Specific T Cell and B Cell Distributions Characterize Subgroups of Patients with Primary Sjögren's Syndrome and Are Associated with Disease Activity and Pro-Inflammatory Cytokine Expression

Lucas Le Lann¹, Quentin Simon¹, Christophe Jamin¹, Maria Orietta Borghi², Lorenzo Beretta³, Ricard Cervera⁴, Alain Saraux⁵, Divi Cornec¹, Rik Lories⁶, Carlo Chizzolini⁷, Marta E. Alarcon Riquelme⁸, Jacques-Olivier Pers¹ and on behalf of the PRECISESADS Consortium, ¹INSERM ERI29, EA2216, Université de Brest, Labex IGO, CHRU Morvan, Brest, France, ²University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy, ³Rheumatology, Milan, Italy, ⁴Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic de Barcelona, Barcelona, Spain, ⁵Rheumatology Department, CHU de la Cavale Blanche, Brest Cedex, France, ⁶Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven and University Hospitals Leuven., Leuven, Belgium, ⁷University hospital of Geneva, Geneva, Switzerland, ⁸Centro de Genomica e Investigación Oncológica, Pfizer-University of Granada-Junta de Andalucía, Granada, Spain

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: cytokines and flow cytometry, Disease Activity, Sjogren's syndrome

Session Information

Date: Wednesday, November 16, 2016

Title: Sjögren's Syndrome II: Basic Insights

Session Type: ACR Concurrent Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose : The goal of the IMI PRECISESADS project is to reclassify individuals affected by systemic autoimmune diseases (SADs) into clusters of molecular, instead of clinical entities. In this project, we investigated 40 individuals with primary Sjögren’s syndrome (pSS), as diagnosed by the revised American-European classification criteria (3 men and 37 women, mean age: 56.3±12.3 years). and 53 healthy controls (HCs) (11 men and 42 women, mean age: 44.1±12.1 years) to determine whether a fine flow cytometry analysis of T and B cell distribution in whole blood could cluster individuals according to disease activity.

Methods: Two flow cytometry panels were designed. The first panel was dedicated to T cells and combined FITC-CD57, PE-CD45RA, PC7-CD62L, PC5.5-CD27, APC-CD38, AAF750-CD3, PB-CD4,KO-CD8 mAbs. The second panel was dedicated to B cells and combined FITC-IgD, PE-TACI, KO-CD5, PC7-CD24, PC5.5-CD27, PB-CD38, APC-CD19, AAF750-CD11b mAbs. Disease activity was determined according to ESSDAI. A Luminex-based system was used to analyze up to 88 cytokines, chemokines and soluble factors in serum of pSS patients and HCs.

Results: A combined analysis of T and B cell distribution highlighted two groups of individuals with a strong cluster of pSS patients in one of them. Indeed, the first cluster (group A) gathers together 24 pSS patients and 5 HCs while group B consists in 16 pSS patients and 49 HCs. Group A was characterized by the association of an increase of activated naïve B cells (IgD⁺ CD24⁺ CD38⁺ CD27^–), a decrease of memory B cells (IgD^– CD38^– CD27⁺), an increase of central memory CD4⁺ T cells (CD45RA^– CD62L⁺ CD27⁺), an increase of effector memory CD8⁺ T cells (CD45RA^– CD62L^– CD27^–) and a decrease of central memory CD8⁺ T cells (CD45RA^– CD62L⁺ CD27⁺) compared to group B and 91% of HCs. Interestingly, group A patients have a higher disease activity score when compared to group B (Mean ESSDAI score 5.0±1.9 versus 3.2±0.9 respectively). Finally, serum pro-inflammatory molecules (interleukin (IL)-6, C-reactive protein (CRP), Chemokine (C-C motif) ligand 20 (CCL20), CCL3, matrix metalloproteinase-7 (MMP-7), IL-18) were markedly up-regulated in group A patients compared to HCs and group B patients (See heat-map below).

Heat-map shows mean-ratio of pro-inflammatory molecule concentrations relative to HCs in each group of pSS patients.

Conclusion: A fine flow cytometry analysis of T and B cell subsets characterizes pSS patients with a higher disease activity score and a pro-inflammatory signature. Similar approaches are ongoing in the context of the PRECISESADS project for other SADs.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n° 115565.www.precisesads.eu

Disclosure: L. Le Lann, None; Q. Simon, None; C. Jamin, None; M. O. Borghi, None; L. Beretta, None; R. Cervera, None; A. Saraux, None; D. Cornec, None; R. Lories, None; C. Chizzolini, None; M. E. Alarcon Riquelme, None; J. O. Pers, None.

To cite this abstract in AMA style:

Le Lann L, Simon Q, Jamin C, Borghi MO, Beretta L, Cervera R, Saraux A, Cornec D, Lories R, Chizzolini C, Alarcon Riquelme ME, Pers JO. Specific T Cell and B Cell Distributions Characterize Subgroups of Patients with Primary Sjögren’s Syndrome and Are Associated with Disease Activity and Pro-Inflammatory Cytokine Expression [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/specific-t-cell-and-b-cell-distributions-characterize-subgroups-of-patients-with-primary-sjogrens-syndrome-and-are-associated-with-disease-activity-and-pro-inflammatory-cytokine-expression/. Accessed .

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