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J Autoimmun. 2016 Feb;67:102-110. doi: 10.1016/j.jaut.2015.11.002. Epub 2015 Dec 10.

Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren's syndrome.

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Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, Brest 29609, France; EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, Brest 29609, France.
Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes Cedex 01 44093, France.
Service de Médecine Interne, Hôpital Européen, Marseille, France.
Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille Cedex 59037, France.
Service de Rhumatologie, Hôpital Nord, CHU Amiens, Amiens 80054, France.
Service de Rhumatologie, CHRU de Rouen, Bois-Guillaume 76230, France.
EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France. Electronic address:



To determine whether B-cell markers (blood and minor salivary gland [SG] B-cell depletion [BCD], autoantibodies, B-cell-activating factor [BAFF]) are associated with clinical response to rituximab in patients with primary Sjögren's syndrome (pSS).


45 patients with pSS were included: in group I, 14 received low-dose rituximab (two 375-mg/m(2) infusions) in an open-labelled study; in group II, 17 received full-dose rituximab (two 1000-mg infusions) and 14 received a placebo in a randomized, controlled study. The proportion of SG B cells was assessed using pixel-based software analyses of digitized double-immunostained (CD3/CD20) whole SGs. Response was defined at week-24 according to the Sjögren's Syndrome Responder Index (SSRI)-30.


Response rate was 50% in both groups of rituximab-treated patients. Duration of blood BCD was similar in both groups despite the difference in rituximab dosage, and was highly correlated with residual serum-rituximab levels at week-16. SG B-cell dynamics mirrored blood B-cell levels, with a drastic decrease in SG B-cells at week-12 (group I), but an increase in ∼ 50% of patients in group II by week-24, in whom blood B cells had already returned. Duration of BCD was not associated with the clinical response, but responders had lower baseline proportions of SG B cells. Baseline serum BAFF level was correlated with the proportion of SG B-cells and other B-cell-activation markers, and was associated with the clinical response with higher levels in non-responders.


In pSS, half of the patients display an intense BAFF-driven B-cell activation and do not respond to a single course of rituximab.


B cells; BAFF; Histology; Primary; Rituximab; Sjögren's syndrome; Treatment efficacy

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