Autoimmune rheumatologic diseases
Mitochondrial DNA (mtDNA), released upon tissue damage is a danger signal and a potent inflammatory trigger. The abundance of mtDNA is correlated with aging, frailty, cardiovascular diseases, diabetes, SIRS, and suggested as a cancer biomarker. We proposed to study its levels by quantitative real-time PCR in plasma from 19 rheumatoid arthritis (RA) patients before and at least 12 months after starting biological therapy (11 anti-TNFα, 5 CTLA-Ig and 3 anti-IL6R); clinical status was assessed by DAS28, ESR and CRP, and concentration of 40 cytokines was measured by Quantibody Human Inflammatory Array 3 (RayBiotech,Inc. Norcross, GA). Plasma mtDNA was lower (p < 0.05) in RA patients before biologicals compared with 20 age-matched healthy controls (mean 63 and 62 yrs) but it increased after therapy by 1log10on average (p < 0.01). We found no correlation between mtDNA levels and disease activity at baseline and follow-up; changes observed were unrelated to plasma values of cytokines studied, including TNFα and IL6 or IL6R. 33/40 cytokines decreased after biological therapy, with five (including TNFα and TNFRII) showing a significant reduction (p < 0.001). The others were MCP-1/CCL2, IL7 and PDGF-BB, produced by stromal cells, monocytes and synoviocytes. A correlation of these molecules with TNFα levels was observed at baseline but not after therapy. These growth factors may be markers of synovial hyperplasia and activity in RA, contributing to inflammatory damage, whereas the amount of plasma mtDNA seems not related to inflammation or disease activity in RA, as also found in SLE.
M.D. - Full Professor of Medicine
University G. D'Annunzio
Clinical assistant, M.D.
SS. Annunziata Hospital, Rheumatology outpatient clinic
Fellow in training, Medicine
SS. Annunziata Hospital, ASL
2Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia
Department of Life Sciences, University of Modena and Reggio Emilia
Full Professor of Immunology, General Pathology
4Department of Medical and Surgical Sciences of Children and Adults, University of Modena and Reggio Emilia