = 0.001). In addition, correlations between the serum levels of IL-6 and both the type I IFN gene signature (r = 0.47, P < 0.01) and the type I IFN chemokine signature (r = 0.71, P < 0.0001) were detected in patients with DM. CONCLUSION: These results suggest that serum IL-6 production and the type I IFN gene signature are candidate biomarkers for disease activity in adult and juvenile DM. Coregulation of the expression of IFN-driven chemokines and IL-6 suggests a novel pathogenic linkage in DM. FAU - Bilgic, Hatice AU - Bilgic H AD - University of Minnesota, Minneapolis, MN 55455, USA. FAU - Ytterberg, Steven R AU - Ytterberg SR FAU - Amin, Shreyasee AU - Amin S FAU - McNallan, Kelly T AU - McNallan KT FAU - Wilson, Joseph C AU - Wilson JC FAU - Koeuth, Thearith AU - Koeuth T FAU - Ellingson, Sonja AU - Ellingson S FAU - Newman, Brant AU - Newman B FAU - Bauer, Jason W AU - Bauer JW FAU - Peterson, Erik J AU - Peterson EJ FAU - Baechler, Emily C AU - Baechler EC FAU - Reed, Ann M AU - Reed AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CCL8 protein, human) RN - 0 (CXCL10 protein, human) RN - 0 (CXCL11 protein, human) RN - 0 (Carrier Proteins) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL8) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL11) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (IFIT1 protein, human) RN - 0 (IRF7 protein, human) RN - 0 (Interferon Regulatory Factor-7) RN - 0 (Interferon Type I) RN - 0 (Interleukin-6) RN - 0 (RNA-Binding Proteins) RN - 0 (Ubiquitins) RN - 60267-61-0 (ISG15 protein, human) SB - IM CIN - Arthritis Rheum. 2010 Jul;62(7):2181-2; author reply 2182. PMID: 20506372 MH - Adaptor Proteins, Signal Transducing MH - Adolescent MH - Adult MH - Aged MH - Biomarkers/blood MH - Carrier Proteins/blood MH - Case-Control Studies MH - Chemokine CCL2/blood MH - Chemokine CCL8/blood MH - Chemokine CXCL10/blood MH - Chemokine CXCL11/blood MH - Chemokines/*blood MH - Child MH - Cytokines/blood MH - Dermatomyositis/*blood/diagnosis MH - Female MH - Humans MH - Interferon Regulatory Factor-7/blood MH - Interferon Type I/*genetics MH - Interleukin-6/*blood MH - Male MH - Middle Aged MH - RNA-Binding Proteins MH - *Severity of Illness Index MH - Ubiquitins/blood MH - Young Adult EDAT- 2009/10/31 06:00 MHDA- 2010/01/05 06:00 CRDT- 2009/10/31 06:00 PHST- 2009/10/31 06:00 [entrez] PHST- 2009/10/31 06:00 [pubmed] PHST- 2010/01/05 06:00 [medline] AID - 10.1002/art.24936 [doi] PST - ppublish SO - Arthritis Rheum. 2009 Nov;60(11):3436-46. doi: 10.1002/art.24936.