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Volume 17, Number 8–August 2011
Seroprevalence of Trichodysplasia Spinulosa–associated Polyomavirus
Author affiliations: Leiden University Medical Center, Leiden, the Netherlands (E. van der Meijden, S. Kazem, M.M. Burgers, J.N. Bouwes Bavinck, M.C.W. Feltkamp); Jeroen Bosch Ziekenhuis, 's Hertogenbosch, the Netherlands (R. Janssens); and National Institute of Public Health and the Environment, Bilthoven, the Netherlands (H. de Melker)
Suggested citation for this article
We identified a new polyomavirus in skin lesions from a patient with trichodysplasia spinulosa (TS). Apart from TS being an extremely rare disease, little is known of its epidemiology. On the basis of knowledge regarding other polyomaviruses, we anticipated that infections with trichodysplasia spinulosa–associated polyomavirus (TSV) occur frequently and become symptomatic only in immunocompromised patients. To investigate this hypothesis, we developed and used a Luminex-based TSV viral protein 1 immunoassay, excluded cross-reactivity with phylogenetically related Merkel cell polyomavirus, and measured TSV seroreactivity. Highest reactivity was found in a TS patient. In 528 healthy persons in the Netherlands, a wide range of seroreactivities was measured and resulted in an overall TSV seroprevalence of 70% (range 10% in small children to 80% in adults). In 80 renal transplant patients, seroprevalence was 89%. Infection with the new TSV polyomavirus is common and occurs primarily at a young age.
Trichodysplasia spinulosa (TS) is a rare disease of the skin seen in solid organ transplant patients receiving immunosuppressive therapy (1–5) and in lymphocytic leukemia patients (4,6–8). A total of 15 TS cases have been described, of which 3 were identified in 2010 (9–11). The disease is characterized by development of follicular papules and keratin spines (spicules) predominantly in the face, often accompanied by alopecia of the eyebrows and eyelashes. Histologically, TS is characterized by abnormal maturation and marked distention of hair follicles. The inner root sheath cells are highly proliferative and contain excessive amount of trichohyalin (1). Transmission electron microscopy showed virus particles 40–45 nm in diameter within these cells (1,4,6).
In plucked spicules of a TS patient, we recently identified a new human polyomavirus virus known as TS-associated polyomavirus (TSV) (9). This finding has been recently confirmed by Matthews et al. (12). Recent analyses by our group have shown high copy numbers of TSV in lesions from other TS patients (S. Kazem and M.C.W. Feltkamp, unpub. data), underscoring the concept that TSV is the causative infectious agent. Phylogenetic analysis showed that TSV forms a tight cluster with a Bornean orangutan polyomavirus and among human polyomaviruses is most closely related to Merkel cell polyomavirus (MCV; also known as MCPyV) (9).
Eight human polyomaviruses have been identified: BKV (13), JCV (14), KIV (15), WUV (16), MCPyV (17), human polyomavirus type 6 (HPyV6) and type 7 (HPyV7) (18), and TSV (9). Infections with BKV and JCV are common and occur primarily in childhood without symptoms, after which the person remains persistently infected. Reactivation occurs only in immunocompromised patients and can cause serious disease, such as BKV-associated nephropathy and progressive multifocal leukoencephalopathy, and probably TS.
In immunocompetent populations, high seroprevalence values of 82%–98% for BKV (19–22) and 39%–77% for JCV (19–22) have been reported. For KIV and WUV identified in airway specimens, calculated seroprevalences are high in the general population (55%–90% and 69%–98%, respectively) (20,21,23,24). For MCPyV, which is present in ≈80% of rare but aggressive cutaneous Merkel cell carcinomas (MCCs) (17,25–27), seroprevalence among healthy persons was shown to be 42%–77% (20,21,28,29). A recent study reported higher serologic responses in MCC patients than in healthy controls (30).
Seroepidemiologic data for BKV, JCV, and MCPyV indicate that human polyomavirus infections are ubiquitous and generally occur without apparent disease. TSV seems to fit this profile, but no seroepidemiologic data to confirm this hypothesis are available. We report development and performance of a multiplex immunoassay to measure seroreactivity against TSV in immunocompetent persons, immunosuppressed persons, and a TS patient. Seroprevalences of TSV infection were calculated for persons of different ages and immune status. We show that TSV is a common infection in the general population and in immunocompromised patients, and discuss the relevance of our findings with respect to TSV-induced disease.
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Suggested Citation for this Article
van der Meijden E, Kazem S, Burgers MM, Janssens R, Bouwes Bavinck JN, de Melker H, et al. Seroprevalence of trichodysplasia spinulosa–associated polyomavirus. Emerg Infect Dis [serial on the Internet]. 2011 Aug [date cited]. http://www.cdc.gov/EID/content/17/8/110114.htm
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Els van der Meijden, Department of Medical Microbiology E4-P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands; email: firstname.lastname@example.org