Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria.
Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria.
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DOI：
10.1002/ajh.23885
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发表时间：
2015-03
影响因子：
12.8
通讯作者：
Pavletic SZ
中科院分区：
文献类型：
--
作者：
Kuzmina Z;Gounden V;Curtis L;Avila D;Rnp TT;Baruffaldi J;Cowen EW;Naik HB;Hasni SA;Mays JW;Mitchell S;Baird K;Steinberg SM;Pavletic SZ
在慢性移植物抗宿主病（cGVHD）中发现新的临床生物标志物用于诊断和疾病监测的需求尚未得到满足。循环自身抗体代表一种持续的免疫反应，提示B细胞在cGVHD中起致病作用。自身抗体可能是cGVHD疾病活动性、严重程度或器官特异性的有用标记；然而，它们的临床应用尚未确定。本研究的重点是在一个以NIH标准为特征的大型患者队列中确定一系列临床自身抗体与cGVHD表现的发生率和相关性。在一项横断面前瞻性自然史研究中，对280名cGVHD患者（70%为重度）进行了临床医学中常用的21种循环抗体检测。中位cGVHD持续时间为2年。有循环自身抗体的患者（62%）IgM （P < 0.0001）、IgG （P < 0.0001）和IgA （P = 0.001）水平显著升高，尿酸（P = 0.008）和总蛋白（P = 0.0004）升高，CD31 （P = 0.002）、CD41 （P = 0.001）、CD81 (P = 0.023) T细胞和CD191 B细胞（P < 0.0001）数量显著升高。35%的患者检测到多种抗体。先前的利妥昔单抗治疗（n = 66）与自身抗体的减少相关（48比66% P = 0.01）。在本研究中，只有口服cGVHD与自身抗体存在显著相关（P = 0.028）。cGVHD活性与严重程度和自身抗体存在之间未发现显著关联。循环自身抗体在晚期cGVHD患者中很常见。它们的存在与更好的定量免疫重建有关，但不具有作为cGVHD临床生物标志物的效用。
There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P < 0.0001), IgG (P < 0.0001), and IgA (P = 0.001), elevated uric acid (P = 0.008) and total protein (P = 0.0004), and higher numbers of CD31 (P = 0.002), CD41 (P = 0.001), CD81 (P = 0.023) T cells, and CD191 B cells (P < 0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.
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影响因子：
5.7
作者：
Jounai N;Kobiyama K;Takeshita F;Ishii KJ
通讯作者：
Ishii KJ
影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB
影响因子：
6.5
作者：
DIGHIERO, G;INTRATOR, L;VERNANT, JP
通讯作者：
VERNANT, JP
DOI：
10.4049/jimmunol.1002176
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ota M;Duong BH;Torkamani A;Doyle CM;Gavin AL;Ota T;Nemazee D
通讯作者：
Nemazee D
影响因子：
2.6
作者：
Patriarca, F;Skert, C;Fanin, R
通讯作者：
Fanin, R