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Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lymphoma development in patients with Sjögren’s syndrome
  1. Efstathia K Kapsogeorgou1,2,
  2. Aristea Papageorgiou1,2,
  3. Athanase D Protogerou1,2,
  4. Michael Voulgarelis1,2,
  5. Athanasios G Tzioufas1,2
  1. 1Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  2. 2Academic Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  1. Correspondence to Professor Athanasios G Tzioufas, Department of Pathophysiology, School of Medicine, National University of Athens, Athens 11527, Greece; agtzi{at}med.uoa.gr

Abstract

Objectives Development of non-Hodgkin’s lymphoma (NHL) is the major adverse outcome of Sjögren’s syndrome (SS) affecting both morbidity and mortality. Preliminary evidence suggested that, although not deregulated compared with sicca controls, miR200b-5p levels are decreased in the minor salivary glands (MSGs) of SS patients with NHL. The aim of the current study was to evaluate the MSG expression of miR200b-5p in SS-associated NHLs and its potential predictive value for the identification of patients with SS susceptible to develop NHL.

Methods miR200b-5p expression was investigated in MSG tissues of patients with SS who were at: (A) low risk and did not develop NHL during follow-up (n=27; median follow-up time on biopsy performance, range: 8.9 years, 1.33–14 years), (B) high-risk and diagnosed with NHL during follow-up (prelymphoma; n=17; median follow-up to until lymphoma diagnosis, range: 3.67 years, 0.42–8.5 years) and (C) had NHL (n=35), as well as non-SS sialadenitis controls (sarcoidosis and hepatitis C virus (HCV) infection, four each). The differential miR200b-5p expression, correlations with disease features and its discriminative/predictive value, was evaluated by appropriate statistical approaches.

Results The MSG levels of miR200b-5p were significantly downregulated in patients with SS who will develop or have NHL and strongly discriminated (p<0.0001) them from those without lymphoma or non-SS sialadenitis. Furthermore, they were reduced long before clinical onset of lymphoma, did not significantly change on transition to lymphoma and, importantly, were proved strong independent predictors of patients who will develop NHL (p<0.0001).

Conclusions These findings support that miR200b-5p levels in MSGs represent a novel predictive and possibly pathogenetic mechanism-related factor for the development of SS-associated NHL, since its expression is impaired years before lymphoma clinical onset.

  • sjøgren’s syndrome
  • autoimmune diseases
  • autoimmunity

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors EKK designed the study, performed the experiments, analysed the data and wrote the paper. AP evaluated the clinical data of patients with non-Hodgkin’s lymphoma (NHL) patients, ADP performed statistical analyses, MV evaluated the clinical data of patients with NHL and contributed in data analysis and manuscript preparation and AGT designed the study and wrote the paper. AGT and EKK had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding The research has been financed by grants of the Research Grant from the Greek Rheumatology Society and Professional Association of Rheumatologists and the European-funded multicentric protocol ’HARMONIzation and integrative analysis of regional, national and international Cohorts on primary Sjögren’s Syndrome (pSS) towards improved stratification, treatment and health policy making' (HARMONICSS; H2020-SC1-2016; grant agreement no: 731944).

  • Competing interests AGT has received research grants from Novartis, Pfizer, UCB, AbbVie and GSK pharmaceutical companies, through the National and Kapodistrian University of Athens, outside the submitted work.

  • Patient consent Not required.

  • Ethics approval Ethics Committee of School of Medicine, National and Kapodistrian University of Athens, Greece (protocol no: 1516023881).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There are no additional unpublished data related to the study.

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