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| Author(s): |
Victor Adriano de Oliveira Martins
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2022-06-08 |
| Examining board members: |
Sandra Gofinet Pasoto;
Marília Trierveiler Martins;
Samuel Katsuyuki Shinjo;
Virgínia Fernandes Moça Trevisani
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| Advisor: | Sandra Gofinet Pasoto |
| Abstract | |
Introduction: Primary Sjögren\'s syndrome (pSS) is a chronic inflammatory systemic disease that mainly affects the lacrimal and salivary glands. pSS has an autoimmune pathophysiology and is associated with the production of autoantibodies, particularly anti-Ro/SS-A and anti-La/SS-B. Recently, our group described a high frequency of anti-DNase I in serum of pSS patients. This finding is interesting considering the recent description of a reduced DNase I activity in tears of patients with xerophthalmia of various causes, which would result in an accumulation of extracellular DNA, which could contribute to the inflammatory process on the ocular surface. It is possible that such findings also occur in the oral cavity. In addition, oral infectious foci can aggravate the salivary gland dysfunction in an experimental model. However, there are few studies evaluating the impact of primary care dental treatment (PDC) on pSS. Objectives: To evaluate the presence of anti-DNase I antibodies and the activity of this enzyme in saliva and serum of pSS patients, and the impact of PDC on the degree of xerostomia, salivary flow rates and salivary cytokine profile. Methods: Fifty-two pSS patients [American-European Consensus Group (2002) and/or ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) (2016) classification criteria] and 52 control individuals without systemic autoimmune diseases, matched for sex, age and race and with comparable socioeconomic class to pSS patients were included in a prospective study. At entry (D0), all participants were evaluated using a standardized clinical protocol, which included the Xerostomia Inventory (XI). pSS patients were also evaluated using the EULAR Sjögren\'s Syndrome Reported Index (ESSPRI) and the EULAR Sjögren\'s Syndrome Disease Activity Index (ESSDAI). The Decayed, Missing and Filled Teeth (DMFT) index was calculated, periodontitis (American Academy of Periodontology, 2000) and other oral inflammatory foci were evaluated for all participants; in addition, unstimulated and stimulated salivary flows rates were measured. At inclusion, serum, plasma and saliva samples were also collected from pSS patients and controls for detection of anti-DNase I IgG, determination of serum and salivary concentrations of DNase I and its activity. Salivary levels of tumor necrosis factor- (TNF-), interleukin (IL)-1, IL-6, resistin, B-cell activating factor (BAFF) and metalloproteinase-9 (MMP-9) were also measured. After these collections, PDC treatment was performed on D0, and the clinical and laboratorial assessments were repeated three months after PDC (D90). Results: All 52 pSS patients and 49 controls completed clinical and dental evaluations on D0 and D90. The pSS and control groups were similar in demographic characteristics: age (P = 0.800), sex (P = 1.000), race (P = 1.000), and socioeconomic status (P = 0.821). In contrast, DMFT index was higher in pSS patients than in controls: 13.3 8.2 vs. 8.6 6.2 (P = 0.002), respectively. Non-carious cervical lesions were also more frequent in pSS patients compared to controls (P = 0.008). In contrast, periodontal parameters and periodontitis frequency were comparable in both groups (P > 0.05). Serum anti- DNase I was more frequent in pSS patients (63.5%) than in control individuals (11.5%) (P < 0.001). Furthermore, we demonstrated the presence of anti-DNase I and a reduced activity of this enzyme in saliva of pSS patients. Assessment of pSS patients on D0 and three months after PDC treatment (D90) showed significant improvement in unstimulated (P < 0.001) and stimulated (P = 0.001) salivary flow rates. There was no improvement in XI values (P = 0.285), but 26.9% of pSS patients showed clinically significant improvement (reduction of at least 6 points in XI). ESSPRI and ESSDAI values remained unchanged on D0 and D90 (P > 0.05), as well as salivary concentrations of TNF-, IL-1, IL-6, resistin, BAFF and MMP-9 (P 0 .05). Conclusions: DMFT index was higher in pSS patients than in controls without systemic autoimmune diseases, confirming the relevance of carious lesions in this disease. We demonstrated the presence of anti-DNase I antibody in serum and saliva of pSS patients, as well as a decreased activity of this enzyme in saliva, which, in hypothesis, may contribute to the pathophysiology of salivary gland damage. PDC treatment promoted significant improvement in unstimulated and stimulated salivary flow rates in pSS patients. This finding, although without improvement of XI, has the potential to contribute to the reduction of oral complications in pSS, and reinforces its recommendation for these patients (AU) | |
| FAPESP's process: | 18/09937-9 - Analysis of the immune profile of saliva and serum of patients with primary Sjogren's Syndrome |
| Grantee: | Victor Adriano de Oliveira Martins |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |