Pathogenesis Of Autoimmune Rheumatic Diseases Research Articles

Sjögren's syndrome: viewpoint on pathogenesis

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 to the etiology and pathogenesis of autoimmune rheumatic diseases. In spite of this, consensus if often taken as a truth, which may hamper the 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) after initiation, a straightforward sequence of events follows: a) salivary gland epithelial cells are disrupted, b) T lymphocytes migrate to and are activated in the glands, c) B cells get the help they need and start to produce SS and RF autoantibodies, which processes lead to structural destruction and loss of acinar cells and, thus, to sicca symptoms (an example of the linear, step-by-step "computer" logic). The problems inherent to this view include: 1) why women? (gender aspect), 2) why at the age of 50? (chronobiologic aspect), 3) is the normal immune system 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 HLA background? (autoimmune aspect), 4) are the retroviral diseases really similar to SS? (exogenous vs endogenous causes), 5) is our current view compatible 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 and pass in normal glands through normal, immunologically competent lymphocyte foci and/or ectopic lymphatic tissue. Acinar cell degeneration/death may increase upon 2) aging and acinar cell renewal and well-being may be hampered by age-dependent deficiencies in the trophic 3) neuro-endocrine support. In a proper immunogenetic setting, a) marker autoantibodies (e.g. RF, SS-A/Ro, SS-B/La), useful in the diagnosis, are produced. However, sicca symptoms/SS develop only if muscarinic receptor or other b) pathogenetic autoantibodies disrupting 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 your own one!

Sjögren's syndrome: viewpoint on pathogenesis

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!

Interleukin-13 (IL-13)in autoimmune rheumatic diseases: relationship with autoantibody profile

The production of rheumatoid factor (RF) and antinuclear antibody by B-cells could depend on different cytokines action. We evaluated IL-13 serum levels in 230 patients with autoimmune rheumatic diseases including rheumatoid arthritis (RA) [M/F=22/62; mean age=55.2 (25-76) yrs; mean disease duration = 116 (5-605) months], SLE [M/F=17/97; mean age=38.3 (15-70) yrs; mean disease duration = 77 (1-456) months], Sjogren's syndrome (SS) [M/F=2/50; mean age = 55.2 (26-81) yrs; mean disease duration = 82 (3-540) months], and systemic sclerosis (ScS) [M/F = 1/31; mean age=50.6 (20-73) yrs; mean disease duration = 113 (12-276) months], in order to investigate the relationship of this cytokine with the autoantibody profile. Serum levels of IL-13 (pg/ml) were significantly increased in patients with RA (P < 0.00003), with SLE (P < 0.03), with SS (P < 0.0007), with ScS (P < 0.025) as compared to controls. IL-13 serum levels correlated with those of RF in RA (P < 0.00001), SLE (P < 0.003) and ScS (P < 0.03). IL-13 levels were higher in RA (P < 0.0002), SLE (P < 0.004) and ScS (P < 0.05) patients with RF than patients without RF. SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (P < 0.036). No statistically significative correlation was found between IL-13 levels and any other antinuclear autoantibody or total immunoglobulin levels or main clinical features of each disease. This study suggests that IL-13 may be involved in the pathogenesis of autoimmune rheumatic diseases, with a relevant role on RF production. In SS, the lack of correlation between IL-13 and RF is probably due to the peculiar characteristics of this antibody in the disease. We can conclude that the mechanisms involved in RF synthesis recognise different pathways depending on the underlying autoimmune disease.