Serum levels of inhibitors of apoptotic proteins (IAPs) change with IVIg therapy in pemphigus.
Serum levels of inhibitors of apoptotic proteins (IAPs) change with IVIg therapy in pemphigus.
复制标题
天疱疮中凋亡蛋白抑制剂 (IAP) 的血清水平随 IVIg 治疗而变化。
DOI：
10.1038/jid.2011.184
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Bystryn,Jean-Claude
中科院分区：
文献类型：
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作者：
Toosi,Siavash;Habib,Nancy;Torres,Genevieve;Reynolds,SandraR;Bystryn,Jean-Claude
天疱疮是一种罕见的自身免疫性水疱疾病，其特征是对表皮附着成分桥蛋白1 （Dsg-1）和桥蛋白3 （Dsg-3; Amagai, 1999）的抗体水平较高。静脉注射Ig （IVIg）降低了这些抗体的水平，以及天疱疮的临床表现，但其作用机制尚不清楚（Czernik et al., 2008）。越来越多的证据表明，天疱疮抗体可导致角质细胞凋亡并导致棘层溶解（Arredondo等人，2005；Li等人，2009；Schmidt和Waschke， 2009）。凋亡蛋白抑制剂（IAPs）可以靶向caspases，其水平的增加导致细胞对凋亡的抵抗（Schimmer, 2004）。IVIg对角化细胞的抗凋亡作用在毒性表皮坏死松解等疾病中是众所周知的（Viard等，1998）。我们在这项研究中的目的是确定IVIg治疗期间血清中IAP水平的变化是否可能是抑制棘层溶解的机制。我们在使用10% IVIg （Gamunex, Talecris biotheraptics, Durham， NC）治疗前后测量了7例活动性天疱疮患者（5例寻常型天疱疮和2例foliaceous天疱疮）血清中的三种IAP （survivin， livin和X-linked IAP (XIAP)）。患者平均年龄59岁（45-74岁）。IVIg每个疗程包括四个周期，每2周给药一次。每个周期为每天400mg kgÀ1，缓慢滴注5天。在4例患者中，IVIg与50-200mg /天的口服环磷酰胺一起使用。所有患者在IVIg治疗前均接受强的松治疗（20-80mg /天）。分别于治疗前、第1、2周、第4 IVIg周期后1、4周采集血清。根据《赫尔辛基原则宣言》，所有患者均给予书面知情同意，该研究得到纽约大学机构审查委员会的批准。测定血清细胞间IgG抗体水平
Pemphigus is a rare autoimmune blistering disease characterized by high levels of antibodies against the epidermal attachment components, desmoglein1 (Dsg-1) and desmoglein3 (Dsg-3; Amagai, 1999). Intravenous Ig (IVIg) reduces the levels of these antibodies, as well as clinical manifestations of pemphigus, but its mechanism of action is unknown (Czernik et al., 2008). There is emerging evidence that pemphigus antibodies can cause keratinocyte apoptosis and contribute to acantholysis (Arredondo et al., 2005; Li et al., 2009; Schmidt and Waschke, 2009). Inhibitors of apoptotic proteins (IAPs) can target the caspases, and increases in their levels lead to resistance to apoptosis (Schimmer, 2004). Antiapoptotic effect of IVIg on keratinocytes is well known in disorders such as toxic epidermal necrolysis (Viard et al., 1998). Our goal in this study was to determine whether IAP levels change in sera during IVIg therapy as a possible mechanism of suppression of acantholysis.We measured three IAPs (survivin, livin, and X-linked IAP (XIAP)) in sera of seven patients with active pemphigus (five pemphigus vulgaris and two pemphigus foliaceus) before and after treatment with 10% IVIg (Gamunex, Talecris Biotherapeutics, Durham, NC). Average age of the patients was 59 (45–74) years. Each course of IVIg consisted of four cycles, administered every 2 weeks. Each cycle consisted of 400 mg kgÀ1 per day infused slowly for 5 days. In four patients, IVIg was administered together with 50–200mg per day of oral cyclophosphamide. All patients were under treatment with prednisone (20–80mg per day) before IVIg therapy. Sera were collected before treatment, 1 and 2 weeks after the first and 1 and 4 weeks after the fourth IVIg cycle. All patients gave written informed consent according to the Declaration of Helsinki Principles, and the study was approved by the New York University Institutional Review Board. Serum levels of intercellular IgG antibodies were measured