Biomarkers in Primary Sjögren's Syndrome

NCT03765593 | Unknown

• 1 other identifier: 3398
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The clinical spectrum of primary Sjogren Syndrome (pSS)ranges from sicca syndrome to systemic involvement (extraglandular manifestations), including a large number of manifestations that may be the form of presentation or appear after the disease is diagnosed, and that clearly mark the prognosis of the disease. Gene expression levels of Interferon (INF) and B Lymphocyte Biomarkers as Markers of Systemic Affectation and Lymphoproliferative Disease in, together with clinical and laboratory parameters, will provide significant information about the risk of developing hematological neoplasms in patients with pSS at different stages of the disease, and lead to better management of the disease treatment and therapeutic behaviors. Using the proposed technique allows us to study the gene expression at the mRNA level of each biomarker, which allows us to anticipate the irreversible changes that take place due to the progress of the pathology in progress, since the molecular changes precede the histological changes and in the pathological diagnosis.

Conditions

Primary Sjögren Syndrome; Lymphoma, Non-Hodgkin

Keywords

Primary Sjogren Syndrome; Lymphoma; Biomarker

Outcome Measures

Primary Outcomes (3)

• Gene expression levels in immune cells in salivary gland biopsy samples from participants with and without pSS

  To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).

  Up to 24 months

• Gene expression levels in immune cells in blood samples from participants with and without pSS

  To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).

  Up to 24 months

• Gene expression levels in immune cells in saliva samples from participants with and without pSS

  To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).

  Up to 24 months

Secondary Outcomes (4)

• Immunoglobulins

  Up to 24 months

• Complement levels C3 and C4

  Up to 24 months

• Rheumatoid Factor

  Up to 24 months

• Cryoglobulins

  Up to 24 months

Study Arms (4)

Study group 1

Immunopositive primary SS (Anti-SSA +/anti-Ro+) will receive salivary gland biopsy.

Procedure: Biopsy Salivary Gland

Study group 2

Immunonegative primary SS (Anti-SSA -/anti Ro-, biopsy Chisholm-Mason 3-4) will receive salivary gland biopsy.

Procedure: Biopsy Salivary Gland

Study group 3

Non-autoimmune sicca syndrome (Anti-SSA/anti Ro-, biopsy Chisholm-Mason 2 o less) will receive salivary gland biopsy.

Procedure: Biopsy Salivary Gland

Control group

Patients who have sicca syndrome but do not meet the classification criteria of Sjögren's syndrome, therefore, at the time of evaluating these patients to determine whether or not they have the disease are what will serve as controls since according to the usual diagnostic process, the same studies will be carried out as for patients with the proposed disease. Will receive salivary gland biopsy.

Procedure: Biopsy Salivary Gland

Interventions

Biopsy Salivary Gland PROCEDURE

A minor salivary gland biopsy will be performed at lower lip, with the minimally invasive technique that is carried out in Rheumatology Unit as a routine procedure for the diagnosis of pSS, from there it will be taken between 2-3 glands for the study. RNAlater®(Ambion, Inc., Texas, United States of America) will be stored in solution for the stabilization and preservation of RNA at -80ºC.

Control group; Study group 1; Study group 2; Study group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants with sicca and primary Sjogren Syndrome will be recruited from multiple sites.

You may qualify if:

• Patients: cross sectionally patients will be included for clinical suspicion of primary SS or with the diagnosis already established in Rheumatology unit.
• Age \> 18 years
• Informed consent of the patient.

You may not qualify if:

• Impossibility of obtaining consent (cognitive impairment, other causes).
• Associated systemic autoimmune or rheumatological diseases.
• Chronic viral infections (HCV, HBV, HIV).

Sponsors & Collaborators

• National Council of Scientific and Technical Research, Argentina: lead

Related Publications (22)

• Retamozo S, Flores-Chavez A, Consuegra-Fernandez M, Lozano F, Ramos-Casals M, Brito-Zeron P. Cytokines as therapeutic targets in primary Sjogren syndrome. Pharmacol Ther. 2018 Apr;184:81-97. doi: 10.1016/j.pharmthera.2017.10.019. Epub 2017 Oct 29.

  PMID: 29092775 BACKGROUND

• Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR, Costa J, Decker JL, Chused TM. Increased risk of lymphoma in sicca syndrome. Ann Intern Med. 1978 Dec;89(6):888-92. doi: 10.7326/0003-4819-89-6-888.

  PMID: 102228 BACKGROUND

• Jonsson R, Gordon TP, Konttinen YT. Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjogren's syndrome. Curr Rheumatol Rep. 2003 Aug;5(4):311-6. doi: 10.1007/s11926-003-0010-z.

  PMID: 14531959 BACKGROUND

• Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren's syndrome. Arthritis Rheum. 2002 Mar;46(3):741-7. doi: 10.1002/art.10221.

  PMID: 11920410 BACKGROUND

• Brito-Zeron P, Retamozo S, Gheitasi H, Ramos-Casals M. Erratum to: Treating the Underlying Pathophysiology of Primary Sjogren Syndrome: Recent Advances and Future Prospects. Drugs. 2016 Dec;76(18):1799. doi: 10.1007/s40265-016-0669-x. No abstract available.

  PMID: 27905085 BACKGROUND

• Rose T, Grutzkau A, Hirseland H, Huscher D, Dahnrich C, Dzionek A, Ozimkowski T, Schlumberger W, Enghard P, Radbruch A, Riemekasten G, Burmester GR, Hiepe F, Biesen R. IFNalpha and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Ann Rheum Dis. 2013 Oct;72(10):1639-45. doi: 10.1136/annrheumdis-2012-201586. Epub 2012 Oct 31.

