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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.

Author information

1
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.
2
Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, Brest 29609, France.
3
Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes Cedex 01 44093, France.
4
Service de Médecine Interne, Hôpital Européen, Marseille, France.
5
Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille Cedex 59037, France.
6
Service de Rhumatologie, Hôpital Nord, CHU Amiens, Amiens 80054, France.
7
Service de Rhumatologie, CHRU de Rouen, Bois-Guillaume 76230, France.
8
EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France. Electronic address: pers@univ-brest.fr.

Abstract

OBJECTIVES:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

KEYWORDS:

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

PMID:
26688003
DOI:
10.1016/j.jaut.2015.11.002
[Indexed for MEDLINE]

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