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1.

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Objectives

Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

Methods

Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

Results

Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

Conclusion

Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.  相似文献   
2.
Clinical symptoms and multiple sleep latency test (MSLT) measures among narcoleptic patients with both cataplexy and HLADR1501 were compared with cataplexy-free narcoleptic patients with a positive finding of HLADR1501 and cataplexy-free patients without HLADR1501. Both mean sleep onset latencies and rapid eye movement (REM) latencies on MSLT were shorter in the patients with cataplexy compared with the cataplexy-free patients. In four cataplexy-free patients without HLADR1501, nocturnal sleep was remarkably long and their excessive daytime sleepiness did not respond to treatment. The findings suggest that the severity and disease mechanism of narcolepsy might become heterogenous when cataplexy and HLADR1501 are considered.  相似文献   
3.
Expression of HLADR, I, i blood group antigen and T6 antigen were studied in Histiocytosis X cells and pulmonary alveolar macrophages using double labelling immunofluorescence technique or immuno-peroxidase procedure. Alveolar macrophages express simultaneously HLADR and i blood group antigen. Histiocytosis X cells, characterized by HLADR and T6 antigens, and by their ultra-structural marker do not express i antigen. These results confirm the hypothesis that histiocytosis X cells constitute a specialized sub-population of the mononuclear phagocyte system.  相似文献   
4.
Maternal - offspring HLA-DRB1 compatibility in multiple sclerosis   总被引:1,自引:0,他引:1  
Major histocompatibility complex (MHC) compatibility has been reported to facilitate the long-term tolerance of fetal or maternally derived stem cells exchanged during pregnancy. Furthermore, such compatibility has been suggested to play a role in fetal viability. An increase in maternal - fetal human leukocyte antigen (HLA) compatibility for class II DR alleles has previously been observed in the autoimmune disease scleroderma. Here, we examined the hypothesis that increased maternal - fetal MHC class II DR compatibility was associated with multiple sclerosis (MS) risk. HLA-DRB1 typing was performed in 2170 affected individuals and 2894 unaffected relatives from 1006 families with MS in at least two members. We found no evidence for increased HLA compatibility between affected individuals and their mothers, compared with unaffected individuals and their mothers, nor compared with affected individuals and their fathers. We also observed no excess of homozygosity of mothers compared with fathers of individuals with MS. In families in which the father shared exactly one allele with the mother, we found no excess in transmission of this allele to affected or unaffected offspring. These findings do not support a role for an excess maternal - fetal HLA-DRB1 compatibility in MS susceptibility.  相似文献   
5.
应用ARMS(amplificationrefractoryrnutationsystem)方法对南京地区100例汉族健康人HLA-DR4进行基因分型,结果表明,本地区汉族人HLA-DR4基因纯合子占6%,杂合子占15%,非DR4占79%。本法较PCR/SSO法简单、快速,结果可靠,可用于HLA配型。检测结果为HLA相关联疾病及人类学的研究提供了参考依据。  相似文献   
6.
以转基因动物研究类风湿关节炎的易感基因   总被引:9,自引:1,他引:8  
目的通过人HLADR4转基因小鼠的胶原性关节炎动物模型研究易感基因对类风湿关节炎及药物治疗的影响。方法将人HLADRα+4β基因转入C57BL/6×DBA/1F1代小鼠复制出转基因动物,并予胶原和佐剂免疫建立胶原性关节炎模型。以分子生物学技术检测外源基因的整合和表达,以发病时间、病理评分及血清Ⅱ型胶原抗体水平研究HLADR4基因对关节炎易感性及甲氨蝶呤治疗的影响。在体外通过淋巴细胞增殖及阻断实验研究Ⅱ型胶原及抗HLADR、Lyt2和L3T4单抗对淋巴细胞增殖的影响。结果①人HLADR4基因稳定整合于C57BL/6×DBA/1F1代小鼠,主要在脾、肾中表达。②HLADR4转基因小鼠对照组发病时间较非转基因小鼠组提早(P<005)。③HLADR4转基因小鼠的对照组总病理评分和软骨破坏评分较相应的甲氨蝶呤治疗组高(P<005),非转基因小鼠的对照组的总病理评分、软骨破坏评分和骨质侵蚀评分较相应的甲氨蝶呤治疗组高(P<005,P<001)。④HLADR4转基因小鼠对照组和甲氨蝶呤治疗组的Ⅱ型胶原抗体水平较相应的非转基因小鼠组高(P<005,P<0001),且均高于二组正常血清对照组(P<  相似文献   
7.
目的研究T淋巴细胞是否参与了急性冠脉综合征(ACS)相关的炎症反应。方法采用流式细胞分析仪分析64例ACS患者和66例健康者循环T淋巴细胞亚群和T细胞激活标志物HLA-DR抗原的表达。结果ACS患者HLA-DR阳性的淋巴细胞数量显著高于健康者。结论ACS患者循环CD4+T淋巴细胞被激活,T细胞参与了ACS的发生。  相似文献   
8.
目的:研究长期高效抗逆转录病毒治疗(HAART)对于人免疫缺陷病毒1型(HIV-1)感染者体内异常免疫激活和免疫重建的影响.方法:德国鲁尔大学艾滋病中心HIV-1感染者55例,在HAART治疗前及HAART治疗后(治疗1、3、5年),检测其外周血中CD4+T,CD8+T,CD8+CD38+T,CD8+HLADR+T细胞和NK细胞数.结果:与健康对照比较,治疗前的HIV-1感染者体内CD4+T和NK细胞数量显著下降(P均<0.05),CD8+T,CD8+HLADR+T细胞数量显著升高(P均<0.05).HAART治疗后CD4+T和NK细胞数回升(P均<0.05),但仍低于正常水平(P<0.05);HAART治疗1年,3年和5年的机体CD4+T细胞数各组间无统计学差异;NK细胞数随HAART治疗进程有下降趋势,1年组和5年组间数据有统计学差异(P<0.05).CD8+HLADR+T细胞数迅速降低减少(P<0.05),治疗前和治疗后各组、3年组和5年组间、1年组和5年组间数据皆有统计学差异(P均<0.05).CD8+CD38+T细胞数HAART治疗前、后,治疗后各组间均无统计学差异.结论:HAART治疗能有效升高免疫细胞数,降低体内异常免疫激活水平,一定程度上实现免疫重建,但即使长期HAART治疗也难以使免疫细胞数恢复到完全正常水平;HLADR对于HAART治疗更敏感;长期HAART治疗过程中HIV-1病毒可能通过某种方式继续损害NK细胞.  相似文献   
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