Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis

被引:53
作者
Pianta, Annalisa [1 ]
Drouin, Elise E. [1 ]
Crowley, Jameson T. [1 ]
Arvikar, Sheila [1 ]
Strle, Klemen [1 ]
Costello, Catherine E. [2 ]
Steere, Allen C. [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA
[2] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA
关键词
Annexin A2; Autoantigen; Lyme arthritis; Lyme disease; Borrelia burgdorferi; GROWTH-FACTOR; AUTOANTIBODIES; AUTOANTIGEN; RECEPTOR; IDENTIFICATION; PLASMINOGEN; ANTIBODIES; BIOLOGY; FLUID;
D O I
10.1016/j.clim.2015.07.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (IA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:336 / 341
页数:6
相关论文
共 38 条
[1]   Anti-annexin II antibody is associated with thrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis [J].
Ao, Wen ;
Zheng, Hui ;
Chen, Xiao-Wei ;
Shen, Yan ;
Yang, Cheng-De .
RHEUMATOLOGY INTERNATIONAL, 2011, 31 (07) :865-869
[2]   Unraveling Lyme Disease [J].
Bockenstedt, Linda K. ;
Wormser, Gary P. .
ARTHRITIS & RHEUMATOLOGY, 2014, 66 (09) :2313-2323
[3]   Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome [J].
Cesarman-Maus, Gabriela ;
Rios-Luna, Nina P. ;
Deora, Arunkumar B. ;
Huang, Bihui ;
Villa, Rosario ;
Cravioto, Maria del Carmen ;
Alarcon-Segovia, Donato ;
Sanchez-Guerrero, Jorge ;
Hajjar, Katherine A. .
BLOOD, 2006, 107 (11) :4375-4382
[4]   Annexin A2: biology and relevance to the antiphospholipid syndrome [J].
Cockrell, E. ;
Espinola, R. G. ;
McCrae, K. R. .
LUPUS, 2008, 17 (10) :943-951
[5]   Plasminogen is required for efficient dissemination of B-burgdorferi in ticks and for enhancement of spirochetemia in mice [J].
Coleman, JL ;
Gebbia, JA ;
Piesman, J ;
Degen, JL ;
Bugge, TH ;
Benach, JL .
CELL, 1997, 89 (07) :1111-1119
[6]  
Crowley J.T., 2015, J INFECT DIS
[7]   Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease [J].
Dominguez-Villar, Margarita ;
Baecher-Allan, Clare M. ;
Hafler, David A. .
NATURE MEDICINE, 2011, 17 (06) :673-675
[8]   A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease [J].
Drouin, Elise E. ;
Seward, Robert J. ;
Strle, Klemen ;
McHugh, Gail ;
Katchar, Kianoosh ;
Londono, Diana ;
Yao, Chunxiang ;
Costello, Catherine E. ;
Steere, Allen C. .
ARTHRITIS AND RHEUMATISM, 2013, 65 (01) :186-196
[9]   Evolving concepts of rheumatoid arthritis [J].
Firestein, GS .
NATURE, 2003, 423 (6937) :356-361
[10]   Annexins:: Linking Ca2+ signalling to membrane dynamics [J].
Gerke, V ;
Creutz, CE ;
Moss, SE .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (06) :449-461