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Published on: December 12, 2014
Elevated Semaphorin 5A correlated with Th1 polarization in patients with chronic immune thrombocytopenia
Mingen Lyu1, Yang Li1, Yating Hao1
1State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China.
Insights
Elevated Semaphorin 5A (Sema5A) in chronic immune thrombocytopenia (ITP) correlates with disease activity and Th1 immune response. Treatment reduced Sema5A and increased its receptor, plexin-B3, suggesting a therapeutic role.
Area of Science:
- Immunology
- Hematology
Background:
- Primary immune thrombocytopenia (ITP) is an immune-mediated disorder characterized by cellular immunity deficiency and altered cytokine profiles.
- Semaphorin 5A (Sema5A) is implicated in cellular immune responses, prompting investigation into its role in chronic ITP.
Purpose of the Study:
- To evaluate the role of Semaphorin 5A (Sema5A) in patients with chronic immune thrombocytopenia (ITP).
Main Methods:
- Plasma levels of Sema5A and T helper (Th) cytokines (IFN-γ, IL-4, IL-17A) were measured using ELISA.
- mRNA levels of Sema5A and its receptors (plexin-B3, plexin-A1) in PBMCs were analyzed by RT-PCR.
- Changes in Sema5A and receptor levels were assessed after effective therapy in ITP patients.
Main Results:
- Plasma Sema5A levels were significantly higher in active chronic ITP patients compared to those in remission and healthy controls.
- Elevated Sema5A correlated positively with IFN-γ and the IFN-γ/IL-4 ratio, and negatively with IL-4 and platelet counts.
- Decreased plexin-B3 mRNA in active ITP patients inversely correlated with plasma Sema5A; treatment normalized Sema5A and IFN-γ levels while up-regulating plexin-B3.
Conclusions:
- Elevated plasma Sema5A in chronic ITP patients is associated with disease activity.
- Sema5A may contribute to Th1 polarization by down-regulating plexin-B3 expression.
- Therapeutic interventions may restore Sema5A/plexin-B3 balance and modulate immune responses in ITP.
Background:
Primary immune thrombocytopenia (ITP) is an immune-mediated disorder in which cellular immunity deficiency and disturbed cytokine profiles have been found. Semaphorin 5A (Sema5A) has been showed to be implicated in cellular immune response. We aimed to evaluate the role of Sema5A in patients with chronic ITP.
Methods:
Plasma levels of Sema5A, T helper (Th) cytokines (interferon [IFN] -γ,interleukin [IL]-4,IL-17A) were determined by enzyme-linked immunosorbent assay (ELISA) in ITP patients and healthy controls. Using real-time quantitative polymerase chain reaction (RT-PCR), mRNA levels of Sema5A and its receptor plexin-B3, plexin-A1 in peripheral blood mononuclear cells(PBMCs)were studied in all subjects. Specific anti-platelet autoantibodies were measured by the Pak Auto method. The dynamic change of plasma Sema5A and mRNA levels of its receptors was measured in 9 patients after effective therapy.
Results:
Plasma Sema5A levels were significantly increased in active patients with chronic ITP compared to patients in remission and healthy controls. Elevated levels of Sema5A were found positively correlated with higher levels of plasma IFN-γ, IFN-γ/IL-4 ratio and negatively correlated with lower levels of plasma IL-4, platelet counts in ITP patients. The mRNA plexin-B3 was decreased in active ITP patients and inversely correlated with plasma Sema5A levels. Additionally, plasma levels of Sema5A and IFN-γ were reduced with up-regulation of plexin-B3 expression after effective treatment.
Conclusions:
Our data demonstrated elevated plasma Sema5A in chronic ITP patients might be involved in Th1 polarization by down-regulating receptor plexin-B3 expression and correlated with disease activity.
