Molecular aspects and the pathological basis of primary biliary cirrhosis

Journal of Autoimmunity

Volumn 9, Issue 2, 1996, Pages 119-128

  Leung, Patrick S C ^a   Van De Water, Judy ^a   Coppel, Ross L ^b   Nakanuma, Yasuni ^c   Munoz, Santiago ^d   Gershwin, M Eric ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b MONASH UNIVERSITY   (Australia)

^c KANAZAWA UNIVERSITY   (Japan)

^d ALBERT EINSTEIN MEDICAL CENTER   (United States)

Author keywords

2 oxo acid dehydrogenase complex; Anti mitochondrial autoantibodies; Biliary epithelial cells; Combinatorial autoantibodies; Cross reactive molecule; HLA antigens; Ig genes; PDC E2; T cells

Indexed keywords

2 OXOACID DEHYDROGENASE; AUTOANTIBODY; HLA ANTIGEN; MITOCHONDRION ANTIBODY;

DNA SEQUENCE; HUMAN; IMMUNOGLOBULIN GENE; PATHOPHYSIOLOGY; PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE;

EID: 0029945543     PISSN: 08968411     EISSN: None     Source Type: Journal    
DOI: 10.1006/jaut.1996.0015     Document Type: Review

References (103)

1. Kaplan M.M. 1987. Primary biliary cirrhosis. (Review) Advances in Internal Medicine 32: 359-377
2. James S.P. 1990. Primary biliary cirrhosis and primary sclerosing cholangitis. Igaku Shoin, New York
3. Mackay I.R., Gershwin M.E. 1990. Primary biliary cirrhosis: considerations on pathogenesis based on identification of the M2 autoantigens. Semin. Immunopathol. 12: 101-119
4. Lindenborn-Fotinos J., Baum H., Berg P.A. 1985. Mitochondrial antibodies in primary biliary cirrhosis: species and nonspecies specific determinants of M2 antigen. Hepatology 5: 763-769
5. Lindenborn-Fotinos J., Sayers T.J., Berg P.A. 1982. Mitochondrial antibodies in primary biliary cirrhosis. VI. Association of the complement fixing antigen with a component of the mitochondrial F1-ATPase complex. Clinical & Experimental Immunology 50: 267-274
6. Berg P.A., Klein R., Lindenborn-Fotinos J., Kloppel W. 1982. ATPase-associated antigen (M2): marker antigen for serological diagnosis of primary biliary cirrhosis. Lancet 2: 1423-1426
7. Berg P.A., Klein R. 1986. Mitochondrial antigens and autoantibodies: from anti-M1 to anti-M9. Klinische Wochenschrift 64: 897-909
8. Berg P.A., Klein R. 1987. Immunology of primary biliary cirrhosis. (Review) Baillieres Clinical Gastroenterology 1: 675-706
9. Ghadiminejad I., Baum H. 1987. Reaction pattern of mitochondrial antibodies of primary biliary cirrhosis (PBC) is species specific but not organ specific. Journal of Bioenergetics & Biomembranes 19: 239-253
10. Mendel-Hartvig I., Nelson B.D., Loof L., Totterman T.H. 1985. Primary biliary cirrhosis: further biochemical and immunological characterization of mitochondrial antigens. Clinical & Experimental Immunology 62: 371-379
11. Van de Water J., Gershwin M.E., Leung P., Ansari A., Coppel R.L. 1988. The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase. J. Exp. Med. 167: 1791-1799
12. Van de Water J., Fregeau D., Davis P., Ansari A., Danner D., Leung P., Coppel R., Gershwin M.E. 1988. Autoantibodies of primary biliary cirrhosis recognize dihydrolipoamide acetyltransferase and inhibit enzyme function. Journal of Immunology 141: 2321-2324
13. Coppel R.L., McNeilage L.J., Surh C.D., Van de Water J., Spithill T.W., Whittingham S., Gershwin M.E. 1988. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase. Proc. Natl. Acad. Sci. USA 85: 7317-7321
14. Yeaman S.J., Fussey S.P., Danner D.J., James O.F., Mutimer D.J., Bassendine M.F. 1988. Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens. Lancet 1: 1067-1070
