Persistent expression of autoantibodies in SLE patients in remission

被引:105
作者
Yurasov, Sergey
Tiller, Thomas
Tsuiji, Makoto
Velinzon, Klara
Pascual, Virginia
Wardemann, Hedda [1 ]
Nussenzweig, Michel C.
机构
[1] Max Planck Inst Infect Biol, D-10117 Berlin, Germany
[2] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA
[4] Baylor Inst Innunol Res, Dallas, TX 75204 USA
[5] Howard Hughes Med Inst, New York, NY 10021 USA
关键词
D O I
10.1084/jem.20061446
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A majority of the antibodies expressed by nascent B cells in healthy humans are self-reactive, but most of these antibodies are removed from the repertoire during B cell development. In contrast, untreated systemic lupus erythematosus (SLE) patients fail to remove many of the self-reactive and polyreactive antibodies from the naive repertoire. Here, we report that SLE patients in clinical remission continue to produce elevated numbers of self-reactive and polyreactive antibodies in the mature naive B cell compartment, but the number of B cells expressing these antibodies is lower than in patients with active disease. Our finding that abnormal levels of self-reactive mature naive B cells persist in the majority of patients in clinical remission suggests that early checkpoint abnormalities are an integral feature of SLE.
引用
收藏
页码:2255 / 2261
页数:7
相关论文
共 30 条
  • [1] Development of autoantibodies before the clinical onset of systemic lupus erythematosus
    Arbuckle, MR
    McClain, MT
    Rubertone, MV
    Scofield, RH
    Dennis, GJ
    James, JA
    Harley, JB
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (16) : 1526 - 1533
  • [2] Interferon and granulopoiesis signatures in systemic lupus erythematosus blood
    Bennett, L
    Palucka, AK
    Arce, E
    Cantrell, V
    Borvak, J
    Banchereau, J
    Pascual, V
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) : 711 - 723
  • [3] HUMAN LUPUS ANTI-DNA AUTOANTIBODIES UNDERGO ESSENTIALLY PRIMARY V-KAPPA GENE REARRANGEMENTS
    BENSIMON, C
    CHASTAGNER, P
    ZOUALI, M
    [J]. EMBO JOURNAL, 1994, 13 (13) : 2951 - 2962
  • [4] Virus-induced transient bone marrow aplasia: Major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus
    Binder, D
    Fehr, J
    Hengartner, H
    Zinkernagel, RM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (03) : 517 - 530
  • [5] Contribution of receptor editing to the antibody repertoire
    Casellas, R
    Shih, TAY
    Kleinewietfeld, M
    Rakonjac, J
    Nemazee, D
    Rajewsky, K
    Nussenzweig, MC
    [J]. SCIENCE, 2001, 291 (5508) : 1541 - 1544
  • [6] Advances in immunology - Autoimmune diseases
    Davidson, A
    Diamond, B
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (05) : 340 - 350
  • [7] Dörner T, 2001, ARTHRITIS RHEUM-US, V44, P2715, DOI 10.1002/1529-0131(200112)44:12<2715::AID-ART458>3.0.CO
  • [8] 2-L
  • [9] RECEPTOR EDITING - AN APPROACH BY AUTOREACTIVE B-CELLS TO ESCAPE TOLERANCE
    GAY, D
    SAUNDERS, T
    CAMPER, S
    WEIGERT, M
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (04) : 999 - 1008
  • [10] TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease
    Gross, JA
    Johnston, J
    Mudri, S
    Enselman, R
    Dillon, SR
    Madden, K
    Xu, WF
    Parrish-Novak, J
    Foster, D
    Lofton-Day, C
    Moore, M
    Littau, A
    Grossman, A
    Haugen, H
    Foley, K
    Blumberg, H
    Harrison, K
    Kindsvogel, W
    Clegg, CH
    [J]. NATURE, 2000, 404 (6781) : 995 - 999