ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1488

Gene Expression Profile According To Systemic Disease Activity In Primary Sjögren’s Syndrome: Results From The Assessment Of Systemic Signs and Evolution Of Primary Sjögren’s Syndrome (ASSESS) Cohort

Nawal Rahal1, Nicolas Cagnard2, Ghada Alsaleh3, Raphaèle Seror4, Corinne Miceli-Richard5, Joelle Benessiano6, Philippe Dieude7, Jean Jacques Dubost8, Anne-Laure Fauchais9, Vincent Goeb10, Eric Hachulla11, Pierre-Yves Hatron12, C. Larroche13, Véronique le Guern14, Jacques Morel15, Aleth Perdriger16, Xavier Puechal17, Stephanie Rist18, Alain Saraux19, Damien Sene20, Jean Sibilia21, Olivier Vittecoq22, Philippe Ravaud23, Xavier Mariette24 and Jacques-Eric Gottenberg21, 1Strasbourg University Hospital, STRASBOURG, France, 2Institut Cochin, 75014 Paris, France, 3Univerity of Strasbourg, STRASBOURG, France, 4Rheumatology, Bicetre university hospital, LE Kremlin-Bicetre, France, 5Rheumatology Department, Université Paris-Sud 11, Bicêtre Hospital,, Kremlin Bicêtre, France, 6Rheumatology, Paris Unervisity Hospital BICHAT, Paris, France, 7Rheumatology, Rheumatology departement & INSERM U699, Paris Diderot university, APHP, Bichat hospital, Paris, France, 8Rheumatology, CHU G.-Montpied, Clermont-Ferrand, France, 9Department of Internal Medicine A, Dupuytren Hospital, Limoges University Hospital, Limoges, France, 10Rheumatology, Amiens University Hospital, Amiens, France, 11Internal Medicine, Lille CEDEX, France, 12Department of Internal Medicine, Claude Huriez University Hospital, Lille, France, 13Hospital University Bobigny, bobigny, France, 14Department of Internal Medicine, Hôpital Cochin, Paris, France, 15Montpellier University Hospital, Montpellier, France, 16Rheumatology, Hôpital Sud, Rennes, France, 17Department of Internal Medicine, Referral Center for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, 18Rheumatology, Orleans Hospital, Orleans, France, 19Rhumatologie, CHU de la Cavale Blanche, Brest Cedex, France, 20Internal Medicine, Hopital Lariboisière, Paris, France, 21Division of Rheumatology, University Hospital of Strasbourg, Strasbourg, France, 22Rheumatology, Rouen University Hospital & Inserm905, University of Rouen, Rouen Cedex, France, 23Epidemiology, Hopital Hotel Dieu, Paris Descartes University, Paris, France, 24Paris-Sud University, Paris, France

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Sjögren's Syndrome: Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

In primary Sjögren’s syndrome (pSS), the pathogenesis of systemic complications remains unclear. Only few gene expression studies were performed and concerned a limited number of patients, without any systemic complications. We therefore analyzed the gene profile of patients according to the international validated systemic disease activity score, the ESSDAI.

Methods:

The ASSESS cohort, a multicenter 5-year prospective cohort,  has been set up to identify predictive biomarkers of systemic complications in pSS. We selected 45 patients with high, moderate, or low systemic disease activity according to the ESSDAI. ARN extraction was performed from whole blood and was hybridized to Agilent 8x60K microarrays. 

Results:

41 patients were women, median age was 61 (25-80) years and median disease duration was 7 years. Median ESSDAI was 6 (0-31), 28 patients had at least one active domain and 18 patients had 2 or more active domains of the ESSDAI. The 45 patients were separated into 3 groups according to the ESSDAI: high  (H) (ESSDAI≥15, n= 16), moderate (M) (516 patients were treated with corticosteroids (2 in L, 3 in M, 11 in H; median dose: 5 mg/day (2-20 mg)), 14 with hydroxychloroquine (6/1/6 in L/M/H, respectively), and 6 with another immunosuppressant. Compared to patients in the L group, patients in the M group had 201 differentially expressed genes (DEG) and patients in the H group had 586 DEG. Most of the DEG belonged to various immune pathways involved in antigen presentation. The expression of BLK and EBF-1, 2 genes involved in B-cell activation and genetic predisposition to pSS, were significantly upregulated in H vs L patients.  79 interferon-regulated genes were differentially expressed, including 39 up- and 40 downregulated, in H vs L patients.  In addition, the gene expression profile of distinct systemic involvements only weakly overlapped. Thus, patients with articular involvement (n=5) had 400 DEG compared to those without, patients with lung involvement (n=9) had 305 DEG and patients with peripheral nervous system involvement (PNS, n=9) had 314 DEG. Only 11 genes were common between the list of DEG in articular and lung involvement, 10 were common between lung and PNS and 2 genes were common to the 3 lists.

Conclusion:

We identified different gene expression profiles according to the level of the ESDDAI and the nature of systemic involvement. Interestingly, systemic disease activity was not tightly associated with an interferon signature. This might be related to the study of peripheral blood, the effect of hydroxychloroquine and other immunosuppressants, or might suggest that systemic disease activity is not specifically driven by interferons in pSS.

Disclosure:

N. Rahal,
None;

N. Cagnard,
None;

G. Alsaleh,
None;

R. Seror,
None;

C. Miceli-Richard,
None;

J. Benessiano,
None;

P. Dieude,
None;

J. J. Dubost,
None;

A. L. Fauchais,
None;

V. Goeb,
None;

E. Hachulla,
None;

P. Y. Hatron,
None;

C. Larroche,
None;

V. le Guern,
None;

J. Morel,
None;

A. Perdriger,
None;

X. Puechal,
None;

S. Rist,
None;

A. Saraux,
None;

D. Sene,
None;

J. Sibilia,
None;

O. Vittecoq,
None;

P. Ravaud,
None;

X. Mariette,
None;

J. E. Gottenberg,
None.

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