Structural characterisation of immunoglobulin G glycosylation in multiple myeloma

2015 
smoldering MM (SMM). Samples from patients with MGUS and healthy donors were also included in the study. LEN treatment was performed at concentration ranging from 0,1 to 2 M during all the differentiation culture period. Moreover moDC differentiation was performed in the presence of CM of human TERT transfected-hMSCs (hTERT-hMSCs) treated for 5 days with LEN. DC maturation markers (CD83, HLA-DR, CD80, CD86 and CD209) were evaluated by flow cytometry. The levels of soluble factors produced by mo-DCs were measured in the conditioned media (CM) of mo-DC by a Bio-Plex Multiplex System. The expression levels of Ikaros and Aiolos were also evaluated by western blot. LEN treatment induced a reduction of both number and % of mature mo-DC as compared to untreated controls. On the other hand, LEN treatment significantly increased the median intensity expression of CD86 HLA-DR and CD209 but not of CD80 by moDCs derived from BM. Similarly increased CD209 expression has been also seen in mo-DCs derived from PB in both MM and SMM patients. LEN treatment enhanced the production of IL-8 and MCP1 and decreased TNFlevels. Ikaros mediated the effect of LEN on DCs as we observed a significant down-regulation of Ikaros levels in THP1-DCs after LEN treatment with a dose dependent effect. On the other hand, we found that LEN blunted the inhibitory effect of hTERT-hMSCs on mo-DC differentiation in three independent experiments and slightly down-regulated IL-6 and IDO but not TGFB1, IL-8, TNF and HGF gene expression. The effect of LEN on the immunomodulatory properties of hMSC was likely to be not mediated by Ikaros or Aiolos because both transcription factors were not expressed by hMSCs. These evidences underline a possible new effect of IMiDs on the alloreactivity against MM cells.
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