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1.
J Small Anim Pract ; 64(6): 401-408, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36978210

RESUMEN

OBJECTIVES: To characterise the fever episodes attributed to Shar Pei autoinflammatory disease and to identify common diagnostic and management strategies in the United Kingdom. A secondary objective was to determine risk factors associated with Shar Pei autoinflammatory disease fever episodes. METHODS: A retrospective survey was performed to characterise episodes of Shar Pei autoinflammatory disease fever and to identify commonly used treatments in affected dogs. Clinical data were collected from owners and veterinarians. Frequencies of previously proposed risk factors (skin thickness and folding, muzzle conformation) and comorbid conditions were compared between dogs that had exhibited fever episodes consistent with Shar Pei autoinflammatory disease and those who had not. RESULTS: At least one episode of fever attributed to Shar Pei autoinflammatory disease was reported in 52 of 106 (49%) Shar Pei. Nine other dogs had fever episodes consistent with Shar Pei autoinflammatory disease reported by their owners but not by veterinarians. Median rectal temperature at presentation for Shar Pei autoinflammatory disease fever was 40.1°C [104.2°F] (39.9 to 41.3°C [103.8 to 106.3°F]) and owners reported associated hyporexia (n=33, 63%) and vomiting (n=8, 15%) more frequently than veterinary records (n=22, 42% and n=0, 0%, respectively). The median number of veterinary appointments for Shar Pei autoinflammatory disease was two per dog (1 to 15) while owners reported a median of four episodes per dog per year. None of the assessed phenotypic variants or comorbidities were significantly associated with exhibiting Shar Pei autoinflammatory disease fever episodes. CLINICAL SIGNIFICANCE: Episodes of Shar Pei autoinflammatory disease fever were reported approximately twice as frequently by owners compared to veterinary records, suggesting the burden of this condition may be underestimated by veterinarians. Specific risk factors for Shar Pei autoinflammatory disease fever were not identified.


Asunto(s)
Enfermedades de los Perros , Enfermedades Autoinflamatorias Hereditarias , Animales , Perros , Estudios Retrospectivos , Factores de Riesgo , Enfermedades Autoinflamatorias Hereditarias/veterinaria , Reino Unido/epidemiología , Enfermedades de los Perros/epidemiología
2.
BMC Genomics ; 17: 299, 2016 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-27107962

RESUMEN

BACKGROUND: Dissecting the role copy number variants (CNVs) play in disease pathogenesis is directly reliant on accurate methods for quantification. The Shar-Pei dog breed is predisposed to a complex autoinflammatory disease with numerous clinical manifestations. One such sign, recurrent fever, was previously shown to be significantly associated with a novel, but unstable CNV (CNV_16.1). Droplet digital PCR (ddPCR) offers a new mechanism for CNV detection via absolute quantification with the promise of added precision and reliability. The aim of this study was to evaluate ddPCR in relation to quantitative PCR (qPCR) and to assess the suitability of the favoured method as a genetic test for Shar-Pei Autoinflammatory Disease (SPAID). RESULTS: One hundred and ninety-six individuals were assayed using both PCR methods at two CNV positions (CNV_14.3 and CNV_16.1). The digital method revealed a striking result. The CNVs did not follow a continuum of alleles as previously reported, rather the alleles were stable and pedigree analysis showed they adhered to Mendelian segregation. Subsequent analysis of ddPCR case/control data confirmed that both CNVs remained significantly associated with the subphenotype of fever, but also to the encompassing SPAID complex (p < 0.001). In addition, harbouring CNV_16.1 allele five (CNV_16.1|5) resulted in a four-fold increase in the odds for SPAID (p < 0.001). The inclusion of a genetic marker for CNV_16.1 in a genome-wide association test revealed that this variant explained 9.7 % of genetic variance and 25.8 % of the additive genetic heritability of this autoinflammatory disease. CONCLUSIONS: This data shows the utility of the ddPCR method to resolve cryptic copy number inheritance patterns and so open avenues of genetic testing. In its current form, the ddPCR test presented here could be used in canine breeding to reduce the number of homozygote CNV_16.1|5 individuals and thereby to reduce the prevalence of disease in this breed.


