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Association between memory B-cells and clinical and immunological features of primary Sjögren’s syndrome and Sicca patients

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Abstract

B-cells play a pivotal role in primary Sjögren’s syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

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Acknowledgements

The first author gratefully acknowledges Academia Cuf/José de Mello Saúde and Sociedade Portuguesa de Reumatologia for its financial support.

Funding

The project was partially financed by Academia Cuf/José de Mello Saúde, Carnaxide, Portugal, and Sociedade Portuguesa de Reumatologia, Lisbon, Portugal.

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Authors and Affiliations

  1. CEDOC, Chronic Diseases Research Center, Immunology, NOVA Medical School|FCM, Universidade Nova de Lisboa, Lisbon, Portugal

    Filipe Barcelos, Catarina Martins, Glória Nunes, Teresa Lopes & Luís-Miguel Borrego

  2. Departement of Rheumatology, Instituto Português de Reumatologia, Lisbon, Portugal

    Filipe Barcelos

  3. Department of Rheumatology, Hospital Cuf Descobertas, Lisbon, Portugal

    Filipe Barcelos & Jaime Branco

  4. CEAUL, Centro de Estatística e Aplicações, Universidade de Lisboa, Lisbon, Portugal

    Ana Papoila & Carlos Geraldes

  5. NOVA Medical School|FCM, Universidade Nova de Lisboa, Lisbon, Portugal

    Ana Papoila, Carlos Geraldes & Jaime Branco

  6. Department of Ophthalmology, Centro Hospitalar de Lisboa Central, Hospital de Santo António dos Capuchos, Lisbon, Portugal

    Joana Cardigos & Nuno Alves

  7. Department of Ophthalmology, Hospital Cuf Descobertas, Lisbon, Portugal

    Nuno Alves

  8. Department of Rheumatology, Instituto Português de Reumatologia, Lisbon, Portugal

    José Vaz-Patto

  9. Chronic Diseases Research Center, NOVA Medical School|FCM, Universidade Nova de Lisboa, Lisbon, Portugal

    Jaime Branco

  10. Department of Rheumatology, Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisbon, Portugal

    Jaime Branco

  11. Department of Immunoalergy, Hospital Cuf Descobertas, Lisbon, Portugal

    Luís-Miguel Borrego

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  1. Filipe Barcelos
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Contributions

FB conceived the original research idea, while all of the authors designed the study and created the study protocol. FB and JVP recruited the patients and collected the data. JC and NA recruited the healthy controls and collected the data. CM, GN and TL analyzed the blood samples using flow cytometry. CG and ALP performed the statistical analysis. JCB and LMB supervised all the work and the research protocol. All of the authors contributed to data analysis and interpretation. FB drafted the manuscript, and all of the authors revised it and contributed to it intellectually. All of the authors have approved the final version of the manuscript.

Corresponding author

Correspondence to Filipe Barcelos.

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The authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics committee of Hospital Cuf Descobertas, 8/09/2014, Ethics committee of Instituto Português de Reumatologia, 3/07/2015 and NOVA Medical School Ethics (no. 17/2016/CEFCM). All patients have signed an informed consent to participate according to the Declaration of Helsinki.

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Barcelos, F., Martins, C., Papoila, A. et al. Association between memory B-cells and clinical and immunological features of primary Sjögren’s syndrome and Sicca patients. Rheumatol Int 38, 1063–1073 (2018). https://doi.org/10.1007/s00296-018-4018-0

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