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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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Related in: MedlinePlus

Correlation of auto-immune serology and sIL2Rα levels in patients with MPN diseases.Auto-immune serology panels were performed as outlined in the materials and methods. 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Patients with at least one positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05)
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pone.0116723.g006: Correlation of auto-immune serology and sIL2Rα levels in patients with MPN diseases.Auto-immune serology panels were performed as outlined in the materials and methods. 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Patients with at least one positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05)

Mentions: 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Nine MF patients had positive serology including two with ANA(+), four with positive anti-cardiolipin antibody, two with positive lupus-anticoagulant.and one with positive to thyroglobulin. Four ET patients had positive serology including two with positive ANA, one with positive rheumatic factor, and one with positive cardiolipin antibody. Four PV patients with positive serology including one with positive ANA, one positive anti-thyroglobulin, and two with positive anti-cardiolipin antibody. As shown in Fig. 6, 17 patients who were positive for any one of the auto-immune serology were compared with 14 patients with negative serology. Patients with positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05).


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)

Correlation of auto-immune serology and sIL2Rα levels in patients with MPN diseases.Auto-immune serology panels were performed as outlined in the materials and methods. 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Patients with at least one positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05)
© Copyright Policy
Related In: Results  -  Collection

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

pone.0116723.g006: Correlation of auto-immune serology and sIL2Rα levels in patients with MPN diseases.Auto-immune serology panels were performed as outlined in the materials and methods. 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Patients with at least one positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05)
Mentions: 31 patients including PMF (9) ET-MF(1) PV-MF(4), ET(8), PV(9) were studied. Nine MF patients had positive serology including two with ANA(+), four with positive anti-cardiolipin antibody, two with positive lupus-anticoagulant.and one with positive to thyroglobulin. Four ET patients had positive serology including two with positive ANA, one with positive rheumatic factor, and one with positive cardiolipin antibody. Four PV patients with positive serology including one with positive ANA, one positive anti-thyroglobulin, and two with positive anti-cardiolipin antibody. As shown in Fig. 6, 17 patients who were positive for any one of the auto-immune serology were compared with 14 patients with negative serology. Patients with positive serology have significantly elevated sIL2Rα levels compared to negative patients (p<0.05).

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