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Sjögren's syndrome (SS): are increased serum levels of cytokine FMS-like tyrosine kinase 3 ligand (Flt3L) indicative of lymphoma?
  1. G J Tobón,
  2. V Devauchelle,
  3. P Youinou,
  4. J-O Pers
  1. EA 2216 ‘Immunologie et Pathologie’ and IFR 148 ScInBioS, Université de Brest, and Université Européenne de Bretagne, Brest, France

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Background

Flt3L, which is involved in the ontogenesis of B cells (particularly in their malignant proliferation in pSS) might contribute to the absolute excess of activated Bm2/germinal centre funder Bm2' B lymphocytes which characterises the peripheral blood (PB) pattern of these patients.

Objectives

Our aims were threefold: (1) Compare the serum levels of FL of 64 Sjögren's syndrome (SS) patients with those of 20 healthy controls (HCs). (2) Quantify B cell expression of this ligand and its receptor Flt3 in the PB and the salivary glands (SGs) of patients. (3) And evaluate the effect of FL-treated B cells on SGs by co-culture of these circulating B cells with human SG (HSG) epithelial cell line cells.

Results

(1) There were more serum FL in SS patients that in HCs (135.8±5.5 vs 64.4±4.5 pg/ml, p<0.001), their levels correlated with the clinical activity of the disease and with the proportions of Bm2/Bm2′ in the PB (r=50, p<0.001). (2) Furthermore, Flt3 was selectively expressed in these circulating B cell subsets. With regard to the SGs, B cells expressed Flt3, while epithelial cells produced FL. (3) Finally, co-cultures revealed that FL potentiated the B cell receptor-induced proliferation of B lymphocytes, and the HSG-mediated survival of B cells was abrogated by anti-FL and/or anti-Flt3 antibodies.

Conclusion

The pSS patients increase their serum levels of FL, relative to the excess of Bm2/Bm2′ in their PB. By supporting the proliferation of B cells, FL favours the development of B cell lymphoma in SS.

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