15. Surh C.D., Danner D.J., Ahmed A., Coppel R.L., Mackay I.R., Dickson E.R., Gershwin M.E. 1989. Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain alpha-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen. Hepatology 9: 63-68
16. Iwayama T., Leung P.S., Coppel R.L., Roche T.E., Patel M.S., Mizushima Y., Nakagawa T., Dickson R., Gershwin M.E. 1991. Specific reactivity of recombinant human PDC-E1 alpha in primary biliary cirrhosis. J. Autoimmun. 4: 769-778
17. Fregeau D.R., Davis P.A., Danner D.J., Ansari A., Coppel R.L., Dickson E.R., Gershwin M.E. 1989. Antimitochondrial antibodies of primary biliary cirrhosis recognize dihydrolipoamide acyltransferase and inhibit enzyme function of the branched chain alpha-ketoacid dehydrogenase complex. J. Immunol. 142: 3815-3820
18. Fregeau D.R., Prindiville T., Coppel R.L., Kaplan M., Dickson E.R., Gershwin M.E. 1990. Inhibition of alpha-ketoglutarate dehydrogenase activity by a distinct population of autoantibodies recognizing dihydrolipoamide succinyltransferase in primary biliary cirrhosis. Hepatology 11: 975-981
19. Fregeau D.R., Roche T.E., Davis P.A., Coppel R., Gershwin M.E. 1990. Primary biliary cirrhosis. Inhibition of pyruvate dehydrogenase complex activity by autoantibodies specific for E1 alpha, a non-lipoic acid containing mitochondrial enzyme. J. Immunol. 144: 1671-1676
20. Fussey S.P., West S.M., Lindsay J.G., Ragan C.I., James O.F., Bassendine M.F., Yeaman S.J. 1991. Clarification of the identity of the major M2 autoantigen in primary biliary cirrhosis. Clin. Sci. 80: 451-455
21. Fussey S.P., Bassendine M.F., James O.F., Yeaman S.J. 1989. Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis. FEBS Lett. 246: 49-53
22. Gershwin M.E., Coppel R.L., Mackay I.R. 1988. Primary biliary cirrhosis and mitochondrial autoantigens - insights from molecular biology. (Review) Hepatology 8: 147-151
23. Gershwin M.E., Mackay I.R. 1991. Primary biliary cirrhosis: paradigm or paradox for autoimmunity. Gastroenterology 100: 822-833
24. Leung P.S., Van de Water J., Coppel R.L., Gershwin M.E. 1991. Molecular characterization of the mitochondrial autoantigens in primary biliary cirrhosis. Immunol. Res. 10: 518-527
25. Gershwin M.E., Rowley M., Davis P.A., Leung P., Coppel R., Mackay I.R. 1992. Molecular biology of the 2-oxo-acid dehydrogenase complexes and anti-mitochondrial antibodies. Prog. Liver Dis. 10: 47-61
26. Surh C.D., Coppel R., Gershwin M.E. 1990. Structural requirement for autoreactivity on human pyruvate dehydrogenase-E2, the major autoantigen of primary biliary cirrhosis. Implication for a conformation autoepitope. J. Immunol. 144: 3367-3374
27. Leung P.S.C., Chuang D.T., Wynn R.M., Cha S., Danner D.J., Ansari A., Coppel R., Gershwin M.E. 1995. Autoantibodies to BCOADC-E2 patients with primary biliary cirrhosis recognize a conformational epitope. Hepatology 22: 505-513
28. Cha S., Leung P.S., Gershwin M.E., Fletcher M.P., Ansari A.A., Coppel R.L. 1993. Combinatorial autoantibodies to dihydrolipoamide acetyltransferase, the major autoantigen of primary biliary cirrhosis. Proc. Natl. Acad. Sci. USA 90: 2527-2531
29. Moteki S., Leung P.S.C., Dickson E.R., Van Thiel D.H., Galperin C., Buch T., Alarcon-Segovia D., Kershenobich D., Kawano K., Coppel R.L., Matuda S., Gershwin M.E. Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex (OGDC-E2) in primary biliary cirrhosis using recombinant OGDC-E2. Hepatology (in press)
30. Baum H. 1995. Mitochondrial antigens, molecular mimicry and autoimmune disease. Biochimica et Biophysica Acta 1271: 111-121
31. Surh C.D., Cooper A.E., Coppel R.L., Leung P., Ahmed A., Dickson R., Gershwin M.E. 1988. The predominance of IgGS and IgM isotype antimitochondrial autoantibodies against recombinant fused mitochondrial polypeptide in patients with primary biliary cirrhosis. Hepatology 8: 290-295
