title: BLyS upregulation in Sjogren's syndrome associated with lymphoproliferative disorders, higher ESSDAI score and B-cell clonal expansion in the salivary glands.
abstract: OBJECTIVE
  Primary SS is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels in SS-related B-cell lymphoproliferative disorders were studied by integrating the results with the disease activity score and with molecular analyses of B-cell expansion in the salivary glands.
  
  
  METHODS
  Seventy-six primary SS patients (with or without lymphoma or prelymphomatous manifestations), 56 HCV-related cryoglobulinaemic vasculitis patients and 55 controls were studied. s-BLyS and molecular analyses of B-cell expansion in the salivary gland tissues were performed. Patients with SS and persistent parotid swelling underwent parotid biopsy.
  
  
  RESULTS
  s-BLyS differed between SS subgroups, higher levels being documented in patients with lymphoma or prelymphomatous manifestations vs SS without [1.85 (0.45-4.12) ng/ml vs 1.12 (0.56-1.98) ng/ml; P < 0.0001]. s-BLyS levels significantly correlated with the European League Against Rheumatism (EULAR) SS disease activity index (r = 0.62, P < 0.0001, Spearman's test). Clonal B-cell expansion in the salivary glands, but not polyclonal B-cell expansion, was associated with higher s-BLyS levels [1.98 (0.45-4.12) ng/ml vs 1.15 (0.56-3.25) ng/ml; P = 0.013)].
  
  
  CONCLUSIONS
  Higher s-BLyS levels and tissue clonal B-cell expansion characterize SS with B-cell lymphoproliferative disorders, even at prelymphomatous stages. This subgroup of SS patients showed the highest EULAR SS disease activity index scores. This represents a biologic rationale for targeting both clonal B-cell expansion and s-BLyS overproduction in SS.
authors.affiliation: Rheumatology Clinic, Department of Medical and Biological Sciences, University Hospital Santa Maria della Misericordia, Udine, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Quartuccio
authors.forename: Sara
authors.initials: S
authors.lastname: Salvin
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Marta
authors.initials: M
authors.lastname: Maset
authors.forename: Elena
authors.initials: E
authors.lastname: Pontarini
authors.forename: Miriam
authors.initials: M
authors.lastname: Isola
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
mesh_terms: D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D001706:Biopsy; D016022:Case-Control Studies; D049109:Cell Proliferation; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012469:Salivary Glands / Q000276:immunology*; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000097:blood*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D053264:B-Cell Activating Factor