Journal of Clinical Virology 46 (2009) 43–46 Contents lists available at ScienceDirect Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv Reactivation of human herpesvirus 6 (HHV-6) infection in patients with connective tissue diseases Francesco Broccolo a,∗,2 , Francesco Drago b,2 , Stefania Paolino b , Giulia Cassina c , Francesca Gatto c , Lisa Fusetti d , Barbara Matteoli d , Elisa Zaccaria b , Aurora Parodi b , Paolo Lusso c,e,1 , Luca Ceccherini-Nelli d , Mauro S. Malnati c a Department of Clinical Medicine, Prevention and Biotechnology, University of Milano-Bicocca, Via Cadore, 48, 20052 Monza, Italy b Di.S.E.M, Department of Endocrinologic and Metabolic Sciences, Section of Dermatology, University of Genoa, Italy c Unit of Human Virology, Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy d Department of Experimental Pathology, B.M.I.E, University of Pisa, Italy e Department of Medical Sciences M. Aresu, University of Cagliari, Italy article info Keywords: HHV-6 Viral reactivation Viral load Connective tissue diseases Herpesviruses Real-time PCR abstract Background: Little is known about the involvement of human herpesviruses 6 and 7 (HHV-6 and HHV-7) in autoimmune connective tissue diseases (ACTD). Objective: To determine the prevalence of active infection with HHV-6 and HHV-7 in patients with ACTD. Study design: The presence and quantity of HHV-6 DNA was determined by quantitative real-time PCR in a cross-sectional study of serum, peripheral blood mononuclear cells, and tissues obtained from 58 ACTD patients and 38 healthy subjects (HS). Specific anti-HHV-6 antibody titer was also measured. Results: HHV-6 serum viremia occurred in a significantly higher proportion of ACTD patients compared to HS [26/58 (44.8%) vs. 1/38 (2.6%), p = 0.001] with the highest reactivation frequency [7/10 (70%)] observed in patients with scleroderma. Moreover, HHV-6 in serum was associated with ACTD activity (22/38 vs. 4/20, p < 0.05). Higher titers of HHV-6 antibodies were found in ACTD patients than in HS, although HHV-6 seroprevalence among patients with ACTD and HS was similar. HHV-7 viremia was not detected in any patients or HS controls. Conclusion: The frequent reactivation of HHV-6 in scleroderma and other ACTD, especially when active, suggests that HHV-6 may play a role in the pathogenesis of these diseases. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Autoimmune connective tissue diseases (ACTD) encompass many diseases, including systemic sclerosis or scleroderma (SSc), systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE), dermatomyositis (DM), vasculitis and other conditions caus- ing chronic inflammation that can affect many organs and systems. Although the etiologies of ACTD remain unclear, clinical, epidemio- logical, and laboratory findings suggest that several viral infections may be involved. 1 Reactivation of human herpesvirus 6 (HHV-6), as suggested by the high rates of viral isolation, occurs frequently in patients with collagen vascular diseases. 2 Moreover, Hoffmann and coau- ∗ Corresponding author. Tel.: +39 02 6448 8103; fax: +39 02 6448 8363. E-mail address: francesco.broccolo@unimib.it (F. Broccolo). 1 Present address: Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Mary- land. 2 These authors equally contributed to this work. thors demonstrated active HHV-6 infection in a 37-year-old woman affected by SLE and histiocytic necrotizing lymphadenitis (Kikuchi- Fujimoto disease). 3 More recently, HHV-7 replication has been documented in the salivary glands of patients with adult-onset Still disease. 4 Beside these two reports, little is known about the involve- ment of HHV-6 and 7 in the pathogenesis of ACTD. In the present study the presence and burden of these two viruses in ACTD were investigated. 2. Materials and methods 2.1. Subjects and clinical samples Blood and skin biopsies were obtained from 58 patients with ACTD recruited at the Section of Dermatology, University of Genoa. Their characteristics, details of their therapy, and disease activity are included in Table 1. Disease activity in patients with SLE, LED, DM were assessed using different validated clinical activity tests (SLEDAI, CLASI, DSSI) based on involvement of organs systems. 5–7 1386-6532/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2009.05.010