Sjögren's syndrome: viewpoint on pathogenesis

Abstract

Objective: To critically consider the public opinion/consensus on SS formulated by opinion leaders and textbook chapters.Rationale: Although our clinical work is based on evidence-based medicine, it is obvious that we do not have evidence-based solutions tothe etiology and pathogenesis of autoimmune rheumatic diseases. In spite of this, consensus if often taken as a truth, which may hamperthe production, funding and/or publication of new and original ideas and views.Methods: Comparison of the classic view with one of the many other possible views.Results: The consensus view states that 1) SS is initiated and/or caused by an exogenous agent, probably some type of retrovirus, and 2) afterinitiation, a straightforward sequence of events follows: a) salivary gland epithelial cells are disrupted, b) T lymphocytes migrate to and areactivated in the glands, c) B cells get the help they need and start to produce SS and RF autoantibodies, which processes lead to structuraldestruction and loss of acinar cells and, thus, to sicca symptoms (an example of the linear, step-by-step "computer" logic). The problemsinherent to this view include: 1) why women? (gender aspect), 2) why at the age of 50? (chronobiologic aspect), 3) is the normal immunesystem in SS only responding to normal (formely sequestrated) autoantigens? Is the loss of exocrine gland function really caused by"autoimmune" destruction? - or do the SS-autoantibodies and lymphocyte infiltrates only represent markers in an appropriate HLAbackground? (autoimmune aspect), 4) are the retroviral diseases really similar to SS? (exogenous vs endogenous causes), 5) is our current viewcompatible with unexpected, future findings? Is the textbook interpretation the final truth (evolutionary aspect of our view on pathogenesis).Conclusion: The tubuloalveolar exocrine glands may be seen as 1) locus minoris resistentiae for normal oral microbial flora and immuneinflammatory attacks at the normal environment-host interface. Apoptotic and/or necrotic cells are released into the intraluminal space andpass in normal glands through normal, immunologically competent lymphocyte foci and/or ectopic lymphatic tissue. Acinar celldegeneration/death may increase upon 2) aging and acinar cell renewal and well-being may be hampered by age-dependent deficiencies inthe trophic 3) neuro-endocrine support. In a proper immunogenetic setting, a) marker autoantibodies (e.g. RF, SS-A/Ro, SS-B/La), usefulin the diagnosis, are produced. However, sicca symptoms/SS develop only if muscarinic receptor or other b) pathogenetic autoantibodiesdisrupting the normal neuronal-to acinar cell communication are also produced. c) Systemic symptoms could be produced on neuroendocrine,chronobiologic and autoimmune basis. Other professionals are invited to entertain their own views on the pathogenesis of SS – make yourown one!