Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Serum IL-21 Is Increased and Associated with Higher Disease Activity and Higher Serum Levels of Markers of B-Cell Activation in Primary Sjgren's Syndrome.

Gottenberg1,  Jacques-Eric, Alsaleh1,  Ghada, Miceli-Richard2,  Corinne, Seror3,  Raphaèle, Benessiano4,  Joelle, Devauchelle-Pensec5,  Valerie, Dieude6,  Philippe

Strasbourg University Hospital, Strasbourg, France
Internal Medicine, Lille CEDEX, France
Service de médecine interne, Hôpital Claude Huriez, Université Lille II, Lille, France, Paris, France
Hospital University Bobigny, France
Cochin Hospital, Paris, France
Hopital Lapeyronie, Montpellier, France
Hôpital Sud, Rennes, France
Le Mans General Hospital, Le Mans, France
Hospital University Orléans, France
CHU de la Cavale Blanche, Brest Cedex, France
Pitie-Salpetriere Hospital, Paris, France
Hopital Bicêtre, Le Kremlin Bicêtre, France
Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Strasbourg, France
Nihon Univ Hikarigoaka Hosp, Nerima-ku Tokyo, Japan
Hopital Hotel Dieu, Paris Descartes University, Paris, France
Université Paris-Sud, Le Kremlin Bicetre, France
Bicetre university hospital, LE Kremlin-Bicetre, France
Rheumatology, Paris Unervisity Hospital BICHAT, France
Brest Occidentale university, Brest, France
APHP, Hopital Bichat, Paris, France
CHU Gabriel Montpied, Clermont-Ferrand, France
Hospital, Limoges, France
Rheumatology, Rouen Unervisity Hospital, France, France

Background/Purpose:

Recent data from animal models and patients with primary Sjögren's syndrome (pSS) suggest that follicular T helper cells (Tfh), which secrete predominantly IL-21, might contribute to the marked B-cell activation observed in pSS. We aimed to investigate serum IL-21 level and its correlation with autoantibody secretion, markers of B-cell activation and disease activity in pSS

Methods:

400 patients with pSS have been included in the 5-year prospective multicenter ASSESS cohort (Assessment of SyStemic features and Evolution of primary Sjögren's Syndrome) since 2006. Clinical data and disease activity using the ESSDAI score have been collected homogeneously. DNA, RNA and serum were collected at inclusion and immediately frozen. Central assessment of serum IL-21 was performed using Ebioscience assay. IL-21 and IL-21R gene polymorphism (rs2221903, rs3093301, rs907715 were genoyped.

Results:

Serum IL-21, assessed in 331 patients, was significantly higher in pSS (median: 342 pg/ml, 25th–75th: 181–588) than in healthy controls (82 [55–118] pg/ml, P< 0.0001 ). Patients with either anti-SSA or anti-SSA and SSB antibodies had more frequently detectable IL-21 than patients without anti-SSA nor anti-SSB antibodies (94.9% vs 87.0%, P= 0.02). Serum IL-21 was correlated with IgG (r=0.24, P< 0.0001), kappa (r= 0.11, P= 0.04) and lambda (r= 0.15, P= 0.006) free light chains of immunoglobulins, but not with BAFF or beta2-microglobulin. No association was found between IL-21 or IL-21 gene polymorphisms and serum IL-21 level. IL21 was significantly correlated with systemic disease activity assessed by the ESSDAI (r=0.2, P= 0.0009). In patients with marked systemic disease activity (ESSDAI equal or superior to 7 corresponding to the 75th value of ESSDAI scores of all the patients), serum IL-21 was significantly increased (median 512.6 vs 329.9 pg/ml in patients with ESSDAI<7, P= 0.009).

Conclusion:

Serum IL-21 level is increased in pSS. This increase is not determined by the assessed gene polymorphisms. The increase of IL-21 is associated with increased systemic disease activity and marked B-cell activation. Targeting IL-21 or follicular T helper cells might therefore represent a promising therapeutic perspective in pSS.

To cite this abstract, please use the following information:
Gottenberg, Jacques-Eric, Alsaleh, Ghada, Miceli-Richard, Corinne, Seror, Raphaèle, Benessiano, Joelle, Devauchelle-Pensec, Valerie, et al; Serum IL-21 Is Increased and Associated with Higher Disease Activity and Higher Serum Levels of Markers of B-Cell Activation in Primary Sjgren's Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :488
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