Cross-Reactivity of Antibodies against Leptospiral Recurrent Uveitis-Associated Proteins A and B (LruA and LruB) with Eye Proteins

被引:41
作者
Verma, Ashutosh [1 ]
Kumar, Pawan [2 ]
Babb, Kelly [1 ]
Timoney, John F. [2 ]
Stevenson, Brian [1 ]
机构
[1] Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40506 USA
[2] Univ Kentucky, Gluck Equine Res Ctr, Lexington, KY USA
基金
美国国家卫生研究院; 美国安德鲁·梅隆基金会;
关键词
ALPHA-CRYSTALLIN; BEHCETS-DISEASE; DOWN-REGULATION; AQUEOUS-HUMOR; EQUINE; HORSES; IDENTIFICATION; AUTOANTIGENS; INTERROGANS; EXPRESSION;
D O I
10.1371/journal.pntd.0000778
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Infection by Leptospira interrogans has been causally associated with human and equine uveitis. Studies in our laboratories have demonstrated that leptospiral lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that antibodies directed against LruA and LruB react with equine lenticular and retinal extracts, respectively. These reactivities were investigated further by performing immunofluorescent assays on lenticular and retinal tissue sections. Incubation of lens tissue sections with LruA-antiserum and retinal sections with LruB-antiserum resulted in positive fluorescence. By employing two-dimensional gel analyses followed by immunoblotting and mass spectrometry, lens proteins cross-reacting with LruA antiserum were identified to be alpha-crystallin B and vimentin. Similarly, mass spectrometric analyses identified beta-crystallin B2 as the retinal protein cross-reacting with LruB-antiserum. Purified recombinant human alpha-crystallin B and vimentin were recognized by LruA-directed antiserum, but not by control pre-immune serum. Recombinant beta-crystallin B2 was likewise recognized by LruB-directed antiserum, but not by pre-immune serum. Moreover, uveitic eye fluids contained significantly higher levels of antiibodies that recognized alpha-crystallin B, beta-crystallin B2 and vimentin than did normal eye fluids. Our results indicate that LruA and LruB share immuno-relevant epitopes with eye proteins, suggesting that cross-reactive antibody interactions with eye antigens may contribute to immunopathogenesis of Leptospira-associated recurrent uveitis.
引用
收藏
页数:9
相关论文
共 46 条
[1]   Behcet's disease: A review [J].
Al-Otaibi, LM ;
Porter, SR ;
Poate, TWJ .
JOURNAL OF DENTAL RESEARCH, 2005, 84 (03) :209-222
[2]   Recurrent uveitis in horses: Vitreal examinations with ultrastructural detection of leptospires [J].
Brandes, K. ;
Wollanke, B. ;
Niedermaier, G. ;
Brem, S. ;
Gerhards, H. .
JOURNAL OF VETERINARY MEDICINE SERIES A-PHYSIOLOGY PATHOLOGY CLINICAL MEDICINE, 2007, 54 (05) :270-275
[3]  
Brem S, 1999, BERL MUNCH TIERARZTL, V112, P390
[4]   OVEREXPRESSION OF THE VIMENTIN GENE IN TRANSGENIC MICE INHIBITS NORMAL LENS CELL-DIFFERENTIATION [J].
CAPETANAKI, Y ;
SMITH, S ;
HEATH, JP .
JOURNAL OF CELL BIOLOGY, 1989, 109 (04) :1653-1664
[5]   Anti-aαB-crystallin immunoreactivity in inflammatory nervous system diseases [J].
Çelet, B ;
Akman-Demir, G ;
Serdaroglu, P ;
Yentür, SP ;
Tasci, B ;
van Noort, JM ;
Eraksoy, M ;
Saruhan-Direskeneli, G .
JOURNAL OF NEUROLOGY, 2000, 247 (12) :935-939
[6]   Associations of seroreactivity against crystallin proteins with disease activity and cataract in patients with uveitis [J].
Chen, Ling ;
Holland, Gary N. ;
Yu, Fei ;
Levinson, Ralph D. ;
Lampi, Kirsten J. ;
Horwitz, Joseph ;
Gordon, Lynn K. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (10) :4476-4481
[7]   Retinitis pigmentosa associated with Fuchs' heterochromic uveitis [J].
Chowers, I ;
Zamir, E ;
Banin, E ;
Merin, S .
ARCHIVES OF OPHTHALMOLOGY, 2000, 118 (06) :800-802
[8]  
COOK CS, 1983, EQUINE VET J, V2, P2
[9]   Inter- and intramolecular epitope spreading in equine recurrent uveitis [J].
Deeg, CA ;
Amann, B ;
Raith, AJ ;
Kaspers, B .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (02) :652-656
[10]   Equine recurrent uveitis is strongly associated with the MHC class 1 haplotype ELA-A9 [J].
Deeg, CA ;
Marti, E ;
Gaillard, C ;
Kaspers, B .
EQUINE VETERINARY JOURNAL, 2004, 36 (01) :73-75