ADAMTS13-specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura

被引:23
作者
Mancini, Ilaria [1 ,2 ]
Ferrari, Barbara [2 ,3 ]
Valsecchi, Carla [2 ,3 ]
Pontiggia, Silvia [2 ,3 ]
Fornili, Marco [4 ]
Biganzoli, Elia [4 ]
Peyvandi, Flora [1 ,2 ,3 ]
机构
[1] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy
[2] Fdn Luigi Villa, Milan, Italy
[3] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy
[4] Univ Milan, Dept Clin Sci & Community Hlth, Unit Med Stat Biometry & Bioinformat Giulio A Mac, Milan, Italy
关键词
ADAMTS13; protein; Immune complexes; Relapse; Risk factors; Thrombotic thrombocytopenic purpura; ANTI-ADAMTS13; ANTIBODIES; UREMIC SYNDROME; FC-GAMMA; ADAMTS13; DEFICIENCY; RECEPTORS;
D O I
10.1016/j.ejim.2016.11.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy due to the development of autoantibodies against the VWF-cleaving protease ADAMTS13. ADAMTS13-specific circulating immune complexes (CICs) have been described in patients with acquired TTP, but their clinical relevance remained to be established. The aim of this study was to assess the association between ADAMTS13-specific CICs and ADAMTS13-related measurements, clinical and laboratory markers of disease severity, and occurrence of TTP relapse, in autoimmune TTP patients. Material and methods: We measured ADAMTS13-specific CICs in 51 patients with severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, at the first episode of acquired TTP. The associations between ADAMTS13-specific CICs and the variables of interest were assessed by linear, logistic and Cox proportional hazard regression models, where appropriate. Results: The prevalence of ADAMTS13-specific CICs in patients experiencing the first TTP episode was 39% (95% confidence intervals [ CI]: 26-52%). ADAMTS13-specific CICs were not associated neither with laboratory markers of disease severity, nor with patterns of clinical presentation. Conversely, among 45 survivors, a positive association was found between the presence of ADAMTS13-specific CICs and the risk of recurrence within 2 years after the first TTP episode (adjusted hazard ratio, 3.4 [ 95% CI: 0.9 to 13.5]). Conclusions: ADAMTS13-specific CICs seem to be able to predict the recurrence of acute TTP episodes in the first 2 years after disease onset. Therefore, their measurement might be used as a tool to stratify the risk of disease relapse, with potential influence on surveillance and therapeutic choices during remission phase. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:79 / 83
页数:5
相关论文
共 22 条
[1]   Approximate is better than "exact" for interval estimation of binomial proportions [J].
Agresti, A ;
Coull, BA .
AMERICAN STATISTICIAN, 1998, 52 (02) :119-126
[2]   ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura [J].
Bettoni, G. ;
Palla, R. ;
Valsecchi, C. ;
Consonni, D. ;
Lotta, L. A. ;
Trisolini, S. M. ;
Mancini, I. ;
Musallam, K. M. ;
Rosendaal, F. R. ;
Peyvandi, F. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2012, 10 (08) :1556-1565
[3]   IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura [J].
Ferrari, S. ;
Mudde, G. C. ;
Rieger, M. ;
Veyradier, A. ;
Hovinga, J. A. Kremer ;
Scheiflinger, F. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 (10) :1703-1710
[4]   Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura [J].
Ferrari, Silvia ;
Palavra, Kristina ;
Gruber, Bernadette ;
Hovinga, Johanna A. Kremer ;
Knoebl, Paul ;
Caron, Claudine ;
Cromwell, Caroline ;
Aledort, Louis ;
Plaimauer, Barbara ;
Turecek, Peter L. ;
Rottensteiner, Hanspeter ;
Scheiflinger, Friedrich .
HAEMATOLOGICA, 2014, 99 (04) :779-787
[5]   Survival and relapse in patients with thrombotic thrombocytopenic purpura [J].
Hovinga, Johanna A. Kremer ;
Vesely, Sara K. ;
Terrell, Deirdra R. ;
Laemmle, Bernhard ;
George, James N. .
BLOOD, 2010, 115 (08) :1500-1511
[6]   The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases [J].
Karsten, Christian M. ;
Koehl, Joerg .
IMMUNOBIOLOGY, 2012, 217 (11) :1067-1079
[7]  
LACHMANN PJ, 1987, CIBA F SYMP, V129, P149
[8]   Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura [J].
Lotta, L. A. ;
Valsecchi, C. ;
Pontiggia, S. ;
Mancini, I. ;
Cannavo, A. ;
Artoni, A. ;
Mikovic, D. ;
Meloni, G. ;
Peyvandi, F. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2014, 12 (03) :329-336
[9]   FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients [J].
Mancini, Ilaria ;
Valsecchi, Carla ;
Lotta, Luca Andrea ;
Deforche, Louis ;
Pontiggia, Silvia ;
Bajetta, Mariateresa ;
Palla, Roberta ;
Vanhoorelbeke, Karen ;
Peyvandi, Flora .
THROMBOSIS AND HAEMOSTASIS, 2014, 112 (02) :297-303
[10]   Incidence of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome [J].
Miller, DP ;
Kaye, JA ;
Shea, K ;
Ziyadeh, N ;
Cali, C ;
Black, C ;
Walker, AM .
EPIDEMIOLOGY, 2004, 15 (02) :208-215