ANALYSIS OF NATURAL AND DISEASE-ASSOCIATED AUTOANTIBODY REPERTOIRES - ANTIENDOTHELIAL CELL IGG AUTOANTIBODY ACTIVITY IN THE SERUM OF HEALTHY-INDIVIDUALS AND PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

被引:65
作者
RONDA, N
HAURY, M
NOBREGA, A
KAVERI, SV
COUTINHO, A
KAZATCHKINE, MD
机构
[1] HOP BROUSSAIS,INSERM,U28,F-75014 PARIS,FRANCE
[2] INST PASTEUR,UNITE IMMUNOBIOL,CNRS,URA 359,F-75015 PARIS,FRANCE
关键词
AUTOIMMUNITY; ENDOTHELIAL CELLS; IMMUNOGLOBULIN; REPERTOIRES; SYSTEMIC LUPUS ERYTHEMATOSUS;
D O I
10.1093/intimm/6.11.1651
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The present study demonstrates that natural IgG with anti-endothelial cell activity is present in the serum of healthy individuals and in pooled normal human lg. By using a novel method that allows for the simultaneous and quantitative assessment of reactivities of antibodies with a large number of antigens in tissues, we observed that natural anti-endothelial cell antibody (AECA) recognizes a restricted set of self antigens in endothelial cells that is conserved among healthy individuals. The extent to which natural AECA activity is expressed in serum and the pattern of reactivity of AECA with endothelial cell antigens showed little variability between individuals. Analysis of AECA in the serum of patients with systemic lupus erythematosus (SLE) revealed a higher amount of activity and a wider spectrum of antigenic specificities than that recognized by natural antibodies in endothelial cell extracts. AECA activity of IgG in whole serum was lower than that of purified IgG in the case of healthy individuals and showed little variation among individuals. In contrast, no difference was found between AECA activity of purified IgG and that of IgG in patients' serum, suggesting that SLE sera lack the factors that control expression of AECA activity in the serum of healthy individuals. Our results indicate that natural autoantibodies recognize a restricted and conserved set of self antigens. Our observations further suggest that defective regulation of the expressed autoreactive B cell repertoire is the basis for expansion of novel clonal specificities and enhanced autoantibody activity in serum of patients with autoimmune disease.
引用
收藏
页码:1651 / 1660
页数:10
相关论文
共 37 条
[1]  
ADIB M, 1990, J IMMUNOL, V145, P3807
[2]   NATURAL ANTIBODIES TO FACTOR-VIII (ANTI-HEMOPHILIC FACTOR) IN HEALTHY-INDIVIDUALS [J].
ALGIMAN, M ;
DIETRICH, G ;
NYDEGGER, UE ;
BOIELDIEU, D ;
SULTAN, Y ;
KAZATCHKINE, MD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) :3795-3799
[3]  
AVRAMEAS S, 1991, IMMUNOL TODAY, V12, P154
[4]   AUTOANTIGENIC DETERMINANTS ON HUMAN THYROGLOBULIN .2. DETERMINANTS RECOGNIZED BY AUTOANTIBODIES FROM PATIENTS WITH CHRONIC AUTOIMMUNE-THYROIDITIS COMPARED TO AUTOANTIBODIES FROM HEALTHY-SUBJECTS [J].
BRESLER, HS ;
BUREK, CL ;
HOFFMAN, WH ;
ROSE, NR .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1990, 54 (01) :76-86
[5]  
CHEN C, 1991, J IMMUNOL, V147, P2359
[6]   CHARACTERIZATION OF 2 IMMUNOGLOBULIN VH GENES THAT ARE HOMOLOGOUS TO HUMAN RHEUMATOID FACTORS [J].
CHEN, PP ;
LIU, MF ;
GLASS, CA ;
SINHA, S ;
KIPPS, TJ ;
CARSON, DA .
ARTHRITIS AND RHEUMATISM, 1989, 32 (01) :72-76
[7]  
CRUZ DP, 1991, CLIN EXP IMMUNOL, V85, P254
[8]   NORMAL IMMUNOGLOBULIN-G (IGG) FOR THERAPEUTIC USE (INTRAVENOUS IG) CONTAIN ANTIIDIOTYPIC SPECIFICITIES AGAINST AN IMMUNODOMINANT, DISEASE-ASSOCIATED, CROSS-REACTIVE IDIOTYPE OF HUMAN ANTI THYROGLOBULIN AUTOANTIBODIES [J].
DIETRICH, G ;
KAZATCHKINE, MD .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (03) :620-625
[9]   EVIDENCE FOR A RESTRICTED IDIOTYPIC AND EPITOPIC SPECIFICITY OF ANTITHYROGLOBULIN AUTOANTIBODIES IN PATIENTS WITH AUTOIMMUNE-THYROIDITIS [J].
DIETRICH, G ;
PIECHACZYK, M ;
PAU, B ;
KAZATCHKINE, MD .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (03) :811-814
[10]  
DIGHIERO G, 1983, BLOOD, V62, P264