IgG Antibodies against Human Cytomegalovirus Late Protein UL94 in the Pathogenesis of Scleroderma-Like Skin Lesions in Chronic Graft Versus Host Disease

• Published in: Blood 2008-11, Vol.112 (11), p.1169-1169
• Main Authors: Pastano, Rocco, Dell'Agnola, Chiara, Bason, Caterina, Gigli, Federica, Rabascio, Cristina, Puccetti, Antonio, Cetto, Gianluigi, Bertolini, Francesco, Peccatori, Fedro Alessandro, Martinelli, Giovanni, Lunardi, Claudio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.1169.1169

Patients undergoing allogeneic cell transplantation (HCT), who develop chronic Graft versus Host Disease (GVHD), can show a cutaneous involvement similar to that of patients with systemic sclerosis (SSc). Human Cytomegalovirus (hCMV) has been shown to be implicated in the pathogenesis of SSc, since a subset of anti-hCMV antibodies directed against the late viral protein UL94, cross-react with the cell surface tetraspanin NAG-2, and induce the vascular and fibrotic damage observed in the disease. HCMV infection and/or its reactivation have also been associated with the increased risk to develop GVHD and with the worsening of clinical manifestations. Immunosuppressive treatment for GVHD can be intuitively correlated to the viral reactivation, however, the pathogenetic link between hCMV infection and chronic GVHD is still lacking. In this study we wanted first to evaluate the presence of anti-hCMV antibodies directed against the viral protein UL94 in the plasma of HCT patients and second to study their possible role in the pathogenesis of chronic GVHD. Eighteen patients undergone allogeneic HCT for hematological malignancies (16 with nonmyeloablative conditioning regimen and 2 with myeloablative), between 2003 and 2006, with a median follow-up of 7.35 months (range 1.2–55.7), were retrospectively studied. Five of them were anti-hCMV antibodies negative but their donors were anti-hCMV IgG positive. Twelve patients experienced hCMV reactivation evaluated by pp65 and PCR and they needed either Gancyclovir or Valgancyclovir or Foscavir as preemptive therapy. Interestingly, almost all patients (11/12) with hCMV reactivation developed chronic GVHD, and six of the eleven had acute GVHD. All GVHD patients showed skin involvement, and some of them had evidence of diffuse skin fibrosis remarkably similar to that of SSc. None of the patients nor of the donors were suffering from autoimmune diseases. Five of 18 are still alive and in complete remission, included the 2 patients with a skin involvement similar to diffuse SSc. One patient with diffuse skin involvement was lost to the follow-up. Thirteen patients died: 8 for progression of disease, 4 because of steroid resistant GVHD, 1 for sepsis and multi-organ failure. Patients who died before day 100 were not suitable for chronic GVHD evaluation. Patients who developed chronic GVHD showed the presence of anti-hCMV derived late viral protein UL94. Remarkably, the 3 patients with chronic GVHD who developed a diffuse SSc-li