32. Mendel-Hartvig, I., Frostell A., Totterman T.H. 1987. Primary biliary cirrhosis: antigenic specificity of IgM-type mitochondrial antibodies analyzed by immunoblotting and ELISA. International Archives of Allergy & Applied Immunology 83: 265-270
33. Mutimer D.J., Fussey S.P., Yeaman S.J., Kelly P.J. James O.F., Bassendine M.F. 1989. Frequency of IgG and IgM autoantibodies to four specific M2 mitochondrial autoantigens in primary biliary cirrhosis. Hepatology 10: 403-407
34. Mackay I.R. 1958. Primary biliary cirrhosis showing high titer of autoantibody: report of a case. N. Engl. J. Med. 254: 185.
35. Gershwin M.E., Mackay I.R., Sturgess A., Coppel R.L. 1987. Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J. Immunol. 138: 3525-3531
36. Surh C.D., Roche T.E., Danner D.J., Ansari A., Coppel R.L., Prindiville T., Dickson E.R., Gershwin M.E. 1989. Antimitochondrial autoantibodies in primary biliary cirrhosis recognize cross-reactive epitope(s) on protein X and dihydrolipoamide acetyltransferase of pyruvate dehydrogenase complex. Hepatology 10: 127-133
37. Tartakovsky F., Worman H.J. 1995. Detection of Gp210 autoantibodies in primary biliary cirrhosis using a recombinant protein containing the predominant autoepitope. Hepatology 21: 495-500
38. Mackay I.R., Gershwin M.E. 1989. Primary biliary cirrhosis: current knowledge, perspectives, and future directions. Semin. Liv. Dis. 9: 149-157
39. Patel M.S., Roche T.E. 1990. Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4: 3224-3233
40. Perham R.N., Packman L.C. 1989. 2-Oxo acid dehydrogenase multienzyme complexes: domains, dynamics, and design. Ann. N.Y. Acad. Sci. 573: 1-20
41. Fussey S.P., Lindsay J.G., Fuller C., Perham R.N., Dale S., James O.F., Bassendine M.F., Yeaman S.J. 1991. Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes. Hepatology 13: 467-474
42. Fussey S.P., Ali S.T., Guest J.R., James O.F., Bassendine M.F., Yeaman S.J. 1990. Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region. Proc. Natl. Acad. Sci. USA 87: 3987-3991
43. Leung P.S., Iwayama T., Coppel R.L., Gershwin M.E. 1990. Site-directed mutagenesis of lysine within the immunodominant autoepitope of PDC-E2. Hepatology 12: 1321-1328
44. Quinn J., Diamond A.G., Palmer J.M., Bassendine M.F., James O.F., Yeaman S.J. 1993. Lipoylated and unlipoylated domains of human PDC-E2 as autoantigens in primary biliary cirrhosis: significance of lipoate attachment. Hepatology 18: 1384-1391
45. Tuaillon N., Andre C., Briand J.P., Penner E., Muller S. 1992. A lipoyl synthetic octadecapeptide of dihydrolipoamide acetyltransferase specifically recognized by anti-M2 autoantibodies in primary biliary cirrhosis. J. Immunol. 148: 445-450
46. Van de Water J., Turchany J., Leung P.S., Lake J., Munoz S., Surh C.D., Coppel R., Ansari A., Nakanuma Y., Gershwin M.E. 1993. Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2. J. Clin. Invest. 91: 2653-2664
47. Tsuneyama K., Van de Water J., Nakanuma Y., Cha S., Ansari A., Coppel R., Gershwin M.E. 1994. Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC-E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sjogren's syndrome. Hepatology 20: 893-898
48. Nakanuma Y., Tsuneyama K., Kono N., Hoso M., Van de Water J., Gershwin M.E. 1995. Biliary epithelial expression of pyruvate dehydrogenase complex in primary biliary cirrhosis: an immunohistochemical and immunoelectron microscopic study. Hum. Pathol. 26: 92-98
49. Cha S., Leung P.S., Coppel R.L., Van de Water J., Ansari A.A., Gershwin M.E. 1994. Heterogeneity of combinatorial human autoantibodies against PDC-E2 and biliary epithelial cells in patients with primary biliary cirrhosis. Hepatology 20: 574-583
