A Natural Canine Homologue of Alopecia Areata in Humans
A Natural Canine Homologue of Alopecia Areata in Humans
Background: Alopecia areata (AA) is suspected to be an autoimmune disease directed preferentially against hair follicles (HF) affecting both humans and various mammalian species. Recently, two rodent models of AA were described, namely the ageing C3H/HeJ mouse and the DEBR rat. Despite several case reports of canine AA in the literature, there has been no systematic assessment of the disease in these companion animals, and it is also not known whether dogs with AA could be useful as an outbred homologue of this disease in humans.
Objectives: To evaluate the clinical, histopathological and immunopathological features of 25 dogs with AA and compare these data with those found in the human disease.
Patients/methods: Twenty-five client-owned dogs exhibiting macroscopic alopecia with peri- or intrabulbar lymphocytic infiltrates were selected for study. Biopsies and sera were obtained and assessed by histopathology, direct immunofluorescence of immunoreactant deposition, immunohistochemistry for lymphocyte markers, indirect immunofluorescence and immunoblotting analysis of circulating serum IgG, selective immunoprecipitation of HF proteins by serum IgG, and passive transfer of purified canine IgG into naĂ¯ve C57BL/10 mice.
Results: Clinical signs including alopecia, skin hyperpigmentation and leucotrichia usually developed during adulthood and were first seen on the face, followed by the forehead, ears and legs. Spontaneous remission of alopecia occurred in 60% of dogs and regrowing hair shafts were often non-pigmented. Histological examination of skin biopsy specimens revealed peri- and intrabulbar mononuclear cell infiltrates affecting almost exclusively anagen HF. Direct immunofluorescence analysis detected HF-specific IgG in 73% of dogs, while indirect immunofluorescence revealed circulating IgG autoantibodies to the HF inner and outer root sheaths, matrix and precortex. Immunoblotting analysis revealed IgG reactivity to proteins in the 45-60 kDa molecular weight range and with a 200-220 kDa doublet. The latter was identified as trichohyalin by selective immunoprecipitation. Purified HF-reactive IgG, pooled from AA-affected dogs, was injected intradermally to the anagen skin of naĂ¯ve mice where it was associated with the local retention of HFs in an extended telogen phase in AA-treated skin compared with that seen in controls.
Conclusions: These findings are very similar to those reported for human AA patients; therefore, they support the consideration of dogs with AA as a useful homologue for the study of the pathogenesis of this common autoimmune disease of humans.
Alopecia areata (AA) is a common cause of hair loss, afflicting at least 1-2% of the general population, where it commonly manifests as patchy areas of complete hair loss on the scalp and other body parts. In some cases AA can progress to complete loss of all body hair. AA results from selective, largely reversible, damage to anagen hair follicles (HFs). While the aetiology of AA is still rather vague, most agree that an immune-mediated pathogenesis is probably involved, based on several indirect and direct observations. One of the most consistent and reproducible immunological abnormalities in AA is a dense peribulbar lymphocytic infiltrate primarily affecting early anagen HFs. Several of the requirements for ascribing autoimmune status to AA now appear to be in place. Not only can the disease be passively transferred by T cells, serum IgG may also disturb hair cycling. There is also evidence that hair bulb melanocytes could express relevant target antigens. Moreover, it appears that the autoimmune response to HFs recedes rather than follows the disease process. Other indirect clues for autoimmunity include the association of the disease with particular human leucocyte antigen (HLA) haplotype(s), other autoimmune diseases and a response to immunosuppressive therapies.
AA is also expressed in non-human mammals and a recent comparative analysis of AA-like hair disorders revealed remarkable similarities between human and non-human AA in terms of clinical presentation, histology, and cellular or humoral immunity. In fact, a major spur in recent AA research was provided by the development of two animal models for human AA: the inbred rodent models of the C3H/HeJ mouse and the DEBR rat. Both models have provided very useful data not only on the genetics of AA but also on the associated immune perturbations and the assessment of various treatment options.
Recently, we described a dog with AA-like hair loss characterized by infiltration of HF with intrabulbar cytotoxic T lymphocytes and demonstrated that this was associated with the alopecia. Moreover, in a recent study of four dogs with progressive, non-scarring, AA-like hair loss we reported that the sera of these dogs contained anti-HF IgG, some of which targeted trichohyalin, the protein associated with the intermediate filaments plentiful in the inner root sheath (IRS). Others have reported cases of AA or AA-like disease in domestic animals including dogs and horses. The limited characterization of many of these cases, however, prevents assessment of their scientific or clinical value. None the less, animal models, including outbred animals, are likely to be valuable for the dissection of the common pathways underlying the pathogenesis of AA and for the development and evaluation of therapies for AA. While AA appears to be a rare condition in domestic dogs, its true incidence could be much higher as mild forms are likely to go unreported.
Here we report clinical, histopathological and immunopathological findings in a large group of unrelated dogs that provides new and supporting evidence for AA being a suitable homologue for the human disease.
