title: Amplification of autoimmune disease by infection.
abstract: Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even relapse. The evidence suggests that the organisms are specifically imported to the inflammatory sites and cause further tissue destruction, especially when the host is immunosuppressed. We review the evidence for the amplification of autoimmune inflammatory disease by microbial infection, which may be a general mechanism applicable to many human diseases. We suggest that patients with autoimmune disorders receiving immunosuppressing drugs should benefit from preventive antiviral therapy.
authors.affiliation: Immunology Program, Graduate School of Medical Sciences, Weill Medical College, Cornell University, Ithaca, NY, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Posnett
authors.forename: Dmitry
authors.initials: D
authors.lastname: Yarilin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology; D001692:Biological Transport; D002690:Chlamydia Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D023521:Chlamydophila Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology; D006566:Herpesviridae Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007249:Inflammation; D051379:Mice; D018448:Models, Immunological; D009928:Organ Specificity; D010322:Parvoviridae Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D016732:Parvovirus B19, Human; D018144:Rhadinovirus; D014412:Tumor Virus Infections / Q000150:complications / Q000276:immunology; D014766:Viremia / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology / Q000517:prevention & control; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents
references.citation: J Med Virol. 1997 Nov;53(3):229-32
references.pmid: 9365887
references.citation: Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):928-37
references.pmid: 9517614
references.citation: Eur J Immunol. 1998 Mar;28(3):936-48
references.pmid: 9541589
references.citation: J Clin Invest. 2003 Jun;111(11):1757-69
references.pmid: 12782678
references.citation: Eur J Immunol. 2003 Jul;33(7):1849-58
references.pmid: 12811845
references.citation: Arch Pathol Lab Med. 2003 Jul;127(7):840-4
references.pmid: 12823038
references.citation: Trends Microbiol. 2003 Jul;11(7):293-5
references.pmid: 12875809
references.citation: Nature. 2003 Jul 24;424(6947):456-61
references.pmid: 12879076
references.citation: Immunol Lett. 2003 Aug 5;88(2):109-12
references.pmid: 12880679
references.citation: J Am Coll Cardiol. 2003 Aug 6;42(3):466-72
references.pmid: 12906974
references.citation: J Clin Virol. 2003 Oct;28(2):165-8
references.pmid: 12957186
references.citation: Curr Opin Rheumatol. 2003 Sep;15(5):528-34
references.pmid: 12960476
references.citation: Immunol Cell Biol. 2003 Oct;81(5):350-3
references.pmid: 12969322
references.citation: Biol Blood Marrow Transplant. 2003 Sep;9(9):543-58
references.pmid: 14506657
references.citation: J Cutan Pathol. 2004 Jan;31(1):43-50
references.pmid: 14675284
references.citation: Cell Microbiol. 2004 Feb;6(2):117-27
references.pmid: 14706098
references.citation: J Immunol. 2004 Jan 15;172(2):1287-94
references.pmid: 14707107
references.citation: J Immunol. 2004 Feb 1;172(3):1935-44
references.pmid: 14734779
references.citation: N Engl J Med. 2004 Feb 5;350(6):586-97
references.pmid: 14762186
references.citation: Mod Pathol. 2004 Jul;17(7):781-9
references.pmid: 15044921
references.citation: Curr Opin Rheumatol. 2004 Jul;16(4):399-405
references.pmid: 15201603
references.citation: Curr Opin Infect Dis. 2004 Aug;17(4):357-61
references.pmid: 15241082
references.citation: J Immunol. 2004 Oct 1;173(7):4675-83
references.pmid: 15383603
references.citation: J Immunol. 2004 Oct 15;173(8):5238-46
references.pmid: 15470069
references.citation: Leuk Lymphoma. 2002 Mar;43(3):517-22
references.pmid: 12002754
references.citation: Blood. 2002 Jun 1;99(11):3909-15
references.pmid: 12010788
references.citation: Curr Opin Immunol. 2002 Aug;14(4):444-51
references.pmid: 12088678
references.citation: J Med Virol. 2002 Jul;67(3):364-9
references.pmid: 12116029
references.citation: J Rheumatol. 1989 May;16(5):677-80
references.pmid: 2547061
references.citation: Lancet. 1990 May 5;335(8697):1047-50
references.pmid: 1970369
references.citation: Lancet. 1990 Sep 8;336(8715):590-3
references.pmid: 1697399
references.citation: Rev Infect Dis. 1990 Sep-Oct;12 Suppl 7:S701-10
references.pmid: 2173099
references.citation: Clin Exp Rheumatol. 1990 Jul-Aug;8 Suppl 5:41-4
references.pmid: 2245525
references.citation: J Pathol. 1991 Apr;163(4):351-60
references.pmid: 1851828
references.citation: J Gen Virol. 1991 Jun;72 ( Pt 6):1401-8
references.pmid: 1646280
references.citation: Nephrol Dial Transplant. 1990;5(12):1045-50
references.pmid: 1965736
references.citation: Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 1):112-8
references.pmid: 1728974
references.citation: Mod Pathol. 1992 May;5(3):292-302
references.pmid: 1323104
references.citation: Eur J Clin Microbiol Infect Dis. 1992 Jun;11(6):564-6
references.pmid: 1326434
references.citation: Rheumatol Int. 1992;12(4):147-51
references.pmid: 1439481
references.citation: J Infect Dis. 1993 Mar;167(3):744-8
references.pmid: 8440942
references.citation: Am J Obstet Gynecol. 1993 May;168(5):1457-62
references.pmid: 8498427
references.citation: Doc Ophthalmol. 1992;82(3):217-21
references.pmid: 1303857
references.citation: J Exp Med. 1994 Apr 1;179(4):1173-84
references.pmid: 8145036
references.citation: Br J Rheumatol. 1994 Apr;33(4):317-22
references.pmid: 8156301
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3872-6
references.pmid: 7909607
references.citation: J Immunol. 1994 Sep 1;153(5):2268-77
references.pmid: 7519647
references.citation: J Clin Invest. 1994 Dec;94(6):2525-31
references.pmid: 7989613
references.citation: N Engl J Med. 1995 Jan 5;332(1):12-8
references.pmid: 7990860
references.citation: Mayo Clin Proc. 1995 Mar;70(3):261-5
references.pmid: 7861814
references.citation: Bone Marrow Transplant. 1995 Apr;15(4):557-61
references.pmid: 7655381
references.citation: Hum Reprod. 1995 May;10(5):1070-4
references.pmid: 7657743
references.citation: J Med Virol. 1995 Apr;45(4):462-8
references.pmid: 7666047
references.citation: Br J Rheumatol. 1995 Sep;34(9):809-13
references.pmid: 7582718
references.citation: J Exp Med. 1995 Nov 1;182(5):1213-21
references.pmid: 7595192
references.citation: J Virol. 1996 May;70(5):3286-9
references.pmid: 8627812
references.citation: Eur Heart J. 1995 Dec;16 Suppl O:46-9
references.pmid: 8682100
references.citation: Antiviral Res. 1996 Jun;31(1-2):1-21
references.pmid: 8793005
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11137-42
references.pmid: 8855322
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11143-8
references.pmid: 8855323
references.citation: J Clin Microbiol. 1996 Sep;34(9):2320-1
references.pmid: 8862611
references.citation: Bone Marrow Transplant. 1996 Aug;18(2):339-45
references.pmid: 8864444
references.citation: J Immunol. 1996 Nov 15;157(10):4697-706
references.pmid: 8906851
references.citation: J Exp Med. 1996 Nov 1;184(5):1791-800
references.pmid: 8920867
references.citation: Cell. 1996 Nov 29;87(5):811-22
references.pmid: 8945509
references.citation: Br J Rheumatol. 1996 Nov;35(11):1075-81
references.pmid: 8948292
references.citation: Ann Rheum Dis. 1996 Dec;55(12):895-900
references.pmid: 9014583
references.citation: Eur J Clin Microbiol Infect Dis. 1996 Dec;15(12):954-7
references.pmid: 9031882
references.citation: J Virol. 1997 Mar;71(3):2478-81
references.pmid: 9032386
references.citation: Semin Diagn Pathol. 1997 Feb;14(1):27-34
references.pmid: 9044507
references.citation: Microb Pathog. 1997 Mar;22(3):133-42
references.pmid: 9075216
references.citation: Lancet. 1997 Apr 12;349(9058):1063-5
references.pmid: 9107245
references.citation: J Virol. 1997 Jun;71(6):4571-80
references.pmid: 9151851
references.citation: J Clin Microbiol. 1997 Jun;35(6):1600-3
references.pmid: 9163493
references.citation: Infect Immun. 1997 Jun;65(6):2067-73
references.pmid: 9169733
references.citation: Infect Immun. 1997 Jun;65(6):2145-52
references.pmid: 9169744
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7600-5
references.pmid: 9207138
references.citation: J Virol. 1997 Oct;71(10):7963-8
references.pmid: 9311888
references.citation: J Clin Invest. 2003 Jun;111(11):1647-9
references.pmid: 12782667
references.citation: Rheum Dis Clin North Am. 1998 May;24(2):261-73
references.pmid: 9606758
references.citation: Nat Med. 1998 Jul;4(7):781-5
references.pmid: 9662368
references.citation: Clin Infect Dis. 1998 Jul;27(1):137-41
references.pmid: 9675467
references.citation: J Biol Chem. 1998 Sep 4;273(36):23367-75
references.pmid: 9722571
references.citation: Eur J Immunol. 1999 Mar;29(3):973-85
references.pmid: 10092102
references.citation: J Immunol. 1999 Mar 15;162(6):3694-701
references.pmid: 10092832
references.citation: Immunology. 1999 Feb;96(2):272-7
references.pmid: 10233705
references.citation: J Virol. 1999 Jun;73(6):4806-12
references.pmid: 10233941
references.citation: Blood. 1999 Jun 15;93(12):4044-58
references.pmid: 10361101
references.citation: Ann Neurol. 1999 Jul;46(1):6-14
references.pmid: 10401775
references.citation: Arthritis Rheum. 1999 Jul;42(7):1485-96
references.pmid: 10403278
references.citation: Br J Dermatol. 1999 Jul;141(1):94-102
references.pmid: 10417521
references.citation: J Clin Invest. 1999 Sep;104(5):527-9
references.pmid: 10487765
references.citation: Drugs. 2004;64(24):2763-92
references.pmid: 15563248
references.citation: Am Heart J. 1999 Nov;138(5 Pt 2):S465-8
references.pmid: 10539849
references.citation: BJU Int. 1999 Dec;84(9):976-81
references.pmid: 10571623
references.citation: Rev Med Virol. 1999 Oct-Dec;9(4):245-62
references.pmid: 10578120
references.citation: Ocul Immunol Inflamm. 1999 Dec;7(3-4):215-21
references.pmid: 10611730
references.citation: Cell. 1999 Dec 23;99(7):817-27
references.pmid: 10619434
references.citation: J Neuroimmunol. 1999 Dec;100(1-2):74-97
references.pmid: 10695718
references.citation: Am J Kidney Dis. 2000 Jun;35(6):1166-74
references.pmid: 10845832
references.citation: Arthritis Rheum. 2000 Jun;43(6):1218-25
references.pmid: 10857780
references.citation: J Neurovirol. 2000 May;6 Suppl 2:S85-7
references.pmid: 10871792
references.citation: Microb Pathog. 2000 Jul;29(1):17-24
references.pmid: 10873487
references.citation: Blood. 2000 Jul 1;96(1):126-31
references.pmid: 10891440
references.citation: Arthritis Rheum. 2000 Jul;43(7):1543-51
references.pmid: 10902759
references.citation: Expert Rev Anti Infect Ther. 2003 Oct;1(3):493-503
references.pmid: 15482145
references.citation: Nature. 1971 May 7;231(5297):47-9
references.pmid: 4325100
references.citation: Infect Immun. 1973 Apr;7(4):620-4
references.pmid: 4357604
references.citation: Lancet. 1975 Jan 11;1(7898):72-3
references.pmid: 46024
references.citation: Trans R Soc Trop Med Hyg. 1982;76(3):311-3
references.pmid: 6287684
references.citation: Acta Pathol Jpn. 1984 Jul;34(4):869-74
references.pmid: 6091403
references.citation: Cell. 1997 Oct 3;91(1):119-26
references.pmid: 9335340
references.citation: J Clin Invest. 1997 Oct 15;100(8):1969-79
references.pmid: 9329960
references.citation: Histopathology. 1997 Sep;31(3):237-51
references.pmid: 9354894
references.citation: Nat Rev Immunol. 2001 Oct;1(1):75-82
references.pmid: 11905817
references.citation: Clin Nephrol. 2002 Mar;57(3):246-50
references.pmid: 11924757
references.citation: Pathol Int. 2002 Jan;52(1):31-9
references.pmid: 11940204
references.citation: Rheumatology (Oxford). 2002 Apr;41(4):445-9
references.pmid: 11961176
references.citation: Pediatr Hematol Oncol. 2002 Sep;19(6):433-7
references.pmid: 12186367
references.citation: Scand J Immunol. 1998 Sep;48(3):293-9
references.pmid: 9743216
references.citation: Transpl Int. 1998;11(5):336-44
references.pmid: 9787409
references.citation: Virchows Arch. 1998 Oct;433(4):341-8
references.pmid: 9808436
references.citation: Am J Kidney Dis. 1998 Nov;32(5):785-93
references.pmid: 9820448
references.citation: J Virol. 1999 Jan;73(1):754-9
references.pmid: 9847383
references.citation: Circulation. 2000 Aug 15;102(7):779-85
references.pmid: 10942747
references.citation: J Immunol. 2000 Sep 15;165(6):2975-81
references.pmid: 10975805
references.citation: N Engl J Med. 2000 Nov 9;343(19):1369-77
references.pmid: 11070101
references.citation: Pediatr Int. 2000 Dec;42(6):708-10
references.pmid: 11192536
references.citation: Arthritis Res. 2000;2(2):154-64
references.pmid: 11062606
references.citation: Arthritis Res. 2000;2(3):236-43
references.pmid: 11056669
references.citation: Arthritis Res. 2000;2(4):249-51
references.pmid: 11094435
references.citation: Arthritis Res. 2000;2(6):429-32
references.pmid: 11094453
references.citation: Rev Med Virol. 2001 Jan-Feb;11(1):23-36
references.pmid: 11241800
references.citation: Neurology. 2001 Mar 27;56(6):758-65
references.pmid: 11274311
references.citation: Lupus. 2001;10(4):249-52
references.pmid: 11341100
references.citation: Arthritis Rheum. 2001 May;44(5):1122-6
references.pmid: 11352244
references.citation: Ann Neurol. 2001 May;49(5):585-9
references.pmid: 11357948
references.citation: Transpl Infect Dis. 2001 Jun;3(2):88-96
references.pmid: 11395974
references.citation: J Virol. 2001 Aug;75(16):7517-27
references.pmid: 11462024
