Towards personalised treatment in primary Sjogren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment

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Abstract

Objectives The aims of this study were (1) to assess the effect of rituximab (RTX; anti-CD20) treatment in patients with primary Sjogren's syndrome (pSS) based on sequential parotid biopsies obtained in a placebo-controlled, randomised clinical trial, and (2) to assess the prognostic value of the histological characteristics of parotid gland tissue with regard to responsiveness to RTX treatment.

Methods In a double-blinded, placebo-controlled trial, sequential parotid gland biopsies were taken from 20 RTX-treated and 10 placebo-treated patients with pSS, at baseline and 12 weeks after treatment. The relative amount of lymphocytic infiltrate (stained for CD45), absolute number of T cells and B cells per mm(2) parenchyma (stained for CD3 and CD20, respectively), focus score, number of germinal centres and of lymphoepithelial lesions per mm(2) in parotid gland parenchyma were assessed. Histopathological data were compared between clinical responders (decrease in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) score of >= 3 at 12 weeks compared with baseline) and non-responders (change in ESSDAI

Results In RTX-treated patients, a significant reduction in the number of CD20+ B cells/mm(2) parenchyma was observed, while no such reduction was observed in placebo-treated patients. The number of CD3+ T cells/mm(2) in parenchyma did not change in either group. Furthermore, the number and the severity of lymphoepithelial lesions/mm(2) and number of germinal centres/mm(2) was significantly reduced in RTX-treated patients, but did not change in placebo-treated patients. When comparing the pretreatment characteristics of clinical responders with non-responders, the median number of CD20+ B cells/mm(2) parenchyma at baseline was significantly higher in responders (1871 vs 353 cells/mm(2), p

Conclusions RTX treatment in pSS leads to a major reduction of lymphocytic infiltration and to fewer B cells, germinal centres and lymphoepithelial lesions in parotid gland parenchyma. A high pretreatment number of CD20+ B cells/mm(2) parotid gland parenchyma predicts better responsiveness of patients with pSS to RTX treatment. Pretreatment parotid gland histopathological characteristics could therefore contribute to a more personalised treatment approach to pSS.

Original languageEnglish
Pages (from-to)1933-1938
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume75
Issue number11
DOIs
Publication statusPublished - Nov-2016

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