Background: Alopecia areata (AA) is suspected to be an autoimmune disease directed preferentially against hair follicles (HF) affecting both humans and various mammalian species. Recently, two rodent models of AA were described, namely the ageing C3H/HeJ mouse and the DEBR rat. Despite several case reports of canine AA in the literature, there has been no systematic assessment of the disease in these companion animals, and it is also not known whether dogs with AA could be useful as an outbred homologue of this disease in humans.
Objectives: To evaluate the clinical, histopathological and immunopathological features of 25 dogs with AA and compare these data with those found in the human disease.
Patients/methods: Twenty-five client-owned dogs exhibiting macroscopic alopecia with peri- or intrabulbar lymphocytic infiltrates were selected for study. Biopsies and sera were obtained and assessed by histopathology, direct immunofluorescence of immunoreactant deposition, immunohistochemistry for lymphocyte markers, indirect immunofluorescence and immunoblotting analysis of circulating serum IgG, selective immunoprecipitation of HF proteins by serum IgG, and passive transfer of purified canine IgG into naĂ¯ve C57BL/10 mice.
Results: Clinical signs including alopecia, skin hyperpigmentation and leucotrichia usually developed during adulthood and were first seen on the face, followed by the forehead, ears and legs. Spontaneous remission of alopecia occurred in 60% of dogs and regrowing hair shafts were often non-pigmented. Histological examination of skin biopsy specimens revealed peri- and intrabulbar mononuclear cell infiltrates affecting almost exclusively anagen HF. Direct immunofluorescence analysis detected HF-specific IgG in 73% of dogs, while indirect immunofluorescence revealed circulating IgG autoantibodies to the HF inner and outer root sheaths, matrix and precortex. Immunoblotting analysis revealed IgG reactivity to proteins in the 45-60 kDa molecular weight range and with a 200-220 kDa doublet. The latter was identified as trichohyalin by selective immunoprecipitation. Purified HF-reactive IgG, pooled from AA-affected dogs, was injected intradermally to the anagen skin of naĂ¯ve mice where it was associated with the local retention of HFs in an extended telogen phase in AA-treated skin compared with that seen in controls.
Conclusions: These findings are very similar to those reported for human AA patients; therefore, they support the consideration of dogs with AA as a useful homologue for the study of the pathogenesis of this common autoimmune disease of humans.
Alopecia areata (AA) is a common cause of hair loss, afflicting at least 1-2% of the general population, where it commonly manifests as patchy areas of complete hair loss on the scalp and other body parts. In some cases AA can progress to complete loss of all body hair. AA results from selective, largely reversible, damage to anagen hair follicles (HFs). While the aetiology of AA is still rather vague, most agree that an immune-mediated pathogenesis is probably involved, based on several indirect and direct observations. One of the most consistent and reproducible immunological abnormalities in AA is a dense peribulbar lymphocytic infiltrate primarily affecting early anagen HFs. Several of the requirements for ascribing autoimmune status to AA now appear to be in place. Not only can the disease be passively transferred by T cells, serum IgG may also disturb hair cycling. There is also evidence that hair bulb melanocytes could express relevant target antigens. Moreover, it appears that the autoimmune response to HFs recedes rather than follows the disease process. Other indirect clues for autoimmunity include the association of the disease with particular human leucocyte antigen (HLA) haplotype(s), other autoimmune diseases and a response to immunosuppressive therapies.
AA is also expressed in non-human mammals and a recent comparative analysis of AA-like hair disorders revealed remarkable similarities between human and non-human AA in terms of clinical presentation, histology, and cellular or humoral immunity. In fact, a major spur in recent AA research was provided by the development of two animal models for human AA: the inbred rodent models of the C3H/HeJ mouse and the DEBR rat. Both models have provided very useful data not only on the genetics of AA but also on the associated immune perturbations and the assessment of various treatment options.
Recently, we described a dog with AA-like hair loss characterized by infiltration of HF with intrabulbar cytotoxic T lymphocytes and demonstrated that this was associated with the alopecia. Moreover, in a recent study of four dogs with progressive, non-scarring, AA-like hair loss we reported that the sera of these dogs contained anti-HF IgG, some of which targeted trichohyalin, the protein associated with the intermediate filaments plentiful in the inner root sheath (IRS). Others have reported cases of AA or AA-like disease in domestic animals including dogs and horses. The limited characterization of many of these cases, however, prevents assessment of their scientific or clinical value. None the less, animal models, including outbred animals, are likely to be valuable for the dissection of the common pathways underlying the pathogenesis of AA and for the development and evaluation of therapies for AA. While AA appears to be a rare condition in domestic dogs, its true incidence could be much higher as mild forms are likely to go unreported.
Here we report clinical, histopathological and immunopathological findings in a large group of unrelated dogs that provides new and supporting evidence for AA being a suitable homologue for the human disease.
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