title: Is minor salivary gland biopsy more than a diagnostic tool in primary Sjögren׳s syndrome? Association between clinical, histopathological, and molecular features: a retrospective study.
abstract: OBJECTIVE
  Several histological scoring systems, including the focus score, performed in minor salivary glands (MSGs) by hematoxylin-eosin (H&E) staining, have been employed in clinical practice to assess the inflammatory infiltrate and provide the diagnosis of primary Sjo¨gren׳s syndrome (pSS). Aims of this study were to integrate different scoring systems and identify potential differences in the molecular profile of lymphoid cytokines related to germinal center (GC) formation and clinical subsets in pSS.
  
  
  METHODS
  Overall, 104 pSS patients and 40 subjects with sicca non-pSS were retrospectively evaluated. MSG biopsies were evaluated by H&E and immunofluorescence to assess histological pattern, Chisholm and Mason grading system, Tarpley score, a grading for the severity of inflammatory infiltrate, T-/B-cell segregation, and the presence of GC. MSGs from 50 pSS patients and 30 sicca non-pSS patients were processed by real-time PCR to assess LTα, LTβ, BAFF, CXCR4, CXCL12, CXCR5, CXCL13, CCR7, CCL19, and CCL21.
  
  
  RESULTS
  GCs presence was associated with anti-Ro/SSA and anti-La/SSB antibodies, hypergammaglobulinemia, salivary gland swelling, higher Tarpley score and focus score, and extraglandular involvement but, at multivariate analysis, only extraglandular involvement was independently associated to GC. pSS patients displayed higher level of all cytokines compared to those with sicca symptoms. GC(+) pSS patients displayed higher level of all cytokines compared to those GC(-).
  
  
  CONCLUSIONS
  Our study demonstrates that different histopathological patterns, including GC presence, reflect different cytokine expression and different clinical subsets. We believe that the combined immunofluorescence/molecular approach in MSGs would help to tailor diagnostic and therapeutic approach for different subsets of pSS patients.
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy. Electronic address: francescocarubbi@libero.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carubbi
authors.affiliation: Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Alunno
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Benedetto
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruscitti
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
authors.forename: Onorina
authors.initials: O
authors.lastname: Berardicurti
authors.affiliation: Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bartoloni
authors.affiliation: Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
authors.forename: Onelia
authors.initials: O
authors.lastname: Bistoni
authors.affiliation: Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caterbi
authors.affiliation: Division and Laboratory of Rheumatology, University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Division and Laboratory of Rheumatology, University of Palermo, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
authors.affiliation: Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.affiliation: Department of Clinical Science and Biotechnology, Rheumatology Unit, University of L׳Aquila, L׳Aquila 67100, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012470:Salivary Glands, Minor / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: BAFF; CCL19; CCL21; CCR7; CXCL12; CXCL13; CXCR4; CXCR5; Germinal center; LTα; LTβ; Minor salivary glands; Sjo¨gren׳s syndrome