B Cell Depletion Therapy Exacerbates Murine Primary Biliary Cirrhosis

被引:79
作者
Dhirapong, Amy [1 ]
Lleo, Ana [1 ,2 ]
Yang, Guo-Xiang [1 ]
Tsuneyama, Koichi [3 ]
Dunn, Robert [4 ]
Kehry, Marilyn [4 ]
Packard, Thomas A. [5 ,6 ]
Cambier, John C. [5 ,6 ]
Liu, Fu-Tong [7 ]
Lindor, Keith [8 ]
Coppel, Ross L. [9 ]
Ansari, Aftab A. [10 ]
Gershwin, M. Eric [1 ]
机构
[1] Univ Calif Davis, Sch Med, Div Rheumatol Allergy & Clin Immunol, Genome & Biomed Sci Facil, Davis, CA 95616 USA
[2] Inst Clin Humanitas, Hepatobiliary Immunopathol Unit, Rozzano, Italy
[3] Toyama Univ, Dept Diagnost Pathol, Grad Sch Med & Pharmaceut Sci, Sugitani, Toyama, Japan
[4] Biogen Idec Inc, San Diego, CA USA
[5] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA
[6] Natl Jewish Med & Res Ctr, Denver, CO USA
[7] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA
[8] Mayo Clin Fdn, Div Gastroenterol & Hepatol, Rochester, MN USA
[9] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia
[10] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA
基金
美国国家卫生研究院;
关键词
CHEMICAL XENOBIOTIC IMMUNIZATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LYMPHOCYTE DEPLETION; MOUSE MODEL; AUTOIMMUNE CHOLANGITIS; TARGETED THERAPIES; INDEPENDENT ROLES; IN-VIVO; MICE; DISEASE;
D O I
10.1002/hep.24044
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Primary biliary cirrhosis (PBC) is considered a model autoimmune disease due to the clinical homogeneity of patients and the classic hallmark of antimitochondrial antibodies (AMAs). Indeed, the presence of AMAs represents the most highly directed and specific autoantibody in autoimmune diseases. However, the contribution of B cells to the pathogenesis of PBC is unclear. Therefore, although AMAs appear to interact with the biliary cell apotope and contribute to biliary pathology, there is no correlation of disease severity and titer of AMAs. The recent development of well-characterized monoclonal antibodies specific for the B cell populations, anti-CD20 and anti-CD79, and the development of a well-defined xenobiotic-induced model of autoimmune cholangitis prompted us to use these reagents and the model to address the contribution of B cells in the pathogenesis of murine PBC. Prior to the induction of autoimmune cholangitis, mice were treated with either anti-CD20, anti-CD79, or isotype-matched control monoclonal antibody and followed for B cell development, the appearance of AMAs, liver pathology, and cytokine production. Results of the studies reported herein show that the in vivo depletion of B cells using either anti-CD20 or anti-CD79 led to the development of a more severe form of cholangitis than observed in control mice, which is in contrast with results from several other autoimmune models that have documented an important therapeutic role of B cell specific depletion. Anti-CD20/CD79-treated mice had increased liver T cell infiltrates and higher levels of proinflammatory cytokines. Conclusion: Our results reflect a novel disease-protective role of B cells in PBC and suggest that B cell depletion therapy in humans with PBC should be approached with caution (HEPATOLOGY 2011;53:527-535)
引用
收藏
页码:527 / 535
页数:9
相关论文
共 50 条
[1]   A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis [J].
Agmon-Levin, Nancy ;
Shapira, Yinon ;
Selmi, Carlo ;
Barzilai, Ori ;
Ram, Maya ;
Szyper-Kravitz, Martine ;
Sella, Sara ;
Katz, Bat-sheva Porat ;
Youinou, Pierre ;
Renaudineau, Yves ;
Larida, Bruno ;
Invernizzi, Pietro ;
Gershwin, M. Eric ;
Shoenfeld, Yehuda .
JOURNAL OF AUTOIMMUNITY, 2010, 34 (01) :55-58
[2]   Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells [J].
Allan, Lenka L. ;
Hoefl, Katrin ;
Zheng, Dong-Jun ;
Chung, Brian K. ;
Kozak, Frederick K. ;
Tan, Rusung ;
van den Elzen, Peter .
BLOOD, 2009, 114 (12) :2411-2416
[3]   Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis: Identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid [J].
Amano, K ;
Leung, PSC ;
Rieger, R ;
Quan, C ;
Wang, XB ;
Marik, J ;
Suen, YF ;
Kurth, MJ ;
Nantz, MH ;
Ansari, AA ;
Lam, KS ;
Zeniya, M ;
Matsuura, E ;
Coppel, RL ;
Gershwin, ME .
JOURNAL OF IMMUNOLOGY, 2005, 174 (09) :5874-5883
[4]   Cutting edge:: B cells promote CD8+ T cell activation in MRL-Faslpr mice independently of MHC class I antigen presentation [J].
Chan, OTM ;
Shlomchik, MJ .
JOURNAL OF IMMUNOLOGY, 2000, 164 (04) :1658-1662
[5]   B cells contribute to ischemia/reperfusion-mediated tissue injury [J].
Chen, Jie ;
Crispin, Jose C. ;
Tedder, Thomas F. ;
Lucca, Jurandir Dalle ;
Tsokos, George C. .
JOURNAL OF AUTOIMMUNITY, 2009, 32 (3-4) :195-200
[6]   Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis [J].
Chuang, Ya-Hui ;
Lian, Zhe-Xiong ;
Tsuneyama, Koichi ;
Chiang, Bor-Luen ;
Ansari, Aftab A. ;
Coppel, Ross L. ;
Gershwin, M. Eric .
JOURNAL OF AUTOIMMUNITY, 2006, 26 (04) :232-240
[7]   PRIMARY STRUCTURE OF THE HUMAN M2 MITOCHONDRIAL AUTO-ANTIGEN OF PRIMARY BILIARY-CIRRHOSIS - DIHYDROLIPOAMIDE ACETYLTRANSFERASE [J].
COPPEL, RL ;
MCNEILAGE, LJ ;
SURH, CD ;
VANDEWATER, J ;
SPITHILL, TW ;
WHITTINGHAM, S ;
GERSHWIN, ME .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (19) :7317-7321
[8]   Effect of interleukin-10 on dendritic cell maturation and function [J].
DeSmedt, T ;
VanMechelen, M ;
DeBecker, G ;
Urbain, J ;
Leo, O ;
Moser, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (05) :1229-1235
[9]   Alternatively activated macrophages in infection and autoimmunity [J].
Fairweather, DeLisa ;
Cihakova, Daniela .
JOURNAL OF AUTOIMMUNITY, 2009, 33 (3-4) :222-230
[10]   B cells regulate autoimmunity by provision of IL-10 [J].
Fillatreau, S ;
Sweenie, CH ;
McGeachy, MJ ;
Gray, D ;
Anderton, SM .
NATURE IMMUNOLOGY, 2002, 3 (10) :944-950