  PMID: 23117242 BACKGROUND

• Martin T, Weber JC, Levallois H, Labouret N, Soley A, Koenig S, Korganow AS, Pasquali JL. Salivary gland lymphomas in patients with Sjogren's syndrome may frequently develop from rheumatoid factor B cells. Arthritis Rheum. 2000 Apr;43(4):908-16. doi: 10.1002/1529-0131(200004)43:43.0.CO;2-K.

  PMID: 10765938 RESULT

• Quartuccio L, Baldini C, Bartoloni E, Priori R, Carubbi F, Corazza L, Alunno A, Colafrancesco S, Luciano N, Giacomelli R, Gerli R, Valesini G, Bombardieri S, De Vita S. Anti-SSA/SSB-negative Sjogren's syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution. Autoimmun Rev. 2015 Nov;14(11):1019-22. doi: 10.1016/j.autrev.2015.07.002. Epub 2015 Jul 8.

  PMID: 26162302 RESULT

• Quartuccio L, Salvin S, Fabris M, Maset M, Pontarini E, Isola M, De Vita S. BLyS upregulation in Sjogren's syndrome associated with lymphoproliferative disorders, higher ESSDAI score and B-cell clonal expansion in the salivary glands. Rheumatology (Oxford). 2013 Feb;52(2):276-81. doi: 10.1093/rheumatology/kes180. Epub 2012 Aug 9.

  PMID: 22879463 RESULT

• Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999 Jul 9;285(5425):260-3. doi: 10.1126/science.285.5425.260.

  PMID: 10398604 RESULT

• Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999 Jun 7;189(11):1747-56. doi: 10.1084/jem.189.11.1747.

  PMID: 10359578 RESULT

• Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, Kimberly R. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren's syndrome. Ann Rheum Dis. 2003 Feb;62(2):168-71. doi: 10.1136/ard.62.2.168.

  PMID: 12525388 RESULT

• Theander E, Vasaitis L, Baecklund E, Nordmark G, Warfvinge G, Liedholm R, Brokstad K, Jonsson R, Jonsson MV. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome. Ann Rheum Dis. 2011 Aug;70(8):1363-8. doi: 10.1136/ard.2010.144782.

  PMID: 21715359 RESULT

• Lavie F, Miceli-Richard C, Quillard J, Roux S, Leclerc P, Mariette X. Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjogren's syndrome. J Pathol. 2004 Apr;202(4):496-502. doi: 10.1002/path.1533.

  PMID: 15095277 RESULT

• Szodoray P, Alex P, Jonsson MV, Knowlton N, Dozmorov I, Nakken B, Delaleu N, Jonsson R, Centola M. Distinct profiles of Sjogren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF. Clin Immunol. 2005 Nov;117(2):168-76. doi: 10.1016/j.clim.2005.06.016. Epub 2005 Aug 26.

  PMID: 16126006 RESULT

• Daridon C, Devauchelle V, Hutin P, Le Berre R, Martins-Carvalho C, Bendaoud B, Dueymes M, Saraux A, Youinou P, Pers JO. Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjogren's syndrome. Arthritis Rheum. 2007 Apr;56(4):1134-44. doi: 10.1002/art.22458.

  PMID: 17393395 RESULT

• Hjelmervik TO, Petersen K, Jonassen I, Jonsson R, Bolstad AI. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjogren's syndrome patients from healthy control subjects. Arthritis Rheum. 2005 May;52(5):1534-44. doi: 10.1002/art.21006.

  PMID: 15880807 RESULT

• Wildenberg ME, van Helden-Meeuwsen CG, van de Merwe JP, Drexhage HA, Versnel MA. Systemic increase in type I interferon activity in Sjogren's syndrome: a putative role for plasmacytoid dendritic cells. Eur J Immunol. 2008 Jul;38(7):2024-33. doi: 10.1002/eji.200738008.

  PMID: 18581327 RESULT

• Brkic Z, Maria NI, van Helden-Meeuwsen CG, van de Merwe JP, van Daele PL, Dalm VA, Wildenberg ME, Beumer W, Drexhage HA, Versnel MA. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression. Ann Rheum Dis. 2013 May;72(5):728-35. doi: 10.1136/annrheumdis-2012-201381. Epub 2012 Jun 26.

  PMID: 22736090 RESULT

• Nezos A, Gravani F, Tassidou A, Kapsogeorgou EK, Voulgarelis M, Koutsilieris M, Crow MK, Mavragani CP. Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis. J Autoimmun. 2015 Sep;63:47-58. doi: 10.1016/j.jaut.2015.07.002. Epub 2015 Jul 14.

  PMID: 26183766 RESULT

• Rose T, Szelinski F, Lisney A, Reiter K, Fleischer SJ, Burmester GR, Radbruch A, Hiepe F, Grutzkau A, Biesen R, Dorner T. SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjogren's syndrome. RMD Open. 2016 Dec 30;2(2):e000292. doi: 10.1136/rmdopen-2016-000292. eCollection 2016.

  PMID: 28123773 RESULT

• Barone F, Bombardieri M, Manzo A, Blades MC, Morgan PR, Challacombe SJ, Valesini G, Pitzalis C. Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjogren's syndrome. Arthritis Rheum. 2005 Jun;52(6):1773-84. doi: 10.1002/art.21062.

  PMID: 15934082 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Salivary gland, saliva, blood samples

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Maria Soledad Retamozo, MD, PhD

  INICSA-Universidad Nacional de Córdoba-CONICET, Córdoba, Argentina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Soledad Retamozo, MD, PhD

CONTACT

005493516981622; soleretamozo@hotmail.com

Eduardo Cuestas, MD, PhD

CONTACT

005493516609303; eduardo.cuestas@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: December 5, 2018
• Study Start: March 1, 2019
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2021
• Last Updated: December 5, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share