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

Objective Murine models (MRL/gld/gld mice) and recent evidence in humans suggest a po ssible role of Fas and Fas ligand (Fas-L) germline mutations in the pathoge nesis of autoimmune-related lymphoproliferation, including adult cases. In this study, the presence of Fas and Fas-L germline mutations was investigat ed in a consecutive series of adult patients with lymphoproliferative disor ders occurring in the context of Sjogren'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.) we re investigated. All patients were suffering from atypical lymphoproliferat ive disorders or MALT lymphoproliferative lesions (mean duration 3.5 yrs.). Four patients later developed a malignant lymphoma. DNA from peripheral bl ood mononuclear cells from II patients and 10 controls was tested for germl ine 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 (SSC P) method. Results All DNA samples from both patients and controls showed amplification of Fas and Fas-L specific fragments. Identical SSCP migration patterns were obser ved 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 presen t in exons different from those analyzed our data do not support the hypoth esis that germline mutations in these genes are responsible for a major sub set of lymphoproliferative syndromes in adult patients with SS and type II MC. Additional studies would be worthwhile in SLE-related lymphoproliferati on, which is, however, a subset of limited clinical relevance when consider ing all cases with autoimmune-related lymphoproliferation.