A prospective,double-blind,randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Using GWAS to identify genetic predisposition in hepatic autoimmunity

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major hepatic autoimmune conditions. Patient morbidity and mortality remain high across these three diseases, and an unmet need for rational therapy exists. Disease understanding has focused on combining clinical and laboratory based science to provide better insights into the joint host and environmental factors necessary for the initiation, and perpetuation, of hepato-biliary inflammation. Twin studies, family studies, population studies and an inter-relationship with other autoimmune phenomena suggest a genetic component to risk for each disease. Until recently, understanding of this genetic risk has been limited to HLA haplotypes. Associations with risk-conferring and protective HLA haplotypes are present in all three diseases. Over the last few years, genome-wide association studies (GWAS), and related genetic association studies, have greatly increased understanding of the genetic risk signature of these three diseases and autoimmunity in general. Here we consider the rationale for GWAS in general and with specific reference to hepatic autoimmunity. We consider the process of GWAS, and highlight major findings to date. Potential functional implications of key findings are discussed including the IL-12/STAT4 pathway in PBC and the CD28/IL-2 pathway in PSC. We describe the marked pleiotropy demonstrated by PBC and PSC, which is consistent with other autoimmune diseases. Further, we focus on specific gene associations including SH2B3, which is common to all three diseases, and FUT2 in PSC, which represents a link between environment and genetics. We review attempts to translate GWAS findings into basic laboratory models including in vivo systems and highlight where clinical observations relate to genetics. Finally we describe deficiencies in GWAS to date and consider future study of genetics in hepatic autoimmunity.     

Use of Sirolimus in the Treatment of Refractory Autoimmune Hepatitis

BackgroundCorticosteroids and azathioprine are widely accepted as the initial therapy for autoimmune hepatitis. However, the disease is refractory to steroids in about 10%-20% of patients, for whom currently there is no standardized treatment. Here we describe our experience with sirolimus in treatment of steroid refractory autoimmune hepatitis.MethodsThis is a longitudinal follow-up study. Between November 2007 and January 2014, 5 subjects with steroid refractory autoimmune hepatitis were treated with sirolimus at our institution.ResultsA response, defined as a sustained >50% fall in alanine aminotransferase (ALT) levels, was achieved in 4/5 patients. A complete response, sustained normalization of ALT levels, was achieved in 2/5 patients. The need for steroids was significantly reduced in all patients (P < .05).ConclusionsIn this small series, sirolimus appears to be useful in the treatment of patients with steroid refractory autoimmune hepatitis.     

IVIG in childhood primary angiitis of the central nervous system: A case report

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy.A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years. Brain computed tomography scans revealed fine calcification in the right temporal and occipital lobes. Brain magnetic resonance imaging scans revealed white matter lesions, with gadolinium enhancement, which waxed, waned, and migrated for 1 year, without immunomodulatory therapies. A cerebrospinal fluid study showed pleocytosis (12 cells per µl). No clinical or serological findings suggested systemic inflammation or vasculitis. Brain angiography was unremarkable. Brain biopsy revealed thickened and hyalinized small vessels, with intramural infiltration of inflammatory cells, which confirmed the diagnosis of small-vessel PACNS. Because the patient developed surgical site infection following biopsy, the administration of monthly IVIG (2 g/kg) was prescribed, instead of immunosuppressive agents. After IVIG therapy, the patient remained stable, except for a single episode of mild radiological exacerbation at 16 months, which occurred when the IVIG interval was expanded. Oral prednisone was added and gradually tapered. At 50 months, his intellectual abilities and motor functions were normal, although he showed residual upper-left homonymous quadrantanopia and post-exercise headache. A temporary headache, associated with the immunoglobulin infusion, was resolved by slowing the infusion rate. PACNS should be treated aggressively to improve prognosis. However, when immunosuppressants are contraindicated, IVIG may be an alternative therapeutic option.     

甲泼尼龙琥珀酸钠对自身免疫性肺气肿模型大鼠氧化应激和抗内皮细胞抗体的影响

目的:研究甲泼尼龙琥珀酸钠对自身免疫性肺气肿模型大鼠氧化应激和抗内皮细胞抗体(AECA)的影响。方法:将雄性SD大鼠随机分为对照组、模型组和干预组,每组8只。除对照组大鼠腹腔注射等体积的完全弗氏佐剂外,模型组和干预组大鼠均腹腔注射体外培养的人脐静脉内皮细胞+完全弗氏佐剂混合物以复制自身免疫性肺气肿模型;造模给药后第2天,干预组大鼠腹腔注射甲泼尼龙琥珀酸钠10 mg/(kg·d),对照组和模型组大鼠均腹腔注射等体积的生理盐水,每日1次,连续21 d。末次给药后,取各组大鼠右肺组织制作石蜡切片并行苏木精-伊红染色,观察肺组织病理变化,测量单位面积内的肺泡数(MAN)和内衬间隔(MLI);检测左肺肺泡灌洗液(BALF)中丙二醛(MDA)、还原型谷胱甘肽(GSH)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,以及BALF和血清中AECA含量。采用Pearson分析模型组大鼠BALF中AECA与MDA、GSH、SOD、GSH-Px的相关性。结果:与对照组比较,模型组大鼠肺组织可见明显的肺气肿病理变化,其MAN显著减少,MLI显著延长(P<0.01);BALF中GSH含量和SOD、GSH-Px活性均显著降低,BALF中MDA含量以及BALF、血清中AECA含量均显著升高(P<0.01)。与模型组比较,干预组大鼠肺组织的肺气肿病理变化明显改善,其MAN显著增加,MLI显著缩短(P<0.01);BALF中GSH含量和SOD、GSH-Px活性均显著升高;BALF中MDA含量以及BALF、血清中AECA含量均显著降低(P<0.01)。模型组大鼠BALF中的AECA与MDA呈正相关(r=0.710,P<0.05),与GSH、SOD、GSH-Px呈负相关(r=-0.754、-0.781、-0.736,P<0.05)。结论:甲泼尼龙琥珀酸钠可能通过减轻氧化应激反应、抑制AECA的表达,从而达到预防自身免疫性肺气肿的目的。     

Screen-detected gallstone disease and autoimmune diseases — A cohort study

BackgroundGallstone disease is highly prevalent and is associated with systemic inflammation.AimsTo determine whether screen-detected gallstones or cholecystectomy are associated with the occurrence of autoimmune and autoinflammatory diseases and the most common subgroups thereof.MethodsA cohort study of three randomly selected general population samples from Copenhagen was performed. Participants (n = 5928) were examined in the period 1982–1992, underwent abdominal ultrasound examination to detect gallstone disease, and followed through national registers until December 2014 (median 24.7 years) for occurrence of immunological diseases. Multivariable Cox regression analyses were performed.ResultsGallstone disease was identified in 10% (591/5928) of participants, of whom 6.8% had gallstones and 3.2% had cholecystectomy at baseline. Gallstone disease was associated with incidence of autoimmune diseases (12.9% versus 7.92%; hazard ratio 1.46; 95% confidence interval [CI], [1.11;1.91]), diabetes mellitus type 1 (5.95% versus 3.67%; 1.53; [1.02;2.30]), and autoimmune thyroid disease (3.70% versus 1.59%; 2.06; [1.26;3.38]). Rheumatoid arthritis, autoinflammatory diseases, or any subgroups thereof were not associated.ConclusionsIn a large general population sample, screen-detected gallstone disease was associated with the development of autoimmune diseases during long-term follow-up. Future research efforts are needed to further explore common disease mechanisms.