Blood and Salivary Gland BAFF-Driven B-Cell Hyperactivity in Rituximab Non-Responder Patients with Primary Sjögren's Syndrome

Divi Cornec¹, Sebastian Costa², Valerie Devauchelle³, Sandrine Jousse-Joulin⁴, Pascale Marcorelles⁵, Jean-Marie Berthelot⁶, laurent chiche⁷, Eric Hachulla⁸, Pierre-Yves Hatron⁹, Vincent Goeb¹⁰, O Vittecoq¹¹, Alain Saraux¹² and Jacques-Olivier Pers¹³, ¹Department of rheumatology, Brest Occidentale University, Brest, France, ²anatomopathological department, Brest university hospital, Brest, France, ³Service de Rhumatologie, CHU Brest, Brest, France, ⁴Rheumatology, CHu La cavle Blanche, Brest, France, ⁵anatomopathological department, Brest university hospital, CHU Morvan, Brest, France, ⁶Rhumatologie, CHU Nantes, Nantes, France, ⁷internal medicine, Hopital Europeen, Marseille, France, ⁸Department of Internal Medicine, University Lille Nord-de-France, Lille, France, ⁹Service de Médecine Interne, Centre National de Référence des Maladies Systémiques Rares, Hôpital Claude Huriez, CHRU Lille, Lille, France, ¹⁰Rhumatologie, CHU Amiens, Amiens, France, ¹¹University Hospital, Rouen, France, ¹²Rheumatology Department, CHU de la Cavale Blanche, Brest Cedex, France, ¹³EA2216/ERI29 UBO, Brest, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Sjogren's syndrome and rituximab

Session Information

Date: Tuesday, November 10, 2015

Title: Sjögren's Syndrome: Translational Insights into Sjögren's Syndrome

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: To determine whether B-cell markers (blood and minor salivary gland (SG) B-cell depletion (BCD), autoantibodies, BAFF) are associated with clinical response to rituximab in patients with primary Sjögren’s syndrome (pSS).

Methods: 45 pSS patients were included: 14 who received low-dose rituximab (two 375 mg/m² infusions) in an open-labelled study (group I); and 17 who received full-dose rituximab (two 1000 mg infusions) from a randomized-controlled study (group II), as well as their 14 placebo. SG B-cell proportion was assessed using a pixel-based software analysis of digitized double-immunostained (CD3/CD20) whole SG slides. Response was defined at W24 according to the Sjögren’s Syndrome Responder Index (SSRI)-30.

Results: Response rate was 50% in both groups of rituximab-treated patients. Duration of blood BCD was similar in the 2 groups despite the difference in rituximab dosage, and was highly correlated with residual serum rituximab levels as lately as W16. SG B-cell dynamics mirrored blood B-cell levels, with a drastic SG B-cell proportion decrease at W12 (group I), but an increase at W24 in half of the patients from group II who had already experienced blood B-cell return. Duration of BCD was not associated with the clinical response, but responders had lower baseline SG B-cell proportion. Baseline serum BAFF level correlated with SG B-cell proportion, as well as with other B-cell activation markers (serum free-light chains, serum IgG, beta-2 microglobulin, or auto-antibody levels). This global B-cell hyperactivation was associated with the clinical response, with higher serum BAFF levels in non-responders.

Conclusion: In pSS patients, intense BAFF-driven B-cell activation is associated with nonresponse to a single rituximab course.

Disclosure: D. Cornec, None; S. Costa, None; V. Devauchelle, None; S. Jousse-Joulin, None; P. Marcorelles, None; J. M. Berthelot, None; L. chiche, None; E. Hachulla, None; P. Y. Hatron, None; V. Goeb, None; O. Vittecoq, None; A. Saraux, None; J. O. Pers, None.

To cite this abstract in AMA style:

Cornec D, Costa S, Devauchelle V, Jousse-Joulin S, Marcorelles P, Berthelot JM, chiche L, Hachulla E, Hatron PY, Goeb V, Vittecoq O, Saraux A, Pers JO. Blood and Salivary Gland BAFF-Driven B-Cell Hyperactivity in Rituximab Non-Responder Patients with Primary Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/blood-and-salivary-gland-baff-driven-b-cell-hyperactivity-in-rituximab-non-responder-patients-with-primary-sjogrens-syndrome/. Accessed .

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