Immune Profile of Saliva and Serum of Patients With Primary Sjögren´s Syndrome (pSS)

Analysis of the Immune Profile of Saliva and Serum of Patients With Primary Sjögren´s Syndrome

Primary Sjögren's syndrome (pSS) is a chronic systemic inflammatory disease, which mainly affects the lacrimal and salivary glands, leading to sicca syndrome. pSS has a probable autoimmune etiology, with the production of several autoantibodies such as antinuclear antibodies (ANA), anti-Ro/SS-A, anti-La/SS-B, rheumatoid factor (RF) and cryoglobulins. Recently, our group described a high frequency of antibodies directed to DNase I in the serum of pSS patients and these antibodies were associated with the presence of the anti-Epstein-Barr (EBV) early antigen diffuse (anti-EA-D). This finding becomes interesting considering the recent description of reduction of DNase I activity in the tear of patients with xerophthalmia of different causes, which would result in an accumulation of extracellular DNA and neutrophilic inflammatory infiltrate on the ocular surface. This hypothesis is reinforced by the observation that treatment with DNase I as eye drops results in clinical improvement of dry eye. In addition, it has been shown that periodontal disease is an aggravating factor of xerostomia in pSS, as it leads to a chronic inflammatory process and, consequently, to the destruction of minor salivary glands. Therefore, the objective of the present study will be to evaluate the presence of antibodies directed to DNase I in the saliva and serum of pSS patients and its possible capacity of inhibition of the enzyme before and after treatment of periodontal disease. Such findings will be correlated with the presence of periodontal disease, with the glandular and extraglandular manifestations of SSp and also with the presence of EBV DNA in the serum and oral lavage of these patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Procedure: Periodontal scaling

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-000
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • São Paulo, Brazil
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with primary Sjögren's syndrome according to 2016 EULAR/ACR Classification Criteria, and healthy people without any rheumatic disease/symptoms of sicca syndrome
• Patients regularly followed at the Sjögren's Syndrome outpatient clinic of Rheumatology Division

Exclusion Criteria:

• Use of drugs that cause oral dryness (mainly antidepressants and antihistamines).
• Patients with history of head and neck radiation therapy.
• Current smoking.
• Pregnancy and/or lactation.
• History of periodontal treatment for at least 6 months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: pSS patients; We will evaluate 40 patients with pSS (EULAR/ACR Classification Criteria, 2016) of both sexes before and after periodontal disease treatment.	Procedure: Periodontal scaling; Periodontal scaling and root planing; Other Names: Clinical periodontal disease treatment
Active Comparator: Healthy individuals; We will evaluate 40 healthy controls before and after periodontal disease treatment.	Procedure: Periodontal scaling; Periodontal scaling and root planing; Other Names: Clinical periodontal disease treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Xerostomia Inventory Score at 3 months	Change from baseline Xerostomia Inventory Score at 3 months. An international validated questionnaire of dry mouth symptoms ranging from 11 to 55 points.	Change from baseline Xerostomia Inventory Score at 3 months
Change from baseline activity of DNAse I enzyme in saliva at 3 months	Change from baseline activity of DNAse I enzyme in saliva at 3 months measured by Enzyme-Linked Immunosorbent Assay (ELISA).	Change from baseline activity of DNAse I enzyme in saliva at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline interleukin-1b (IL-1b) concentration in saliva at 3 months	Change from baseline interleukin-1b (IL-1b) concentration in saliva at 3 months measured by Luminex Assay.	Change from baseline interleukin-1b (IL-1b) concentration in saliva at 3 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• Ambrosio LM, Rovai ES, Franca BN, Balzarini DA, Abreu IS, Lopes SB, Nunes TB, Lourenco SV, Pasoto SG, Saraiva L, Holzhausen M. Effects of periodontal treatment on primary sjogren's syndrome symptoms. Braz Oral Res. 2017 Jan 16;31:e8. doi: 10.1590/1807-3107BOR-2017.vol31.0008.
• Nakamura-Kiyama M, Ono K, Masuda W, Hitomi S, Matsuo K, Usui M, Nakashima K, Yokota M, Inenaga K. Changes of salivary functions in experimental periodontitis model rats. Arch Oral Biol. 2014 Feb;59(2):125-32. doi: 10.1016/j.archoralbio.2013.11.001. Epub 2013 Nov 8.
• Martins VAO, Floriano TF, Leon EP, Villamarin LEB, Deveza GBH, Aikawa NE, Silva CAA, Kupa LVK, Peres MPSM, Braz-Silva PH, Bonfa E, Pasoto SG. Primary dental care treatment in primary Sjogren's syndrome: a possible role in improving salivary flow rate. Clin Exp Rheumatol. 2022 Dec;40(12):2258-2267. doi: 10.55563/clinexprheumatol/kfn28h. Epub 2022 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): October 13, 2021
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 18, 2018

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: IPS - pSS; 2015/03756-4 (Other Grant/Funding Number: FAPESP); 2018/09937-9 (Other Grant/Funding Number: FAPESP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No