Abstract: P424
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: The aim of this study is to evaluate the effects of fingolimod on the natural killer (NK) cells, in relapsing remitting multiple sclerosis (RRMS) patients during fingolimod treatment.
Background: Fingolimod (FTY720), an oral sphingosine 1-phosphate modulator inhibits the egress of
T cells from lymph nodes acting specifically on naïve and memory T cells and sparing effector T cells. Fingolimod may also modulate peripheral effector and regulatory T cells in MS patients.There are few studies about the effect of fingolimod theraphy on NK cells.
Methods: Age and sex matched healthy volunteers (HV, n=16) and RRMS patients receiving other immunomodulatory drugs (MS-IMT, n=23) were taken as the control group; RRMS patients under fingolimod treatment were divided into three groups according to the duration of the treatment (1 month (n=15), 3-6 months (n=16), 12-24 months (n=15)). Leukocytes were isolated and expression of T and NK cell markers (CD3, CD16, CD56, CCR7, NKG2D, NKp46) were analyzed with multi-color flow cytometry. Additionally, leukocytes were co-cultured with K562 cell line to evaluate the activation of NK cells. IFN-gamma production and degranulation of NK cells were also assessed.
Results: After fingolimod treatment, beginning from the first month, lymphocyte number; percentage and number of T lymphocytes and CCR7 expression were decreased. The percentage of NK cells were significantly higher in the fingolimod treatment groups than MS-IMT controls (p=0,001; p=0,000; p=0,024). CCR7 expression was also decreased on these NK cells in the first six months of fingolimod compared with HV (p=0,004). The percentage of CD56dim NK sub-population and NKp46, NKG2D cytotoxicity markers did not change significantly during the treatment. On the other hand, CD107a expression indicating degranulation activity of NK cells was higher in the 12 - 24 months of the fingolimod treatment compared with earlier months and MS-IMT (p=0,038; p=0,009, respectively). Patient-derived NK cells retained capacity to highly degranulate and produce IFN-g upon stimulation with K562 target cells.
Conclusion: Even though the number of NK cells was also affected by treatment with fingolimod, these cells did not lose their functional capacity. Our results may indicate the importance of NK cells for immune competency in the absence of T lymphocytes in RRMS patients under fingolimod therapy.
Disclosure:
Nazire Pınar Acar: nothing to disclose
Didem Özkazanç: nothing to disclose
Güneş Esendağlı: nothing to disclose
Güliz Sayat: nothing to disclose
Rana Karabudak: nothing to disclose
Aslı Tuncer: nothing to disclose
Abstract: P424
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: The aim of this study is to evaluate the effects of fingolimod on the natural killer (NK) cells, in relapsing remitting multiple sclerosis (RRMS) patients during fingolimod treatment.
Background: Fingolimod (FTY720), an oral sphingosine 1-phosphate modulator inhibits the egress of
T cells from lymph nodes acting specifically on naïve and memory T cells and sparing effector T cells. Fingolimod may also modulate peripheral effector and regulatory T cells in MS patients.There are few studies about the effect of fingolimod theraphy on NK cells.
Methods: Age and sex matched healthy volunteers (HV, n=16) and RRMS patients receiving other immunomodulatory drugs (MS-IMT, n=23) were taken as the control group; RRMS patients under fingolimod treatment were divided into three groups according to the duration of the treatment (1 month (n=15), 3-6 months (n=16), 12-24 months (n=15)). Leukocytes were isolated and expression of T and NK cell markers (CD3, CD16, CD56, CCR7, NKG2D, NKp46) were analyzed with multi-color flow cytometry. Additionally, leukocytes were co-cultured with K562 cell line to evaluate the activation of NK cells. IFN-gamma production and degranulation of NK cells were also assessed.
Results: After fingolimod treatment, beginning from the first month, lymphocyte number; percentage and number of T lymphocytes and CCR7 expression were decreased. The percentage of NK cells were significantly higher in the fingolimod treatment groups than MS-IMT controls (p=0,001; p=0,000; p=0,024). CCR7 expression was also decreased on these NK cells in the first six months of fingolimod compared with HV (p=0,004). The percentage of CD56dim NK sub-population and NKp46, NKG2D cytotoxicity markers did not change significantly during the treatment. On the other hand, CD107a expression indicating degranulation activity of NK cells was higher in the 12 - 24 months of the fingolimod treatment compared with earlier months and MS-IMT (p=0,038; p=0,009, respectively). Patient-derived NK cells retained capacity to highly degranulate and produce IFN-g upon stimulation with K562 target cells.
Conclusion: Even though the number of NK cells was also affected by treatment with fingolimod, these cells did not lose their functional capacity. Our results may indicate the importance of NK cells for immune competency in the absence of T lymphocytes in RRMS patients under fingolimod therapy.
Disclosure:
Nazire Pınar Acar: nothing to disclose
Didem Özkazanç: nothing to disclose
Güneş Esendağlı: nothing to disclose
Güliz Sayat: nothing to disclose
Rana Karabudak: nothing to disclose
Aslı Tuncer: nothing to disclose