A non-allogeneic stimulus triggers the production of de novo HLA antibodies in healthy adults

被引:31
作者
Alberu, Josefina [1 ]
Morales-Buenrostro, Luis E. [2 ]
de Leo, Claudia [1 ]
Vargas-Rojas, Maria Ines [3 ]
Marino-Vazquez, Lluvia A. [2 ]
Crispin, Jose C. [3 ]
机构
[1] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Transplantat, Tlalpan 14000, Mexico
[2] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Tlalpan 14000, Mexico
[3] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Tlalpan 14000, Mexico
关键词
allogeneic; HLA antibodies; PRA; vaccination;
D O I
10.1016/j.trim.2007.06.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Transplant recipients develop antibodies against a wide array of HLA specificities, and not only against the antigens to which they have been exposed. The aim of the present study was to establish if HLA-unrelated immune stimulation is capable of triggering the production of HLA antibodies. Methods: We determined the presence of HLA antibodies in 20 healthy adults before and after the administration of an immune stimulus (hepatitis B vaccine plus tuberculin skin test). HLA antibodies were assessed with a flow-cytometry based system. Results: At baseline, HBsAg antibodies were detected in protective titers in 75% of the subjects; HLA antibodies were negative in all but one. One week after the antigenic stimulus, HBsAg antibody titers increased significantly, without any detectable changes in HLA antibodies. Surprisingly, HLA antibodies developed in 8 participants one month after the application of the stimulus. One additional subject developed HLA antibodies one month later. Therefore 9/20 subjects became PRA positive during the observation period. Antibody specificities were identified by single antigen assay. The alloantibody response elicited by the immune stimulus was not consistent with memory cell stimulation. Conclusions: The findings of this study demonstrate that a non-HLA antigenic stimulus is capable of eliciting the development of HLA antibodies in healthy adults. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:166 / 171
页数:6
相关论文
共 18 条
[1]   Heterologous immunity provides a potent barrier to transplantation tolerance [J].
Adams, AB ;
Williams, MA ;
Jones, TR ;
Shirasugi, N ;
Durham, MM ;
Kaech, SM ;
Wherry, EJ ;
Onami, T ;
Lanier, JG ;
Kokko, KE ;
Pearson, TC ;
Ahmed, R ;
Larsen, CP .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (12) :1887-1895
[2]  
ALBERU J, 2006, AM J TRANSPLANT, V6, P777
[3]   Maintenance of serological memory by polyclonal activation of human memory B cells [J].
Bernasconi, NL ;
Traggiai, E ;
Lanzavecchia, A .
SCIENCE, 2002, 298 (5601) :2199-2202
[4]   Estimating the precursor frequency of naive antigen-specific CD8 T cells [J].
Blattman, JN ;
Antia, R ;
Sourdive, DJD ;
Wang, XC ;
Kaech, SM ;
Murali-Krishna, K ;
Altman, JD ;
Ahmed, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (05) :657-664
[5]   Specificity and degeneracy in antigen recognition: Yin and Yang in the immune system [J].
Eisen, HN .
ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 :1-21
[6]  
LAMBDA IO, 2000, LABSCREEN ANAL SOFTW
[7]   All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies [J].
Lee, PC ;
Terasaki, PI ;
Takemoto, SK ;
Lee, PH ;
Hung, CJ ;
Chen, YL ;
Tsai, A ;
Lei, HY .
TRANSPLANTATION, 2002, 74 (08) :1192-1194
[8]   Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy [J].
Martin, L ;
Guignier, F ;
Mousson, C ;
Rageot, D ;
Justrabo, E ;
Rifle, G .
TRANSPLANTATION, 2003, 76 (02) :395-400
[9]   Clinical relevance of anti-HLA antibodies detected by flow-cytometry bead-based assays - Single-center experience [J].
Mihaylova, Anastassia ;
Baltadjieva, Daniela ;
Boneva, Petia ;
Ivanova, Milena ;
Penkova, Kalina ;
Marinova, Daniela ;
Mihailova, Snejina ;
Paskalev, Emil ;
Simeonov, Petar ;
Naumova, Elissaveta .
HUMAN IMMUNOLOGY, 2006, 67 (10) :787-794
[10]   Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure [J].
Mizutani, K ;
Terasaki, P ;
Rosen, A ;
Esquenazi, V ;
Miller, J ;
Shih, RNJ ;
Pei, R ;
Ozawa, M ;
Lee, J .
AMERICAN JOURNAL OF TRANSPLANTATION, 2005, 5 (09) :2265-2272