Seroprevalence of trichodysplasia spinulosa-associated polyomavirus

Abstract

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.

Figure 1

Reproducibility of trichodysplasia spinulosa–polyomavirus (TSV) viral protein 1 (VP1) immunoassay. Seroreactivity against TSV VP1 in 80 renal transplant patients, the Netherlands, was analyzed twice by using the Bio-Plex 100 analyzer (Bio-Rad Laboratories, Hercules, CA, USA). Datasets 1 and 2 were obtained during a 3-month interval by using freshly coupled identical glutathione–casein bead sets coupled independently with the same crude TSV VP1 bacterial extract. Each circle represents 1 serum sample, and the line represents results of linear regression analyses. Correlation coefficient (r²) was determined by using GraphPad Prism software (GraphPad Software Inc., La Jolla, CA, USA). MFI, median fluorescent intensity.

Figure 2

Cross-reactivity between trichodysplasia spinulosa–polyomavirus (TSV), Merkel cell polyomavirus (MCV), and BKV polyomavirus viral protein 1 (VP1). Correlation between seroreactivity against TSV VP1 and MCV VP1 (A) and BKV VP1 (B) was analyzed by using Bio-Plex 100 analyzer (Bio-Rad Laboratories, Hercules, CA, USA) with 30 serum samples from renal transplant patients, the Netherlands. Each circle represents 1 serum sample, and the line represents results of linear regression analyses. Correlation coefficients (r²) were determined by using GraphPad Prism software (GraphPad Software Inc., La Jolla, CA, USA). MFI, median fluorescent intensity.

Figure 3

Cross-competition between trichodysplasia spinulosa–associated polyomavirus (TSV) and Merkel cell polyomavirus (MCV) viral protein 1 (VP1) in serial dilutions of serum samples RTR 108 and RTR 128 from renal transplant recipient patients reactive against TSV VP1 and MCV VP1, the Netherlands. Reactivity was determined by using the VP1 multiplex antibody-binding assay. Samples were preincubated with soluble recombinant glutathione-S-transferase (GST) (black line), GST-MCV VP1 (red line), or GST-TSV VP1 (blue line). Values are median fluorescent intensity (MFI) for seroreactivity against TSV VP1 (A and B) or MCV VP1 (C and D).

Figure 4

Cross-competition between trichodysplasia spinulosa–associated polyomavirus (TSV) and BKV polyomavirus viral protein 1 (VP1) in serial dilutions of serum samples RTR 141 and RTR 329 from renal transplant recipient patients reactive against TSV VP1 and BKV VP1, the Netherlands. Reactivity was determined by using the VP1 multiplex antibody-binding assay. Samples were preincubated with soluble recombinant glutathione-S-transferase (GST) (black line), GST-BKV VP1 (red line), or GST-TSV VP1 (blue line). Values are median fluorescent intensity (MFI) for seroreactivity against TSV VP1 (A and B) or BKV VP1 (C and D).

Figure 5

Seroresponses against trichodysplasia spinulosa–associated polyomavirus (TSV) (A) and BKV polyomavirus (B) for a patient with trichodysplasia spinulosa, the Netherlands. Serial dilutions of serum from a TS patient were tested for reactivity against TSV viral protein 1 (VP1) or BKV VP1 by using the VP1 multiplex antibody-binding assay. Samples were preincubated with soluble recombinant glutathione-S-transferase (GST) (black line), GST-BKV VP1 (red line), or GST-TSV VP1 (blue line). MFI, median fluorescent intensity.

Figure 6

Seroresponses to trichodysplasia spinulosa–associated polyomavirus (TSV) and BKV polyomavirus in healthy and immunocompromised populations, the Netherlands. Serum samples were obtained from 528 healthy persons (PrePIENTER) and 80 renal transplant recipients (RTR) and screened for reactivity against TSV viral protein 1 (VP1) (A) and BKV VP1 (B) by using the VP1 multiplex antibody-binding assay. Each circle represents 1 sample, and horizontal lines represent cutoff values. Percentage values indicate seropositivity. MFI, median fluorescent intensity.

Figure 7

Age-related seroprevalence of trichodysplasia spinulosa–associated polyomavirus (TSV) viral protein 1 (VP1) (A) and BKV polyomavirus VP1 (B) in a healthy population, the Netherlands. The population was divided into 8 age groups: <1–9 years of age (n = 79), 10–19 (n = 66), 20–29 (n = 51), 30–39 (n = 64), 40–49 (n = 76), 50–59 (n = 54), 60–69 (n = 79), and 70–79 (n = 56). Each circle represents 1 serum sample, and the horizontal lines represent cutoff values. MFI, median fluorescent intensity. C) Seroprevalence of TSV VP1 (white bars) and BKV VP1 (gray bars), by age. D) Seroprevalence of TSV VP1 and BKV VP1 in youngest age group. Population was divided into 5 smaller age groups: 1–2 years of age (n = 10); 3–4 (n = 18); 5–6 (n = 22); 7–8 (n = 17); 9–10 (n = 16). Error bars indicate 95% confidence intervals.