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家族性地中海热患者循环中 Annexin A5 水平升高。

Increased levels of circulating Annexin A5 in Familial Mediterranean fever.

机构信息

Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia 7, Hasratyan St,, Yerevan 0014, Armenia.

出版信息

J Inflamm (Lond). 2010 Nov 23;7:55. doi: 10.1186/1476-9255-7-55.

DOI:10.1186/1476-9255-7-55
PMID:21092278
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3002897/
Abstract

BACKGROUND

Familial Mediterranean fever is a genetic autoinflammatory disease most commonly affecting the ethnic groups originating from around the Mediterranean Sea. Apoptosis plays an important role in down-regulation of the inflammatory response by reducing the lifespan of activated immunocompetent cells. Thus, increased apoptosis may be associated with pathogenesis of familial Mediterranean fever.

METHODS

In the present study we determined the serum levels of apoptotic marker, Annexin A5, in familial Mediterranean fever patients, within an attack and attack-free, in comparison to healthy subjects and assessed the influence of colchicine treatment on this parameter. In addition, in all study subjects serum levels of C-reactive protein and interleukine-1β, and the total leukocyte count were also determined.

RESULTS

Our results demonstrated that pathogenesis of familial Mediterranean fever is characterized by the increased levels of circulating Annexin A5, which is higher in patients within the attack and which associate with the increased levels of C-reactive protein and interleukine-1β and total leukocyte count.

CONCLUSIONS

The results obtained indicate elevated rates of apoptosis of subpopulations of leukocytes involved in autoinflammation and recurrent episodes of fever in familial Mediterranean fever. It was also revealed that regular colchicine treatment sufficiently decreases the rate of apoptosis in familial Mediterranean fever patients by affecting the intensity of autoinflammatory reactions.

摘要

背景

家族性地中海热是一种遗传性自身炎症性疾病,主要影响来自地中海周围地区的民族。细胞凋亡通过减少活化免疫细胞的寿命在下调炎症反应中起重要作用。因此,细胞凋亡增加可能与家族性地中海热的发病机制有关。

方法

在本研究中,我们在发作期和无发作期测定了家族性地中海热患者血清中凋亡标志物 Annexin A5 的水平,并与健康受试者进行了比较,并评估了秋水仙碱治疗对该参数的影响。此外,在所有研究对象中还测定了 C 反应蛋白和白细胞介素 1β的血清水平以及白细胞总数。

结果

我们的结果表明,家族性地中海热的发病机制的特征是循环中 Annexin A5 水平升高,在发作期患者中更高,并且与 C 反应蛋白和白细胞介素 1β以及白细胞总数的升高相关。

结论

获得的结果表明,白细胞亚群的凋亡率升高,涉及自身炎症和家族性地中海热的反复发作。还发现,秋水仙碱的常规治疗通过影响自身炎症反应的强度,足以降低家族性地中海热患者的凋亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5af/3002897/f602b9d7e270/1476-9255-7-55-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5af/3002897/2e14f91df605/1476-9255-7-55-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5af/3002897/f602b9d7e270/1476-9255-7-55-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5af/3002897/2e14f91df605/1476-9255-7-55-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5af/3002897/f602b9d7e270/1476-9255-7-55-2.jpg

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本文引用的文献

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Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapy.家族性地中海热的认识进展及靶向治疗的可能性
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Current perspectives on familial Mediterranean fever.家族性地中海热的当前观点
Curr Opin Infect Dis. 2009 Jun;22(3):309-15. doi: 10.1097/QCO.0b013e328329d15e.
3
The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment.
家族性地中海热蛋白(即吡啉)可被半胱天冬酶-1切割,并通过其N端片段激活核因子κB。
Blood. 2008 Sep 1;112(5):1794-803. doi: 10.1182/blood-2008-01-134932. Epub 2008 Jun 24.
4
The role of annexin A5 in the modulation of the immune response against dying and dead cells.膜联蛋白A5在调节针对濒死和死亡细胞的免疫反应中的作用。
Curr Med Chem. 2007;14(3):271-7. doi: 10.2174/092986707779941131.
5
Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome.高IgD血症和周期性发热综合征中外周血淋巴细胞凋亡缺陷。
Blood. 2007 Mar 15;109(6):2416-8. doi: 10.1182/blood-2005-10-039578. Epub 2006 Nov 30.
6
Classical pathway complement activity in Familial Mediterranean fever.家族性地中海热中的经典途径补体活性
Clin Biochem. 2006 Jul;39(7):688-91. doi: 10.1016/j.clinbiochem.2006.02.016. Epub 2006 Apr 24.
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Past, present, and future of annexin A5: from protein discovery to clinical applications.膜联蛋白A5的过去、现在与未来:从蛋白质发现到临床应用
J Nucl Med. 2005 Dec;46(12):2035-50.
8
Clinical significance of measurement of plasma annexin V concentration of patients in the emergency room.急诊室患者血浆膜联蛋白V浓度测定的临床意义
Resuscitation. 2003 May;57(2):171-7. doi: 10.1016/s0300-9572(03)00034-0.
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Mol Cell. 2003 Mar;11(3):591-604. doi: 10.1016/s1097-2765(03)00056-x.
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Increased neutrophil apoptosis during attacks of familial Mediterranean fever.家族性地中海热发作期间中性粒细胞凋亡增加。
Clin Exp Rheumatol. 2001 Sep-Oct;19(5 Suppl 24):S68-71.