50. Coppel R.L., Gershwin M.E. 1995. Primary biliary cirrhosis: The molecule and the mimic. Immunol. Rev. 144: 17-49
51. Joplin R., Lindsay J.G., Hubscher S.G., Johnson G.D., Shaw J.C., Strain A.J., Neuberger J.M. 1991. Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study. Hepatology 14: 442-447
52. Joplin R., Lindsay J.G., Johnson G.D., Strain A., Neuberger J. 1992. Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial cells in PBC. Lancet 339: 93-94
53. Joplin R.E., Johnson G.D., Matthews J.B., Hamburger J., Lindsay J.G., Hubscher S.G., Strain A.J., Neuberger J.M. 1994. Distribution of pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2) and another mitochondrial marker in salivary gland and biliary epithelium from patients with primary biliary cirrhosis. Hepatology 19: 1375-1380
54. Moebius U., Manns M., Hess G., Kober G., Meyer zum Buschenfelde K.H., Meuer S.C. 1990. T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): oligoclonality of PBC-derived T cell clones. Eur. J. Immunol. 20: 889-896
55. Lohr H., Fleischer B., Gerken G., Yeaman S.J., Meyer zum Buschenfelde K.H., Manns M. 1993. Autoreactive liver-infiltrating T cells in primary biliary cirrhosis recognize inner mitochondrial epitopes and the pyruvate dehydrogenase complex. J. Hepatol. 18: 322-327
56. Meuer S.C., Moebius U., Manns M.M., Dienes H.P., Ramadori G., Hess G., Hercend T., Meyer zum Buschenfelde K.H. 1988. Clonal analysis of human T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis. European Journal of Immunology 18: 1447-1452
57. Krams S.M., Van de Water J., Coppel R.L., Esquivel C., Roberts J., Ansari A., Gershwin M.E. 1990. Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis. Hepatology 12: 306-313
58. Van de Water J., Ansari A.A., Surh C.D., Coppel R., Roche T., Bonkovsky H., Kaplan M., Gershwin M.E. 1991. Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis. J. Immunol. 146: 89-94
59. Van den Oord J.J., Fevery J., de Groote J., Desmet V.J. 1984. Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis. Liver 4: 264-274
60. Van den Oord J.J., Sciot R., Desmet V.J. 1987. Expression of MHC products by normal and abnormal bile duct epithelium. J. Hepatology 3: 310-317
61. Spengler U., Pape G.R., Hoffmann R.M., Johnson J.P., Eisenburg J., Paumgartner G., Riethmuller G. 1988. Differential expression of MHC class II subregion products on bile duct epithelial cells and hepatocytes in patients with primary biliary cirrhosis. Hepatology 8: 459-462
62. Yasoshima M., Nakanuma Y., Tsuneyama K., Van de Water J., Gershwin M.E. 1995. Immunohistochemical analysis of adhesion molecules in the micro-environment of portal tracts in relation to aberrant expression of PDC-E2 and HLA-DR on the bile ducts in primary biliary cirrhosis. J. Pathol. 175: 319-325
63. A.G. L., Jazrawi R.P., J.H. L., M. Z., Douds A.C., Maxwell J.D., Northfield T.C. 1995. Soluble S-selectin and vascular cell adhesion molecule (VCAM-1) in primary biliary cirrhosis. J. Hepatology 22: 416-422
64. Van de Water J., Ansari A., Prindiville T., Coppel R., Ricalton N., Kotzin B.L., Liu S., Roche T.E., Krams S.M., Munoz S., Gershwin M.E. 1995. Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis. J. Exp. Med. 181: 723-733
65. Jones D.E.J., Palmer J.M., James O.F.W., Yeaman S.J., Bassendine M.F., Diamond A.G. 1995. T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis. Hepatology 21: 995-1002
66. Shimoda S., Nakamura M., Ishibashi H., Hayashida K., Niho Y. 1995. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. J. Exp. Med. 181: 1835-1845
