Biomarkers in Primary Sjögren's Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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This project, address the value of these proposed biomarkers in pSS with regard to disease activity and risk stratification of pSS subsets. The investigator's group aim to determine if the proposed biomarkers and their gene expression in saliva, peripheral blood and minor salivary gland samples in patients with pSS are increased to know the degree of their usefulness in daily clinical practice, to indicate which patients have a highest risk of developing a hematological malignancy and to know if these biomarkers are useful to recognize patients who have greater activity of the disease to be able to use it in the follow-up of the disease and as a future responder of the new biological therapies against B cells, INF and monocytes. Gene expression is a highly regulated mechanism that controls the function and adaptability of all living cells. The field of gene expression analysis has undergone important advances in biomedical research. Today, quantification techniques of mRNA expression have led to improvements in the identification of the gene and the sub-classification of the disease, for example, the expression of specific genes (mRNA) can be quantified by reverse transcription and PCR in quantitative real time. This is the most sensitive technique available to detect and quantify mRNA, where extremely small sample sizes can be used in mRNA quantification. Molecular changes precede histological changes and clinicians in the diagnosis of a pathology. For this reason, studying gene expression at the mRNA level allows us to anticipate irreversible changes that take place due to the progress of the pathology in progress.

Official Title
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Gene Expression of Interferon (INF) and B Lymphocyte Biomarkers as Markers of Systemic Affectation and Lymphoproliferative Disease in Primary Sjögren's Syndrome

Conditions
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Primary Sjögren Syndrome, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Procedure: Biopsy Salivary Gland


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: cross sectionally patients will be included for clinical suspicion of primary SS or with the diagnosis already established in Rheumatology unit. The following inclusion criteria will be applied to the study: Age > 18 years Informed consent of the patient. Exclusion Criteria: Impossibility of obtaining consent (cognitive impairment, other causes). Associated systemic autoimmune or rheumatological diseases. Chronic viral infections (HCV, HBV, HIV).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group 1<br>Immunopositive primary SS (Anti-SSA +/anti-Ro+) will receive salivary gland biopsy. | Procedure: Biopsy Salivary Gland<br>* 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.<br>|
| Study group 2<br>Immunonegative primary SS (Anti-SSA -/anti Ro-, biopsy Chisholm-Mason 3-4) will receive salivary gland biopsy. | Procedure: Biopsy Salivary Gland<br>* 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.<br>|
| Study group 3<br>Non-autoimmune sicca syndrome (Anti-SSA/anti Ro-, biopsy Chisholm-Mason 2 o less) will receive salivary gland biopsy. | Procedure: Biopsy Salivary Gland<br>* 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.<br>|
| Control group<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulins | The change from baseline in IgG, IgM and IgA levels at 24 months. | Up to 24 months | 
| Complement levels C3 and C4 | The change from baseline in complement levels at 24 months. | Up to 24 months | 
| Rheumatoid Factor | The change from baseline in titer of rheumatoid factors at 24 months. | Up to 24 months | 
| Cryoglobulins | The change from baseline in titer of cryoglobulins at 24 months. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Sjogren Syndrome, Lymphoma, Biomarker