Antihistone Autoantibodies in Dobermans With Hepatitis

Background

Immune system involvement is suggested as an underlying cause for Doberman hepatitis (DH) based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of major histocompatibility complex class II antigens, and homozygosity for dog leukocyte antigen DRB1*00601.

Objective

To measure serum antinuclear antibodies (ANA) and serum antihistone antibodies (AHA) in Dobermans with hepatitis. To determine whether increased serum ANA or serum AHA could be used to support the diagnosis of Doberman hepatitis (DH).

Animals

Privately owned 25 subclinically and 13 clinically affected DH Dobermans and 17 healthy control Dobermans.

Methods

Case–control study. Indirect immunofluorescence (IIF) microscopy and line blot tests were employed for the ANA pilot studies and an enzyme‐linked immunosorbent assay (ELISA) assay for detection of IgG AHA.

Results

Indirect immunofluorescence revealed ANA‐positive cases, and line blot showed AHA reactivity. In ELISA, importantly increased concentrations of AHA were found in 92% (23/25) of dogs in the subclinical stage and 84.6% (11 of 13) of dogs in the clinical stage of DH compared with no control dogs (0/17) (P < 0.0005). The mean AHA absorbance values of the blood samples obtained from the 25 subclinical DH dogs (1.36 ± 0.60, mean ± SD) and the 13 clinically affected dogs (1.46 ± 0.49) were significantly higher than in 17 control dogs (0.51 ± 0.18; P < 0.0001).

Conclusions and Clinical Importance

As the presence of AHA indicates autoimmune activity, our results favor an autoimmune background as one cause for DH. Antihistone antibody could represent a novel means for screening Dobermans with increased serum alanine transaminase concentrations and suspicion of DH.     

TGAb、TMAb与合并甲状腺结节的桥本病相关性研究

目的对合并甲状腺结节桥本病（HT）的血清学研究可有助于临床诊断,便于采用不同的治疗方案、合理的手术方式,以减少术后复发率、癌变率及过少腺体保留量可能造成甲状腺功能的严重不足.方法因甲状腺结节行甲状腺手术,术后病理诊断为HT合并甲状腺结节（甲状腺癌、结节性甲状腺肿、甲状腺腺瘤）的患者病例为A组,非HT组为B组.对每组术前血清学TGAB、TMAB检测结果进行统计学比较及分析,探讨每组数据中TGAB、TMAB检测数值对诊断单纯桥本氏甲状腺炎及桥本氏甲状腺炎合并甲状腺结节（甲状腺癌、结节性甲状腺肿、甲状腺腺瘤）有无特异性.结果 A组64例中有46例TGAB、TMAB检测数值呈阳性,阳性率为71.9%;B组318例中有37例阳性病例,阳性率为14.2%.对A、B组及A组各种疾病之间的数据进行统计学比较及分析,数据经检验为正态分布,A、B组之间差异有统计学意义（P〈0.05）,A组各种疾病间无统计学意义（P﹥0.05）.结论本课题对研究甲状腺结节合并HT与非HT血清TGAB、TMAB水平差异有统计学意义,甲状腺结节合并HT的A组各种疾病之间无统计学意义,对甲状腺手术有导向作用.     

Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review

Background

Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed‐restricted disorder.

Hypothesis/Objectives

Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.

Animals

Four dogs with NME.

Methods

Archives from 3 institutions and from 1 author''s (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.

Results

Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.

Conclusions and Clinical Importance

Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.     

Mechanisms of oral tolerance and the treatment of autoimmune diseases

Oral tolerance describes the phenomenon that orally administered proteins induce sys-temic hyporesponsiveness to the protein fed. The primary mechanisms which oral tolerance is mediated include clonal deletion, clonal anergy and active Sue CALT, Low doses favor active suppression cellular suppression through gut associated lymphoid tis-mediated Th2 and Th3 cells, whereas high doses favor deletion and anergy mediated Thl and Th2 cells. Oral tolerance is an effective and specific approach without toxicity. In recent years, it has been used successfully to treat autoimmune diseases in model ani-mals and patients. The article discussed the mechanisms and advances of oral tolerance for the purpose of provid new ways of treat autoimmune diseases.     

Effect of TLR2/4 ligand-enhanced non-specific liver inflammation on autoimmune hepatitis in BALB/c mice

AIM: To explore the role of non-specific liver inflammation in inducing autoimmune hepatitis (AIH) in BALB/c mice.METHODS: The plasmids pCYP2D6, pcDNA3.1 and psTLR2/4 were administered by tail vein injection. The carbon tetrachloride (CCl₄) was injected in the abdominal cavity. The autoimmune response was measured by ELISA. The liver inflammation was observed by HE staining. The liver fibrosis was evaluated by Sirius red staining. RESULTS: CCl₄ induced non-specific liver inflammation in the BALB/c mice, and TLR2/4 ligand enhanced the inflammatory responses. After the repeated injection of CCl₄ stopped, the non-specific liver inflammation disappeared, but CCl₄ promoted autoimmune response, autoimmune hepatitis and liver fibrosis induced by mimetic antigen human CYP2D6, and TLR2/4 ligand enhanced these changes. CONCLUSION: TLR2/4-amplified liver non-specific inflammation may play an important role in the initiation and progression of autoimmune hepatitis in BALB/c mice.     

Hypophysitis,Panhypopituitarism, and Hypothalamitis in a Scottish Terrier Dog

A 6‐year old male neutered Scottish Terrier was referred with a 1 week history of progressive lethargy and anorexia. Neurological examination localized a lesion to the forebrain and hormonal testing showed panhypopituitarism. Magnetic resonance imaging (MRI) of the brain revealed a rounded, well‐defined, suprasellar central mass. The mass was slightly hyperintense to the cortical grey matter on T2‐weighted (T2W), hypointense on T1‐weighted (T1W) images and without T2* signal void. There was a central fusiform enhancement of the mass after contrast administration which raised the suspicion of a pituitary neoplasm. Rapid deterioration of the dog prevented further clinical investigations. Histopathologic examination revealed a lymphocytic panhypophysitis of unknown origin suspected autoimmune involving the hypothalamus (hypothalamitis). This is a unique case report of a dog presenting with inflammatory hypophysitis and hypothalamitis of suspected autoimmune origin with detailed clinical, MRI, histology and immunohistochemistry findings.     

Effect of intravenous injecting plasmid encoding interleukin-19-IgG on experimental autoimmune myocarditis in rats

AIM: To evaluate the effect of intravenous injecting plasmid encoding interleukin-19-IgG on experimental autoimmune myocarditis (EAM) in rats.METHODS: Cardiac myosin was emulsified with equal volume of complete Freund's adjuvant. The animal model of EAM was established by injecting with the preparation in both footpads of the Lewis rats. The rats were intravenously injected with the plasmid encoding IL-19-IgG on day 6. Echocardiography was performed before the rats were sacrificed on day 17. The effect of IL-19-IgG plasmid injection was evaluated by measuring the heart weight/body weight, myocarditis area, relative expression levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the hearts. The mRNA expression levels of related cytokines including IL-18, IL-1β, IL-12p35 and IFN-γ were detected.RESULTS: The rats in model group showed significant myocardial damage and a decrease in the left ventricular functions. The rats in the treatment group injected with IL-19-IgG plasmid showed an improvement of the cardiac functions. The ratio of heart weight/body weight, the area of myocarditis and the mRNA levels of ANP and BNP were significantly lower in IL-19-IgG treatment group than those in model group. The mRNA levels of IL-18, IL-1β, IL-12p35 and IFN-γ were also significantly decreased in IL-19-IgG treatment group.CONCLUSION: Intravenous injection of plasmid encoding IL-19-IgG effectively prevents the development of the left ventricular remodeling and myocardial damage in EAM rats.     

A Review of Candidate Genes for Development of Equine Recurrent Uveitis

Equine recurrent uveitis (ERU) is a serious eye disease and the most common cause of blindness in horses. Until now, the cause of ERU is not fully understood. Persistent infections of pathogenic leptospires have been discussed. Chronic recurrent remitting episodes of inflammations and the positive therapeutic effects of corticosteroids have led to the hypothesis that ERU is an autoimmune disorder. The reason for a dysregulated autoimmune response may be linked to genetic factors. ERU shows similarities to human autoimmune uveitis with a genetic background. An association of the equine leukocyte antigen serological haplotype A9 with ERU in warmblood horses indicated that major histocompatibility complex I (MHCI) influences the development of ERU. The different types of human autoimmune and genetic uveitis, like Behçet's disease, systemic sarcoidosis, Vogt-Koyanagi-Harada syndrome, birdshot retinochoroidopathy, sympathetic ophthalmia, and acute recurrent anterior uveitis, had been associated with the human leukocyte antigen complex and genetic variants of the MHC. Furthermore non-MHC genes with a possible role in autoimmunity may also play a role in ERU-affected horses. The genes presented herein may be of interest for genome-wide association analyses of ERU-affected horses.     

Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand

Abstract

AIMS

To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand.