Recent Findings Shed Light on the Aetiopathogenesis of Sjögren’s Syndrome

Zusammenfassung

Das systemische klinische Bild der Patienten mit SS kann auf eine Disposition vieler Zellarten zurückgeführt werden, bei einer Konfrontation mit Stressreizen überzureagieren. Dies beeinflusst die elementaren zellulären Vorgänge wie Apoptose und Acethylcholine-Rezeptor-Signalvermittlung. Diese Hyperreaktivität des Gewebes kann auch die beobachteten autoimmunogenen Eigenschaften erklären und könnte eine ätiopathogenetische Determinante beim SS darstellen.

Abstract

The systemic clinical picture of SS patients can be traced back to a disposition of many cell types to over-react when confronted with stress stimuli. This will influence basic cellular processes such as apoptosis and acetylcholine receptor signaling. This tissue hyper-reactivity may also explain the observed autoimmune features, and may constitute a major aetiopathogenetic determinant in SS.

Schlüsselwörter

Sjögren-Syndrom - Stressreaktion - Antigen präsentierende Zellen - Acetylcholin

Key words

Sjögren’s syndrome - stress response - antigen-presenting cells - acetylcholine

Reference

• 1 Fox R I, Fong S, Chen P P. et al . Autoantibody production in Sjogren’s syndrome: a hypothesis regarding defects in somatic diversification of germ line encoded genes.  In Vivo. 1988;  2 47-55
• 2 Smith G C, Jackson S P. The DNA-dependent protein kinase.  Genes Dev. 1999;  13 916-934
• 3 Tan E M. Interactions between autoimmunity and molecular and cell biology. Bridges between clinical and basic sciences.  J Clin Invest. 1989;  84 1-6
• 4 Suwa A, Hirakata M, Takeda Y. et al . Autoantibodies to DNA-dependent protein kinase. Probes for the catalytic subunit.  J Clin Invest. 1996;  97 1417-1421
• 5 Henriksson G, Brant M, Sallmyr A. et al . Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjogren’s syndrome cells.  Eur J Clin Invest. 2002;  32 458-465
• 6 Henriksson G, Sallmyr A, Du L. et al . Enhanced DNA-dependent protein kinase activity in Sjogren’s syndrome B cells.  Rheumatol. 2004;  43 1109-1115
• 7 Jackson S P. Sensing and repairing DNA double-strand breaks.  Carcinogenesis. 2002;  23 687-696
• 8 Henriksson G, Brant M, Sandor Z. et al . Sjogren’s syndrome: lymphoma predisposition coupled with a reduced frequency of t(14;18) translocations in blood lymphocytes.  Mol Carcinog. 1999;  24 226-231
• 9 Seidman M M, Bredberg A, Seetharam S. et al . Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.  Proc Natl Acad Sci USA. 1987;  84 4944-4948
• 10 Henriksson G, Sandor Z, Aponyi I. et al . A reduced level of multiple mutation in a shuttle vector passaged in Sjogren’s syndrome cells.  Mutat Res. 1994;  324 103-110
• 11 Lavasani S, Henriksson G, Brant M. et al . Abnormal DNA damage-inducible protein in cells from Sjögren’s syndrome patients.  J Autoimmun. 1998;  11 363-369
• 12 Guo K, Major G, Foster H. et al . Defective repair of O6-methylguanine-DNA in primary Sjogren’s syndrome patients predisposed to lymphoma.  Ann Rheum Dis. 1995;  54 229-232
• 13 Harris G, Asbery L, Lawley P D. et al . Defective repair of 0(6)-methylguanine in autoimmune diseases.  Lancet. 1982;  2 952-956
• 14 Zeher M, Szodoray P, Gyimesi E. et al . Correlation of increased susceptibility to apoptosis of CD4 + T cells with lymphocyte activation and activity of disease in patients with primary Sjogren’s syndrome.  Arthritis Rheum. 1999;  42 1673-1681
• 15 Larsson A, Henriksson G, Manthorpe R. et al . Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren’s syndrome subjects: lack of correlation with apoptosis.  Scand J Immunol. 2001;  54 328-334
• 16 Choi E K, Lee Y H, Choi Y S. et al . Heterogeneous expression of Ku70 in human tissues is associated with morphological and functional alterations of the nucleus.  J Pathol. 2002;  198 121-130
• 17 Konttinen Y T, Käsnä-Ronkainen L. Sjögren’s syndrome: viewpoint on pathogenesis.  Scand J Rheumatol. 2002;  Suppl 116 15-22
• 18 Hoeijmakers J H. Genome maintenance mechanisms for preventing cancer.  Nature. 2001;  411 366-374
• 19 Tornwall J, Konttinen Y T, Tuominen R K. et al . Protein kinase C expression in salivary gland acinar epithelial cells in Sjogren’s syndrome.  Lancet. 1997;  349 1814-1815
• 20 Matassa A A, Carpenter L, Biden T J. et al . PKCdelta is required for mitochondrial-dependent apoptosis in salivary epithelial cells.  J Biol Chem. 2001;  276 29 719-29 728
• 21 Patel Y I, McHugh N J. Apoptosis-new clues to the pathogenesis of Sjogren’s syndrome?.  Rheumatology. 2000;  39 119-121
• 22 Manganelli P, Fietta P. Apoptosis and Sjogren syndrome.  Semin Arthritis Rheum. 2003;  33 49-65
