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Abstract Number: 521

CXCL13 Serum Levels Is Associated with Lymphoma, High B Cells Markers and Diseases activity  in Primary Sjögren ’s Syndrome Patients

Gaetane Nocturne1, Olivier Fogel2, Philippe Dieude3, Jean Jacques Dubost4, Anne-Laure Fauchais5, Vincent Goeb6, Eric Hachulla7, Claire Larroche8, Véronique Le Guern9, Jacques Morel10, Aleth Perdriger11, Xavier Puéchal12, Stephanie Rist Bouillon13, Valerie Devauchelle14, Damien Sène15, O Vittecoq16, Corinne Miceli-Richard17, Jacques Gottenberg18 and Xavier Mariette19, 1INSERM U1012, Paris sud university, Le Kremlin Bicetre, France, 2INSERM U1012, Paris sud university, Le Kremlin Bicêtre, France, 3Rhumatologie, Hopital Bichat Claude Bernard, Paris, France, 4Rheumatology, CHU G.-Montpied, Clermont-Ferrand, France, 5Department of Internal Medicine A, Dupuytren Hospital, Limoges University Hospital, Limoges, France, 6Rhumatology Department, University Hospital, AMIENS, France, 7Faculté de Médecine Henri Warembourg, Université Lille Nord de France, Lille, France, 8Internal Medicine, Avicenne Hospital,, Assistance Publique des Hôpitaux de Paris,, Bobigny, France, 9Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, Paris, France, 10Department of Rheumatology, Hôpital Lapeyronie, Montpellier, France, 11Rhumatologie, Rennes, France, 12National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, Paris, France, 13Rhumatologie, Hopital La Source, La Source, France, 14Rheumatology, Brest university medical school, EA 2216, Lab Ex, INSERM, IGO,UBO and CHU de la Cavale Blanche,, Brest, France, 15Hopital Lariboisière, service de Médecine Interne, Paris, France, 16Rouen University Hospital & Inserm U905, Rouen, France, 17Rheumatology Department, Université Paris-Sud 11, Bicêtre Hospital,, Kremlin Bicêtre, France, 18Rheumatology, Strasbourg University Hospital, Strasbourg, France, 19rheumatology, Université Paris-Sud, Le Kremlin Bicêtre, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: chemokines and pathogenesis, Sjogren's syndrome

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Session Information

Session Title: Sjogren's Syndrome: Pathophysiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: Development of non-Hodgkin lymphoma (NHL) is one of the most severe complications associated with pSS. It affects 5-10% of the patients. Definition of predictive factors is mandatory to enable a more individualized approach. CXCL13 is a chemokine also known as B lymphocyte chemo-attractant (BLC) involved in the homing of B cells within germinal centers. High CXCL13 serum levels have been shown to be predictive of NHL occurrence in the general population outside the context of autoimmunity [1]. Given this association with NHL in the general population, we decided to assess a possible association between CXCL13 serum levels and lymphoma and B-cell biomarkers in our cohort of pSS patient.

Methods: CXCL13 serum levels at inclusion were evaluated in 385 pSS patients included in the ASSESS cohort by multiplex assay. Among them, 21 patients had a NHL (history of or future). Levels of CXCL13 were compared in the different subsets of patients with a Mann-Whitney test. Association between CXCL13 levels and B cells markers was assessed by the Pearson’s r correlation test.

Results: The median [range] levels of CXCL13 was 108 [6.33-4040] pg/ml in the 385 pSS patients from the ASSESS cohort. We found an increased CXCL13 serum level in pSS patients with NHL vs pSS patients without NHL (191.1 [43.7-3251] vs 105 [6.33-4040], p=0.008). CXCL13 was also increased in patients with active disease (ESSDAI ≥5) compared to patients with inactive disease (ESSDAI < 5) (98.5 [6.3-3251] vs 66.9 [11.1-4040], p=0.009). Last we found significant correlations between CXCL13 serum levels and B cells biomarkers such as gammaglobulinemia (r=0.11, p=0.04), β2-microglobulin level (r=0.22, p< 0.0001), BAFF serum level (r=0.18, p=0.0006), free light chain kappa/lambda ratio (r=0.21, p<0.0001) and rheumatoid factor titer (r=0.22, p<0.0001) and an increased level in patients with anti-SSA vs patients without ( 138.3 [7.2-4040] vs 76.5 [6.3-1515], p<0.0001).

Conclusion: This study demonstrates that CXCL13 may be involved in lymphomagenesis in pSS patients. We demonstrated that CXCL13 serum level is increased in pSS patients with NHL, in patients with active disease and is associated with B cells markers. Further studies will be needed to investigate the functional role of this chemokine in the disease.

Reference: 1. Purdue et al. Blood, 2014


Disclosure:

G. Nocturne,
None;

O. Fogel,
None;

P. Dieude,
None;

J. J. Dubost,
None;

A. L. Fauchais,
None;

V. Goeb,
None;

E. Hachulla,
None;

C. Larroche,
None;

V. Le Guern,
None;

J. Morel,
None;

A. Perdriger,
None;

X. Puéchal,
None;

S. Rist Bouillon,
None;

V. Devauchelle,
None;

D. Sène,
None;

O. Vittecoq,
None;

C. Miceli-Richard,
None;

J. Gottenberg,
None;

X. Mariette,
None.

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