Lack of Fas and Fas-L mutations in patients with lymphoproliferative disorders associated with Sjögren's syndrome and type II mixed cryoglobulinemia

Clin Exp Rheumatol. May-Jun 1999;17(3):339-42.


Objective: Murine models (MRL/gld/gld mice) and recent evidence in humans suggest a possible role of Fas and Fas ligand (Fas-L) germline mutations in the pathogenesis of autoimmune-related lymphoproliferation, including adult cases. In this study, the presence of Fas and Fas-L germline mutations was investigated in a consecutive series of adult patients with lymphoproliferative disorders occurring in the context of Sjögren's syndrome (SS) and type II mixed cryoglobulinemia (MC).

Methods: 11 patients (8 primary SS and 3 type II MC; F/M: 10/1; mean age 64 yrs.) were investigated. All patients were suffering from atypical lymphoproliferative disorders or MALT lymphoproliferative lesions (mean duration 3.5 yrs.). Four patients later developed a malignant lymphoma. DNA from peripheral blood mononuclear cells from 11 patients and 10 controls was tested for germline mutations in the Fas gene (exons 4, 8 and 9) and Fas-L gene (exon 4) by the polymerase chain reaction-single strand conformation polymorphism (SSCP) method.

Results: All DNA samples from both patients and controls showed amplification of Fas and Fas-L specific fragments. Identical SSCP migration patterns were observed in all the cases, indicating the lack of mutations in the whole series.

Conclusion: Although it cannot be excluded that Fas and Fas-L mutations might be present in exons different from those analyzed, our data do not support the hypothesis that germline mutations in these genes are responsible for a major subset of lymphoproliferative syndromes in adult patients with SS and type II MC. Additional studies would be worthwhile in SLE-related lymphoproliferation, which is, however, a subset of limited clinical relevance when considering all cases with autoimmune-related lymphoproliferation.

MeSH terms

  • Aged
  • Cryoglobulinemia / blood
  • Cryoglobulinemia / complications*
  • Cryoglobulinemia / genetics*
  • DNA Mutational Analysis
  • Fas Ligand Protein
  • Female
  • Gene Amplification
  • Germ-Line Mutation
  • Humans
  • Leukocytes, Mononuclear
  • Lymphoma / complications
  • Lymphoma / genetics
  • Lymphoproliferative Disorders / blood
  • Lymphoproliferative Disorders / complications*
  • Lymphoproliferative Disorders / genetics*
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / complications*
  • Sjogren's Syndrome / genetics*
  • fas Receptor / blood
  • fas Receptor / genetics*


  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • fas Receptor