67. Burroughs A.K., Rosenstein I.J., Epstein O., Hamilton-Miller J.M., Brumfitt W., Sherlock S. 1984. Bacteriuria and primary biliary cirrhosis. Gut 25: 133-137
68. Chohan M.R. 1973. Primary biliary cirrhosis in twin sisters. Gut 14: 213-214
69. Galbraith R.M., Smith M., Mackenzie R.M., Tee D.E., Doniach D., Williams R. 1974. High prevalence of seroimmunologic abnormalities in relatives of patients with active chronic hepatitis or primary biliary cirrhosis. N. Engl. J. Med. 290: 63-69
70. Jaup B.H., Zettergren L.S. 1980. Familial occurrence of primary biliary cirrhosis associated with hypergammaglobulinemia in descendants: a family study. Gastroenterology 78: 549-555
71. Iwayama T., Leung P.S., Rowley M., Munoz S., Nishioka M., Nakagawa T., Dickson E.R., Coppel R.L., Mackay I.R., Gershwin M.E. 1992. Comparative immunoreactive profiles of Japanese and American patients with primary biliary cirrhosis against mitochondrial autoantigens. International Archives of Allergy & Immunology 99: 28-33
72. Mella J.G., Roschmann E., Maier K.P., Volk B.A. 1995. Association of primary biliary cirrhosis with the allele HLA-DPB*0301 in a German population. Hepatology 21: 398-402
73. Begovich A.B., Klitz W., Moonsamy P.V., Van de Water J., Peltz G., Gershwin M.E. 1994. Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis. Tissue Antigens 43: 71-77
74. Leung P.S.C., Gershwin M.E. 1993. Immunoglobulin genes in autoimmunity. Int. Arch. Allergy Immunol. 101: 113-118
75. Begovich A.B., Bugawan T.L., Nepon B.S., Klitz W., Nepon G.T., Erlich H.A. 1989. A specific Dp-b allele is associated with pauciarticular juvenile rheumatoid arthritis but not with adult rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 186: 9489-9493
76. Dong R.P., Kimura A., Okubo R., Shinagawa H., Tamai H., Nishimura Y., Sazasuki T. 1992. HLA-DPB1 confer susceptibility to Grave's disease. Human Pathology 35: 165-172
77. Bassendine M.F., Dewar P.J., James O.F. 1985. HLA-DR antigens in primary biliary cirrhosis: lack of association. Gut 26: 625-628
78. Miyamori H., Kato Y., Kobayashi K., Hattori N. 1983. HLA antigens in Japanese patients with primary biliary cirrhosis and autoimmune hepatitis. Digestion 26: 213-217
79. Ercilla G., Pares A., Arriaga F. 1979. Primary biliary cirrhosis associated with HLA-DRw3. Tissue Antigens 14: 449-452
80. Gores G.J., Moore B., Fisher L.D., Powell F.C., Dickson E.R. 1987. Primary biliary cirrhosis: associations with class II major histocompatibility complex antigens. Hepatology 7: 889-892
81. Underhill J.A., Donaldson P.T., Doherty D.G., Manabe K., Williams R. 1995. HLA DPB polymorphism in primary sclerosing cholangitis and primary biliary cirrhosis. Hepatology 21: 959-962
82. Seki T., Kiyosawa K., Ota M., Furuta S., Fukushima H., Tanaka E., Yoshizawa K., Kumagai T., Mizuki N., Ando A., et al. 1993. Association of primary biliary cirrhosis with human leukocyte antigen DPB1*0501 in Japanese patients. Hepatology 18: 73-78
83. Underhill J., Donaldson P., Bray G., Doherty D., Portmann B., Williams R. 1992. Susceptibility to primary biliary cirrhosis is associated with the HLA-DR8-DQB1*0402 haplotype. Hepatology 16: 1414-1408
84. Manns M.P., Bremm A., Schneider P.M., Notghi A., Gerken G., Prager-Eberle M., Stradmann-Bellinghausen B., Meyer zum Buschenfelde K.H., Rittner C. 1991. HLA DRw8 and complement C4 deficiency as risk factors in primary biliary cirrhosis. Gastroenterology 101: 1367-1373
85. Onishi S., Sakamaki T., Maeda T., Iwamura S., Tomita A., Saibara T., Yamamoto Y. 1994. DNA typing of HLA class II genes; DRB1*0803 increases the susceptibility of Japanese to primary biliary cirrhosis. J. Hepatol. 21: 1053-1060
