Cutaneous Papillomatous Hyperplasia in Cyclosporine-A Treated Beagles

Seibel, Werner; Sundberg, John P.; Lesko, Lawrence J.; Sauk, John J.; McCleary, L. B.; Hassell, Thomas M.

doi:10.1111/1523-1747.ep12277577

Cited by 40 publications

(54 citation statements)

References 27 publications

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“…Canine oral papillomas normally occur in young dogs, have a typical exophytic histologic phenotype, and usually spontaneously regress within 4 to 8 weeks (41). Cutaneous papillomas occur uncommonly in the dog and are caused by a papillomavirus that differs from COPV, suggesting at least a second type of canine papillomavirus (12,33,49,52). Reports describing cutaneous papillomas have primarily been for dogs receiving various forms of immununosuppressive therapy, with the papillomas spontaneously regressing shortly after cessation of the immunosuppressive drug (8,33,49,52).…”

Section: Discussionmentioning

confidence: 99%

“…Cutaneous papillomas occur uncommonly in the dog and are caused by a papillomavirus that differs from COPV, suggesting at least a second type of canine papillomavirus (12,33,49,52). Reports describing cutaneous papillomas have primarily been for dogs receiving various forms of immununosuppressive therapy, with the papillomas spontaneously regressing shortly after cessation of the immunosuppressive drug (8,33,49,52). One study described cutaneous papillomas in a healthy dog that spontaneously regressed 3 weeks after the diagnosis (50).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Goldschmidt¹,

Kennedy

et al. 2006

J Virol

115

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Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (␥c) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the ␥c-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases characterized by the inability to mount humoral and cell-mediated immune responses, and it is invariably fatal within the first 2 years of life (9, 46). X-linked SCID (XSCID) is the most common form of the disease, representing approximately 50% of all human SCID cases (9, 18). XSCID is caused by mutations in the common gamma (␥c) subunit of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 (reviewed in references 4 and 34). Thus, the XSCID phenotype is the complex result of multiple cytokine defects. The shared usage of the ␥c subunit by receptors for growth factors that are critical for normal B-, NK-, and T-cell development and function explains the profound immunologic abnormalities and clinical severity of the disease.Since the first successful HLA-identical bone marrow transplant in a boy with SCID in 1968 (19), bone marrow transplantation (BMT) has become the treatment of choice for all forms of SCID (10,18,22). SCID patients receiving a histocompatible (HLA-identical) BMT have Ͼ90% long-term survival rates (10,18,22). However, the majority of patients do not have a histocompatible donor. Haploidentical (half-matched) BMT with T-cell depletion to prevent fatal graft-versus-host disease has become the standard therapy for SCID patients who lack a histocompatible donor (10,18,22). Although T-cell depletion...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Goldschmidt¹,

Kennedy

et al. 2006

J Virol

115

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“…Severe oral papillomatosis was also seen in a dog with hypogammaglobulinaemia (Bredal et al, 1996), and a further report described multiple cutaneous squamous papillomas associated with IgM deficiency and impaired T-cell responses (Mill and Campbell, 1992). Papillomatosis of the skin (Gregory et al, 1986;Ruehl et al, 1987;Seibel et al, 1989a) and gingiva (Seibel et al, 1989b) was noted as one of several complications of cyclosporin-A therapy; however, no papillomaviral DNA or antigen was demonstrated (Seibel et al, 1989a). Prolonged or severe papillomavirus infections were reported in human patients immunosuppressed by either human immunodeficiency virus infection or iatrogenic means (Stark et al, 1994;Benton and Arends, 1996).…”

Section: Immunity To Papillomavirus Infectionsmentioning

confidence: 99%

Canine Papillomavirus—A Centenary Review

Nicholls

Stanley

1999

Journal of Comparative Pathology

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“…The regressions are associated with a heavy infiltrate of T cells of both CD4 and CD8 phenotypes (1,33,40), and regressions of all lesions occur systemically. Immunosuppression of animals during the periods of papilloma growth has been shown to prolong lesion persistence (29,37,48). HPV-infected lesion regression with an associated immune infiltrate and in situ detectable cytokines has been reported also (17,57).…”

mentioning

confidence: 99%

Combination Treatment with Intralesional Cidofovir and Viral-DNA Vaccination Cures Large Cottontail Rabbit Papillomavirus-Induced Papillomas and Reduces Recurrences

Christensen

Han²,

Cladel³

et al. 2001

Antimicrob Agents Chemother

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. However, recurrences at periods from 1 to 8 weeks after treatment cessation were observed at approximately 50% of cured sites. DNA vaccinations with CRPV E1, E2, E6, and E7 were initiated either after or at the time of intralesional treatments, and the recurrence rates were observed. When DNA vaccinations were started after intralesional cures, recurrence rates were similar to those of vector-vaccinated rabbits. A small proportion of recurrent sites subsequently regressed (4 out of 10, or 40%) in the vaccinated group versus no regression of recurrences in the vectorimmunized group (0 out of 19, or 0%), indicating partial effectiveness. In contrast, when DNA vaccinations were conducted during intralesional treatments, a significant reduction of recurrences (from 10 out of 19, or 53%, of sites in vector-immunized rabbits to 3 out of 20, or 15%, of sites in viral-DNA-immunized rabbits) was observed. DNA vaccination without intralesional treatments had a minimal effect on preexisting papillomas. These data indicated that treatment with a combination of antiviral compounds and specific immune stimulation may lead to long-term cures of lesions without the ensuing problem of papilloma recurrence.Treatment of persistent papillomas with intralesional and topical antiviral compounds and immunomodulators often leads to effective cure of treated lesions in clinical trials with human papillomavirus (HPV) disease (4,5,16,56). However, recurrences are common after treatment cessation (5,6,16,20,56). The reasons for clinical recurrences are unclear, but possible mechanisms include (i) reinfection at adjacent sites, (ii) incomplete destruction of the entire area of active clinical disease, (iii) reactivation of subclinical HPV disease in wounded areas within and adjacent to treated sites, (iv) incomplete activation or induced anergy of antigen-specific cell-mediated immunity to HPV-infected papilloma cells, and (v) genetic factors associated with ineffective host immunity together with antigenic differences between variants of the same HPV type (2,3,9,23,31,46,47,58).There is strong evidence that host immunity to papillomavirus antigens can clear the bulk of HPV and animal papillomavirus infections (reviewed in references 22 and 39). Spontaneous regression of papillomas induced by cottontail rabbit papillomavirus (CRPV), rabbit oral papillomavirus, bovine papillomavirus type 4, and canine oral papillomavirus in rabbits, cattle, and beagles have been observed (8,10,12,34,38,41). The regressions are associated with a heavy infiltrate of T cells of both CD4 and CD8 phenotypes (1,33,40), and regressions of all lesions occur systemically. Immunosuppression of animals during the periods of papilloma growth has been shown to prolong lesion persistence (29,37,48). HPV-infected lesion regression with an associated immune infiltrate and in situ detectable cytokines has been reported also (17,57). The precise effector mechanisms leading to lesion destruction in these clinical infections, however, are unknown. Additional evidence for immu...

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Cutaneous Papillomatous Hyperplasia in Cyclosporine-A Treated Beagles

Cited by 40 publications

References 27 publications

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Canine Papillomavirus—A Centenary Review

Combination Treatment with Intralesional Cidofovir and Viral-DNA Vaccination Cures Large Cottontail Rabbit Papillomavirus-Induced Papillomas and Reduces Recurrences

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