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Parvoviral Infection of Endothelial Cells and Its Possible Role in Vasculitis and Autoimmune Diseases

CYNTHIA M. MAGRO, A. NEIL CROWSON, MAGDY DAWOOD, and GERARD J. NUOVO

ABSTRACT.

Objective
. To analyze a series of biopsies from 16 patients who, on the basis of clinical and dermatopathologic findings, had a spectrum of connective tissue diseases (CTD), autoinflammatory or CTD-like syndromes for parvoviral DNA, RNA, and protein.

Methods. Most of the patients were initially screened for parvoviral-related IgG and IgM antibodies. Parvoviral DNA was analyzed by solution phase polymerase chain reaction (PCR). In situ localization of viral VP1 RNA was accomplished by in situ reverse transcriptase (RT) PCR; viral protein (VP2) was detected by immunohistochemistry and these results correlated with the histologic findings. (J Rheumatol 2002;29:xxxx)

Results. Of 11 people tested, 10 had either IgG or IgM specific antibodies against parvovirus. Common histologic features of the 16 cases included an interface dermatitis, interstitial histiocytic infiltration with variable collagen necrobiosis, a mononuclear cell dominant vasculitis, and interstitial neutrophilia. Detection of parvoviral RNA by in situ RT-PCR in 14 of 16 cases corroborated solution phase PCR data and demonstrated that the endothelial cells and surrounding mononuclear cells were the viral target. Viral protein as revealed by immunohistochemisty showed an equivalent histologic distribution. Anti-tumor necrosis factor-a (TNF-a) therapy (etanercept) yielded dramatic improvement after worsening of symptoms with traditional immunosuppressive therapy in the 3 patients in whom this drug was administered; TNF-a mRNA was detected by in situ RT-PCR in the area of parvoviral infected cells.

Conclusion. Parvoviral induced endothelialitis may be responsible for cases of "idiopathic" CTD. (J Rheumatol 2002;29:1227-35)

Key Indexing Terms:

PARVOVIRUS
VASCULITIS
CONNECTIVE TISSUE DISEASE
AUTOIMMUNE DISEASE


From the Department of Pathology, Ohio State University, Columbus, OH, USA; Central Medical Laboratories, Winnipeg, MB, Canada; Regional Medical Laboratories, Tulsa, OK, USA; Cadham Provincial Laboratories, Winnipeg.

Supported by Grant AN3042-GJN from the Lewis Foundation.

C.M. Magro, MD, Professor of Pathology, Ohio State University; A.N. Crowson, MD, Associate Professor of Dermatology, Central Medical Laboratories; M. Dawood, PhD, Cadham Provincial Laboratories; G.J. Nuovo, MD, Professor of Pathology, Ohio State University.

Address reprint requests to Dr. G.J. Nuovo, Department of Pathology, Ohio State University, S305 Rhodes Hall, 450 W 10th Avenue, Columbus, Ohio 43210. E-mail:gnuovomd@pol.net

Submitted July 18, 2001; revision accepted November 8, 2001.




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