title: Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome.
abstract: Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0-10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus.
authors.affiliation: Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK.|Department of Rheumatology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Fisher
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.affiliation: Department of Orofacial Sciences, University of California San Francisco, San Francisco California, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Daniels
authors.affiliation: Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK.
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
authors.affiliation: Department of Pathology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brown
authors.affiliation: Department of Pathology, King's College London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Morgan
authors.affiliation: Rheumatology Unit, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.affiliation: Musculoskeletal Research Group and NIHR Biomedical Research Centre in Ageing and Chronic Diseases, Newcastle University, Newcastle, UK.
authors.forename: Wan-Fai
authors.initials: WF
authors.lastname: Ng
authors.affiliation: Department of Pathophysiology, University of Athens, Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Tzioufas
authors.affiliation: Section of Rheumatology, Casa di Cura di Lecco, Lecco, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Vitali
authors.affiliation: Department of Oral Medicine, King's College London, London, UK.
authors.forename: Pepe
authors.initials: P
authors.lastname: Shirlaw
authors.affiliation: Department of Pathology, University of Groningen, Groningen, The Netherlands.
authors.forename: Erlin
authors.initials: E
authors.lastname: Haacke
authors.affiliation: Department of Pathology, Brest University Hospital, Brest, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Costa
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, Groningen, The Netherlands.
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
authors.affiliation: Rheumatology Department, Cavale Blanche Hospital and Brest Occidentale University, ER129, Brest, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Devauchelle-Pensec
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Radstake
authors.affiliation: Rheumatology Department, Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, INSERM U1184, Le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Department of Oral Medicine, Dental Hospital, Birmingham, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Richards
authors.affiliation: Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Stack
authors.affiliation: Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK.|Department of Rheumatology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bowman
authors.affiliation: Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
mesh_terms: D001706:Biopsy; D003697:Delphi Technique; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008046:Lip; D008214:Lymphocytes / Q000473:pathology*; D012015:Reference Standards; D012470:Salivary Glands, Minor / Q000473:pathology*; D012793:Sialadenitis / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000473:pathology*
keywords: Autoimmunity; Outcomes research; Sjøgren's Syndrome