• 23 Ohlsson M, Skarstein K, Bolstad A I. et al . Fas-induced apoptosis is a rare event in Sjogren’s syndrome.  Lab Invest. 2001;  81 95-105
• 24 Mariette X, Sibilia J, Roux S. et al . A new defensive mechanism to prevent apoptosis in salivary ductal cells from patients with Sjögren’s syndrome: over-expression of p53 and p21.  Rheumatol. 2002;  41 96-99
• 25 Smeenk R J. Antinuclear antibodies: cause of disease or caused by disease?.  Rheumatol. 2000;  39 581-584
• 26 Casciola-Rosen L, Andrade F, Ulanet D. et al . Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity.  J Exp Med. 1999;  190 815-826
• 27 James J A, Harley J B, Scofield R H. Role of viruses in systemic lupus erythematosus and Sjogren syndrome.  Curr Opin Rheumatol. 2001;  13 370-376
• 28 Baboonian C, Venables P J, Booth J. et al . Virus infection induces redistribution and membrane localization of the nuclear antigen La (SS-B): a possible explanation for autoimmunity.  Clin Exp Immunol. 1989;  78 454-459
• 29 Altshuler E L. Antiquity of Epstein-Barr virus, Sjogren’s syndrome, and Hodgkin’s disease-historical concordance and discordance.  J Natl Cancer Inst. 1999;  91 1512-1513
• 30 Inoue H, Tsubota K, Ono M. et al . Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific autoantigen in Sjogren’s syndrome.  J Immunol. 2001;  166 5801-5809
• 31 Bachmann M, Hilker M, Grolz D. et al . Different La/SS-B mRNA isoforms are expressed in salivary gland tissue of patients with primary Sjögren’s syndrome.  J Autoimmun. 1996;  9 757-766
• 32 Ohlsson M, Jonsson R, Brokstad K A. Subcellular distribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjögren’s syndrome.  Scand J Immunol. 2002;  56 456-469
• 33 van Woerkom J M, Geertzema J G, Nikkels P G. et al . Expression of Ro/SS-A and La/SS-B determined by immunohistochemistry in healthy, inflamed and autoimmune diseased human tissues: a generalized phenomenon.  Clin Exp Rheumatol. 2004;  22 285-292
• 34 Rolink A G, Melchers F. BAFFled B cells survive and thrive: roles of BAFF in B-cell development.  Curr Opin Immunol. 2002;  14 266-275
• 35 Groom J, Kalled S L, Cutler A H. et al . Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome.  J Clin Invest. 2002;  109 59-68
• 36 Szodoray P, Jellestad S, Teague M O. et al . Attenuated apoptosis of B cell activating factor-expressing cells in primary Sjogren’s syndrome.  Lab Invest. 2003;  83 357-365
• 37 Stott D I, Hiepe F, Hummel M. et al . Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjogren’s syndrome.  J Clin Invest. 1998;  102 938-946
• 38 Hansen A, Odendahl M, Reiter K. et al . Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjogren’s syndrome.  Arthritis Rheum. 2002;  46 2160-2171
• 39 Larsson Å, Bredberg A, Henriksson G. et al . Immunohistochemistry of the B cell component in lower lip salivary glands of Sjögren’s syndrome and healthy subjects.  Scand J Immunol. 2005;  61 98-107
• 40 Abbas AK, Lichtman AH (eds) .Cellular and Molecular Immunology (5th ed.). Philadelphia; W.B. Saunders 2003
• 41 Fox R I, Kang H I, Ando D. et al . Cytokine mRNA expression in salivary gland biopsies of Sjogren’s syndrome.  J Immunol. 1994;  152 5532-5539
• 42 Koski K H, Janin A, Humphreys-Beher M G. et al . Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjogrens’s syndrome.  Clin Exp Rheumatol. 2001;  19 131-137
• 43 Moutsopoulos H M. Sjogren’s syndrome: autoimmune epithelitis.  Clin Immunol Immunopathol. 1994;  72 162-165
• 44 Manoussakis M N, Dimitriou I D, Kapsogeorgou E K. et al . Expression of B7 costimulatory molecules by salivary gland epithelial cells in patients with Sjogren’s syndrome.  Arthritis Rheum. 1999;  42 229-239
• 45 Kassi E, Moutsatsou P, Sekeris C E. et al . Oestrogen receptors in cultured epithelial cells from salivary glands of Sjogren’s syndrome patients.  Rheumatol. 2003;  42 1120-1122
• 46 Wang H, Yu M, Ochani M. et al . Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.  Nature. 2003;  421 384-388
• 47 Borovikova L V, Ivanova S, Zhang M. et al . Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.  Nature. 2000;  405 458-462
• 48 Tracey K J. The inflammatory reflex.  Nature. 2002;  420 853-859
• 49 Manthorpe R, Benoni C, Jacobsson L. et al . Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjogren’s syndrome?.  Ann Rheum Dis. 2000;  59 54-60
• 50 Waterman S A, Gordon T P, Rischmueller M. Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjogren’s syndrome.  Arthr Rheum. 2000;  43 1647-1654
• 51 Fox R I, Stern M. Sjögren’s syndrome: mechanisms of pathogenesis involve interaction of immune and neurosecretory systems.  Scand J Rheumatol. 2002;  Suppl 116 3-13