This review summarises the current understanding of immune response and T cell subsets in the context of development of autoimmunity in the dog. Mode of action and rational usage in immune‐mediated disease in the dog are discussed for the following drugs: glucocorticoids, azathioprine, cyclophosphamide, ciclosporin, tacrolimus, human intravenous immunoglobulin, vincristine, danazol, leflunomide, mycophenolate mofetil and liposome‐encapsulated clodronate. Disease mechanisms are discussed and published evidence for drug efficacy is scrutinised for five important immune‐mediated diseases: immune‐mediated haemolytic anaemia, immune‐mediated thrombocytopenia, myasthenia gravis, glomerulonephritis and inflammatory bowel disease. Future strategies for more refined manipulation of adverse immune responses are presented.
BackgroundOutcome prediction in dogs with immune‐mediated hemolytic anemia (IMHA) is challenging and few prognostic indicators have been consistently identified.ObjectivesAn online case registry was initiated to: prospectively survey canine IMHA presentation and management in the British Isles; evaluate 2 previously reported illness severity scores, Canine Hemolytic Anemia Score (CHAOS) and Tokyo and to identify independent prognostic markers.AnimalsData from 276 dogs with primary IMHA across 10 referral centers were collected between 2008 and 2012.MethodsOutcome prediction by previously reported illness‐severity scores was tested using univariate logistic regression. Independent predictors of death in hospital or by 30‐days after admission were identified using multivariable logistic regression.ResultsPurebreds represented 89.1% dogs (n = 246). Immunosuppressive medications were administered to 88.4% dogs (n = 244), 76.1% (n = 210) received antithrombotics and 74.3% (n = 205) received packed red blood cells. Seventy‐four per cent of dogs (n = 205) were discharged from hospital and 67.7% (n = 187) were alive 30‐days after admission. Two dogs were lost to follow‐up at 30‐days. In univariate analyses CHAOS was associated with death in hospital and death within 30‐days. Tokyo score was not associated with either outcome measure. A model containing SIRS‐classification, ASA classification, ALT, bilirubin, urea and creatinine predicting outcome at discharge was accurate in 82% of cases. ASA classification, bilirubin, urea and creatinine were independently associated with death in hospital or by 30‐days.Conclusions and clinical importanceMarkers of kidney function, bilirubin concentration and ASA classification are independently associated with outcome in dogs with IMHA. Validation of this score in an unrelated population is now warranted.
This retrospective study compares the clinical signs and diagnostic findings of 17 canine patients with histopathological diagnoses of idiopathic pericardial effusion (IPE) or pericardial mesothelioma (MS) in order to identify differences in clinical findings or survival times that might aid in premortem differentiation of these disease conditions. Based on this series of cases, clinical signs, physical examination findings and results of non-invasive diagnostic testing are insufficient to differentiate MS from IPE with confidence unless a discrete pericardial or intrapericardial mass can be identified. Surgical biopsy may be misleading if large amounts of highly reactive and invasive mesothelial cells are seen. Recurrence of significant amounts of pleural effusion within 120 days of pericardiectomy may increase the likelihood that MS is the cause of pericardial effusion in cases in which other causes have been excluded. Survival longer than 120 days postpericardiectomy without chemotherapeutic intervention is associated with a decreased probability of the condition being MS.
A case of angiostrongylosis is described in a 14-month-old golden retriever bitch. Conjunctival haemorrhage and neurological signs, referable to a space-occupying cerebral lesion, were associated with defective primary haemostasis caused by low levels of von Willebrand factor. Full clinical recovery followed treatment with desmopressin, fresh whole blood transfusion, fenbendazole and supportive care. The magnetic resonance image of the suspected organising haematoma is described. Similarities to the human condition, acquired von Willebrand syndrome, and a possible role for aberrant larval migration in haematoma formation are suggested.
Intranasal administration of peptide Ac1–9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4+ T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-TReg) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo. In addition, the expression of suppressor of cytokine signaling 3 was induced in tolerant T cells, suggesting that cytokines regulate the tolerant state of the PI-TReg cells. Stimulation of PI-TReg cells in vitro with IL-10 induced Jak1 and STAT3 activation, but not STAT5, suggesting that IL-10 is important, but not the only cytokine involved in the development of T cell tolerance. Although IL-2 expression was deficient, stimulation with IL-2 in vitro induced Jak1 and STAT5 activation in PI-TReg cells, restored their proliferative response to antigenic stimulation, and abrogated PI-TReg-mediated suppression in vitro. However, the addition of IL-2 could not suppress IL-10 expression, and the IL-2 gene remained inactive. After withdrawal of IL-2, the PI-TReg cells regained their nonproliferative state and suppressive ability. These results underline the ability of the immune system to maintain tolerance to autoantigens, but at the same time having the ability to overcome the suppressive phenotype of tolerant T cells by cytokines, such as IL-2, during the protective immune response to infection.
Thoracoscopic pericardial window is of low morbidity with short surgery and hospitalisation times. It provides good long-term control of idiopathic pericardial effusion but short-term palliation of clinical signs in dogs with neoplastic disease.
A retrospective study was performed to investigate the frequency of identification and characteristics of oesophageal disease in cats, including assessment of the utility of diagnostic techniques and clinical outcome. Thirty-three cats met the inclusion criteria, giving an in-clinic frequency of 33/2894 (approximately 1%) of feline referral cases. Vomiting and/or regurgitation were the most common presenting signs described, although a number of cats (6/33) showed neither. Useful diagnostic modalities included plain radiography, fluoroscopy, barium radiography and endoscopy. A wide range of diseases was reported including congenital disease, oesophagitis, foreign body obstruction, neoplasia, extraluminal compression and hypomotility disorder. Five of six cats with acquired oesophageal strictures had recently received doxycycline per os.
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