references.citation: Nat Immunol. 2001 Sep;2(9):797-801
references.pmid: 11526389
references.citation: J Virol. 2001 Oct;75(20):9966-76
references.pmid: 11559829
references.citation: Viral Immunol. 2001;14(3):227-50
references.pmid: 11572634
references.citation: Arthritis Rheum. 2001 Sep;44(9):2038-45
references.pmid: 11592365
references.citation: Immunity. 2001 Dec;15(6):997-1009
references.pmid: 11754820
references.citation: J Clin Invest. 2002 Jan;109(1):79-87
references.pmid: 11781353
references.citation: Herpes. 2001 Nov;8(3):60-3
references.pmid: 11867021
references.citation: Arthritis Res. 2002;4(1):5-9
references.pmid: 11879531
references.citation: Mod Pathol. 2002 Jul;15(7):759-64
references.pmid: 12118114
references.citation: Curr Opin Microbiol. 2002 Aug;5(4):403-7
references.pmid: 12160860
references.citation: Adv Virus Res. 1987;33:91-174
references.pmid: 3296697
references.citation: Lancet. 1988 Jan 2-9;1(8575-6):11-4
references.pmid: 2891887
references.citation: Clin Microbiol Rev. 1989 Apr;2(2):204-16
references.pmid: 2539899
references.citation: Mod Pathol. 2002 Sep;15(9):914-22
references.pmid: 12218208
references.citation: Curr Top Microbiol Immunol. 2002;269:235-56
references.pmid: 12224512
references.citation: J Rheumatol. 2002 Sep;29(9):1827-35
references.pmid: 12233874
references.citation: J Infect Dis. 2002 Oct 15;186 Suppl 1:S99-S109
references.pmid: 12353194
references.citation: J Infect Dis. 2002 Oct 15;186 Suppl 1:S131-7
references.pmid: 12353198
references.citation: J Clin Virol. 2002 Aug;25 Suppl 2:S23-36
references.pmid: 12361754
references.citation: J Clin Virol. 2002 Aug;25 Suppl 2:S57-61
references.pmid: 12361757
references.citation: J Clin Virol. 2002 Aug;25 Suppl 2:S123-36
references.pmid: 12361763
references.citation: J Invest Dermatol. 2002 Oct;119(4):793-7
references.pmid: 12406322
references.citation: Curr Opin Rheumatol. 2002 Nov;14(6):694-8
references.pmid: 12410093
references.citation: Immunity. 2002 Nov;17(5):653-64
references.pmid: 12433371
references.citation: J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):739-46
references.pmid: 12438480
references.citation: Clin Rheumatol. 2002 Nov;21(6):505-10
references.pmid: 12447636
references.citation: J Rheumatol. 2002 Dec;29(12):2513-20
references.pmid: 12465144
references.citation: J Exp Med. 2002 Dec 16;196(12):1639-44
references.pmid: 12486106
references.citation: Urology. 2002 Dec;60(6 Suppl):8-12; discussion 13
references.pmid: 12521579
references.citation: Diabetes Metab Res Rev. 2003 Jan-Feb;19(1):8-31
references.pmid: 12592641
references.citation: Nat Med. 2003 Mar;9(3):307-14
references.pmid: 12592401
references.citation: Bone Marrow Transplant. 2003 Feb;31(3):145-55
references.pmid: 12621474
references.citation: J Neuroimmunol. 2003 Mar;136(1-2):1-8
references.pmid: 12620637
references.citation: Semin Arthritis Rheum. 2003 Apr;32(5):326-33
references.pmid: 12701043
references.citation: Arthritis Rheum. 2003 May;48(5):1223-8
references.pmid: 12746895
references.citation: Int Arch Allergy Immunol. 1995 Mar;106(3):235-40
references.pmid: 7888786
references.citation: Lancet. 1995 Apr 29;345(8957):1118
references.pmid: 7715366
references.citation: J Med Virol. 1995 Jun;46(2):103-8
references.pmid: 7636495
references.citation: Lancet. 1995 Aug 19;346(8973):475-6
references.pmid: 7637482