Asunto(s)
Enfermedades Autoinmunes/veterinaria , Variaciones en el Número de Copia de ADN , Enfermedades de los Perros/genética , Reacción en Cadena de la Polimerasa/métodos , Alelos , Animales , Enfermedades Autoinmunes/genética , Perros , Variación Genética , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Homocigoto , Linaje , Reproducibilidad de los Resultados
3.
Clin Immunol Immunopathol ; 74(3): 243-51, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7859414

RESUMEN

A multiple immunodeficiency, involving antibody- and cell-mediated responses in 10 Chinese Shar-Pei (CSP) dogs is described. Abnormal levels of serum IgM and IgA in most cases, and IgG in fewer cases characterized the immunoglobulin deficiencies. Decreased in vitro proliferative responses of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) were found in nine cases. Clinical presentation involved several organ systems and was associated with recurrent infections and malignancy. Sera from affected dogs suppressed PWM-stimulated cell proliferation of affected and normal dogs, but not cultures stimulated with PWM followed by recombinant IL-2 (rIL-2). In vitro supplementation of PBMC cultures with immunomodulatory guanosine analogs (GA) resulted in increased de novo IgG and/or interleukin-6 (IL-6) synthesis. Cells from five immunodeficient dogs showed in vitro evidence of GA- or rIL-2-dependent enhanced immunological responses. Since rIL-2-mediated activation of the IL-2 receptor and GA-mediated immunomodulation are reported to act through protein kinase C (PKC)-independent pathways, it is concluded that the IL-2 receptor is functional in these dogs and that cell activation through alternative pathways may restore immune responses in affected CSP dogs.


Asunto(s)
Linfocitos B/inmunología , Enfermedades de los Perros/inmunología , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/veterinaria , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Animales , Células Cultivadas , Perros
4.
J Hered ; 84(6): 438-42, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8270767

RESUMEN

Renal amyloidosis (RA) and recurrent fever of unknown origin (RFUO) are characteristics of familial Mediterranean fever (FMF), a human disorder inherited as an autosomal-recessive trait. Although no animal model has been established for FMF, a similar syndrome of RFUO and RA has been reported in Chinese Shar-pei (CSP) dogs. This report addresses two questions: (1) Is RA inherited in CSP dogs? (2) If it is, is it possible to hypothesize the type of inheritance involved? Two studies were conducted to answer these questions: a historical cross-sectional comparison, which included CSP and non-CSP dogs with RA; and a prospective study that included CSP dogs with RA, RFUO, or both. The cross-sectional comparison resulted in an odds ratio of 10 for RA in CSP dogs under 7 years of age. The prospective study of 28 dogs with RA or RFUO identified 20 that had RFUO and RA, three with RA alone, and five with RFUO alone. RFUO preceded RA in all cases with both conditions. The RFUO/RA combination was observed in both sexes. Four dogs with RFUO with or without RA were born to parents that either were alive at age 7 or had died because of conditions other than kidney failure/RA. When one parent was known to express one of these conditions, the prevalence of RA was between 25% and 50% among littermates.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Amiloidosis/veterinaria , Enfermedades de los Perros/genética , Enfermedades Renales/veterinaria , Amiloidosis/complicaciones , Amiloidosis/genética , Animales , Estudios Transversales , Modelos Animales de Enfermedad , Perros , Femenino , Fiebre de Origen Desconocido/complicaciones , Fiebre de Origen Desconocido/genética , Fiebre de Origen Desconocido/veterinaria , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/genética , Masculino , Linaje , Estudios Prospectivos , Recurrencia , Especificidad de la Especie
5.
Clin Immunol Immunopathol ; 64(1): 36-45, 1992 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1606750

RESUMEN

Familial Mediterranean Fever (FMF) is a human disorder characterized by recurrent fever of unknown origin (RFUO), renal amyloidosis, and evidence of peritonitis, pleuritis, and/or synovitis. This report suggests that Chinese Shar-pei (CSP) dogs suffer from a similar syndrome. CSP dogs with RFUO (n = 15) showed greater levels of IL-6 in serum than normal controls, hypergammaglobulinemia, and normal or supranormal in vitro lymphocyte blastogenesis in response to mitogen stimulation, when compared to healthy afebrile dogs. In patients 2 years old or older, RFUO was associated with renal failure, renal amyloidosis, and swollen joints. An epidemiological survey of privately owned dogs indicated a RFUO prevalence of 23% in CSP dogs (n = 132) and 1% in dogs of all breeds (n = 98). Increased levels of circulating cytokines, such as IL-6, have been shown to influence such processes as the febrile response, antibody production, and the synthesis of amyloid precursors. We propose that CSP dogs with RFUO, renal amyloidosis, and joint inflammation may serve as an animal model of FMF and that the clinical syndrome is associated with elevated levels of circulating IL-6.


Asunto(s)
Enfermedades de los Perros/fisiopatología , Fiebre Mediterránea Familiar/veterinaria , Fiebre/veterinaria , Interleucina-6/metabolismo , Amiloidosis/patología , Amiloidosis/veterinaria , Animales , Artritis/patología , Artritis/veterinaria , Perros , Calor , Enfermedades Renales/patología , Enfermedades Renales/veterinaria
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