title: Stereotypic rheumatoid factors that are frequently expressed in mucosa-associated lymphoid tissue-type lymphomas are rare in the labial salivary glands of patients with Sjögren's syndrome.
abstract: OBJECTIVE
  Among autoimmune diseases, Sjögren's syndrome (SS) is most strongly associated with the development of malignant B cell lymphoma, in particular mucosa-associated lymphoid tissue (MALT)-type lymphoma. Previously, we have shown that in ∼40% of cases of salivary gland MALT lymphoma, high-affinity stereotypic rheumatoid factor (RF) B cell receptors, specific for IgG-Fc, are expressed. This study was undertaken to investigate whether in the inflamed salivary glands of patients with SS, a similar RF-biased Ig repertoire is present.
  
  
  METHODS
  Extensive analyses of the B cell Ig VH region repertoire were performed on microdissected tissue samples from the labial salivary glands of 4 patients with SS.
  
  
  RESULTS
  All SS labial salivary glands harbored expanded B cell clones, of which 1 or 2 were highly expanded and detected in >50% of the microdissected samples. However, among the identified 464 distinct Ig clonotypes, only 3 stereotypic RF-expressing clones were detected. In 2 patients with SS, an RF-expressing clone was detected at low frequency in 1 of the microdissected samples, whereas 1 patient with SS harbored a highly expanded RF-expressing clone that was detected in all microdissected samples and also detected in the peripheral blood. Two years after analysis of this sample, the latter patient developed a diffuse large B cell lymphoma originating from the same RF clone.
  
  
  CONCLUSIONS
  Inflamed labial salivary glands in patients with SS generally harbor 1 or 2 highly expanded B cell clones. The repertoire strongly biased toward stereotypic RFs in salivary gland MALT lymphomas is not a reflection of a similar repertoire in the inflamed salivary glands of patients with SS; rather, in the latter, the repertoire is based on a strong selection advantage of incidental stereotypic RF-expressing B cells.
authors.affiliation: Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bende
authors.forename: Linda M
authors.initials: LM
authors.lastname: Slot
authors.forename: Robbert
authors.initials: R
authors.lastname: Hoogeboom
authors.forename: Thera A M
authors.initials: TA
authors.lastname: Wormhoudt
authors.forename: Akanbi O
authors.initials: AO
authors.lastname: Adeoye
authors.forename: Jeroen E J
authors.initials: JE
authors.lastname: Guikema
authors.forename: Carel J M
authors.initials: CJ
authors.lastname: van Noesel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D012217:Rheumatoid Factor / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D012217:Rheumatoid Factor