86. Morling N., Dalhoff K., Fugger L., Georgsen J., Jakobsen B., Ranek L., Odum N., Svejgaard A. 1992. DNA polymorphism of HLA class II genes in primary biliary cirrhosis. Immunogenetics 35: 112-116
87. Zhang L., Weetman A.P., Bassendine M., Oliveira D.B. 1994. Major histocompatibility complex class-II alleles in primary biliary cirrhosis. Scand. J. Immunol. 39: 104-106
88. Tsuneyama K., Van de Water J., Leung P.S.C., Cha S., Nakanuma Y., Kaplan M., De Lellis R., Coppel R., Ansari A., Gershwin M.E. 1995. Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression. Hepatology 21: 1031-1037
89. Nakanuma Y., Kono N. 1991. Expression of HLA-DR antigens on interlobular bile ducts in primary biliary cirrhosis and other hepatobiliary diseases: an immunohistochemical study. Hum. Pathol. 22: 431-436
90. Leung P.S., Krams S., Munoz S., Surh C.P., Ansari A., Kenny T., Robbins D.L., Fung J., Starzl T.E., Maddrey W., Coppel R.L., Gershwin M.E. 1992. Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis. J. Autoimmun. 5: 703-718
91. Polack M., Raubitschek A.A., Larrick J.W. 1987. Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of liposaccharides. J. Clin. Invest. 79: 1421-1438
92. Huse W.D., Sastry L., Iverson S.A., Kang A.S., Atling-Mees M., Burton D.R., Benkovic S.J., Lerner R.A. 1989. Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science 246: 1275-1281
93. Pascual V., Cha S., Gershwin M.E., Capra J.D., Leung P.S. 1994. Nucleotide sequence analysis of natural and combinatorial anti-PDC-E2 antibodies in patients with primary biliary cirrhosis. Recapitulating immune selection with molecular biology. J. Immunol. 152: 2577-2585
94. Pascual V., Verkruyse L., Casey M.L., Capra J.D. 1993. Analysis of immunoglobulin heavy chain gene segment utilization in human fetal liver: revisiting the proximal utilization hypothesis. J. Immunol. 151: 4164-4172
95. Berman J.E., Mellis S., Pollock J.R., Smith C.L., Suh H., Heinke B., Kowal C., Surti U., Chess L., Alt F.W. 1988. Content and organization of the human Ig VH locus: definition of three new families and linkage to the Ig CH locus. EMBO 7: 727-738
96. Cairns E., Kwong P.C., Misener V., Ip P., Bell D.A., Siminovitch K.A. 1989. Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. J. Immunol. 143: 685-691
97. Pascual V., Victor K., Randen I., Thompson K.M., Fu S.M., Forre O., Natvig J.B., Capra J.D. 1992. Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR3. Scand. J. Immunol. 36: 349-362
98. Tomlinson I.M., Walter G., Marks J.D., Llewelyn M.B., Winter G. 192. The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops. J. Mol. Biol. 227: 776-798
99. Humphries C.G., Shen A., Kuziel W.A., Capra J.D., Blattner F.R., Tucker P.W. 1988. A new human immunoglobulin Vh family preferentially rearranged in premature B-cell tumors (letters). Nature 331: 446
100. Mathyssens G., Rabbits H. 1980. Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc. Natl. Acad. Sci. USA 77: 6561-6570
101. Lee K.H., Matsuda F., Kinashi T., Kodaira M., Honjo T. 1987. A novel family of variable genes of the human immunoglobulin heavy chain. J. Mol. Biol. 195: 761-768
102. Chuchana P., Blancher A., Brockly F., Alexandre D., Lefranc G., Lefranc M.P 1990. Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups. Eur. J. Immunol. 20: 1317-1325
103. Fukishima N., Nakamura M., Matsui M., Ikematsu H., Koike K., Ishibashi H., Hayashida K., Niho Y. 1995. Establishment and structural analysis of human mAb to the E2 component of the 2-oxoglutarate dehydrogenase complex generated from a patient with primary biliary cirrhosis. Int. Immunol. 7: 1047-1055