A review of salivary gland histopathology in primary Sjögren’s syndrome with a focus on its potential as a clinical trials biomarker

Abstract

Salivary gland changes, characterised by a focal lymphocytic sialadenitits, play an important role in the diagnosis of primary Sjögren's syndrome (PSS) and were first described over 40 years ago. Recent evidence suggests that minor salivary gland biopsy may also provide information useful for prognostication and stratification, yet difficulties may arise in the histopathological interpretation and scoring, and evidence exists that reporting is variable. With the increasing number of actual and proposed clinical trials in PSS, we review the evidence that might support the role of histopathology as a biomarker for stratification and response to therapy and highlight areas where further validation work is required.

Need for consensus guidelines to standardise the assessment of germinal centres and other histopathological parameters in salivary gland tissue of patients with primary Sjögren's syndrome

“…We fully agree with van Roon et al 1 and other authors about the need for consensus guidelines to standardise the histopathological evaluation of salivary gland biopsies in patients with pSS 3. A standardised scoring system may facilitate prognostication and stratification of patients with pSS and is needed for a valid evaluation of various clinical trials 3.…”

“…A standardised scoring system may facilitate prognostication and stratification of patients with pSS and is needed for a valid evaluation of various clinical trials 3. In particular, histological definition of GCs in salivary gland tissue is warranted, since these structures can be difficult to detect in diagnostic H&E-stained tissue sections.…”

BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation

“…The histological hallmark of the disease is a multifocal nodular immune infiltration of the exocrine glands, predominantly composed of CD4 + T and B lymphocytes, but also CD8 + T cells and long-lived plasma cells [2][3][4]. In addition, ectopic germinal center (GC)-like structures were observed in 10 to 30% of patients [2,5]; their presence was associated with autoantibody seropositivity, disease activity, and higher risk of developing lymphoma [2,[5][6][7]. B cells within ectopic GCs undergo antigendriven expansion and somatic hypermutation followed by selection [6].…”

Do high numbers of salivary gland-infiltrating B cells predict better or worse outcomes after rituximab in patients with primary Sjögren's syndrome?

“…This debate is important and timely, since, besides its indisputable diagnostic value,3 salivary gland histopathology is increasingly considered to be a useful tool to assess the effects of treatments in clinical trials 4 5. Furthermore, despite promising open-labelled studies and two small randomised trials,6 the two large randomised controlled trials TEARS7 and TRACTISS8 (main results of which were revealed at the 2015 American College of Rheumatology meeting) did not demonstrate the superiority of rituximab over placebo on their primary end points.…”