title: Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren's syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Divi
authors.initials: D
authors.lastname: Cornec
authors.affiliation: Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, Brest 29609, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Costa
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle-Pensec
authors.affiliation: 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.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jousse-Joulin
authors.affiliation: Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, Brest 29609, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.affiliation: Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes Cedex 01 44093, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.affiliation: Service de Médecine Interne, Hôpital Européen, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chiche
authors.affiliation: Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille Cedex 59037, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille Cedex 59037, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hatron
authors.affiliation: Service de Rhumatologie, Hôpital Nord, CHU Amiens, Amiens 80054, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goeb
authors.affiliation: Service de Rhumatologie, CHRU de Rouen, Bois-Guillaume 76230, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vittecoq
authors.affiliation: 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.
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
authors.affiliation: 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.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
mesh_terms: D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D000069283:Rituximab
keywords: B cells; BAFF; Histology; Primary; Rituximab; Sjögren's syndrome; Treatment efficacy