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Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα.

Wang JC, Sindhu H, Chen C, Kundra A, Kafeel MI, Wong C, Lichter S - PLoS ONE (2015)

Bottom Line: However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls.Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells.Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, New York, United States of America.

ABSTRACT
Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.

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Plasma sIL-2Rα levels in Patients with MF and others.Levels of sIL2Rα in peripheral plasma were quantified using BD OptEIA ELISA set for human sIL-2Rα. MF patients had a significantly elevated sIL-2Rα compared with other MPN patients and controls. Other MPN patients were not significantly different from controls. MF = myelofibrosis, MPN = myeloproliferative neoplasm, CTR = control. ***P<0.0001, **P< 0.0001, NS = no significance.
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pone.0116723.g003: Plasma sIL-2Rα levels in Patients with MF and others.Levels of sIL2Rα in peripheral plasma were quantified using BD OptEIA ELISA set for human sIL-2Rα. MF patients had a significantly elevated sIL-2Rα compared with other MPN patients and controls. Other MPN patients were not significantly different from controls. MF = myelofibrosis, MPN = myeloproliferative neoplasm, CTR = control. ***P<0.0001, **P< 0.0001, NS = no significance.

Mentions: We previously found plasma sIL2Rα levels were significantly elevated in patients with MF compared with MPN patients and controls [36]. We repeated the study and found that MF patients had significantly elevated plasma sIL2Rα levels compared with other MPN patients and controls (Fig. 3).


Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα.

Wang JC, Sindhu H, Chen C, Kundra A, Kafeel MI, Wong C, Lichter S - PLoS ONE (2015)

Plasma sIL-2Rα levels in Patients with MF and others.Levels of sIL2Rα in peripheral plasma were quantified using BD OptEIA ELISA set for human sIL-2Rα. MF patients had a significantly elevated sIL-2Rα compared with other MPN patients and controls. Other MPN patients were not significantly different from controls. MF = myelofibrosis, MPN = myeloproliferative neoplasm, CTR = control. ***P<0.0001, **P< 0.0001, NS = no significance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368690&req=5

pone.0116723.g003: Plasma sIL-2Rα levels in Patients with MF and others.Levels of sIL2Rα in peripheral plasma were quantified using BD OptEIA ELISA set for human sIL-2Rα. MF patients had a significantly elevated sIL-2Rα compared with other MPN patients and controls. Other MPN patients were not significantly different from controls. MF = myelofibrosis, MPN = myeloproliferative neoplasm, CTR = control. ***P<0.0001, **P< 0.0001, NS = no significance.
Mentions: We previously found plasma sIL2Rα levels were significantly elevated in patients with MF compared with MPN patients and controls [36]. We repeated the study and found that MF patients had significantly elevated plasma sIL2Rα levels compared with other MPN patients and controls (Fig. 3).

Bottom Line: However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls.Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells.Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, New York, United States of America.

ABSTRACT
Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.

Show MeSH
Related in: MedlinePlus