Contributions
Abstract: PB2545
Type: Publication Only
Background
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the presence of autoantibodies against platelet membrane glycoproteins, such as GPIIb/IIIa. An in vitro study showed that plasma containing anti-GPIIb/IIIa antibodies from adults with severe ITP inhibited the maturation of hematopoietic stem cells into megakaryocytes. In addition, some patients with ITP had anti-thrombopoietin receptor (TPOR) antibodies that suppressed megakaryocyte differentiation. Eltrombopag is a TPOR agonist that increases platelet counts by stimulating the differentiation and proliferation of megakaryocytes in ITP.
Aims
To determine the prevalence and pathogenic role of anti-TPOR antibodies in Japanese patients with ITP.
Methods
Anti-TPOR antibodies from 132 patients with ITP and 70 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). TPO levels in platelet-poor plasma were measured using an ELISA kit. To investigate whether anti-TPOR antibodies inhibited functional interactions between TPO and TPO receptors, we examined extracellular signal-regulated kinases (ERKs), downstream signals induced by recombinant human TPO (rhTPO). The binding of rhTPO to TPO receptors induced the phosphorylation of ERK in TPOR-expressing UT-7/TPO cells. Furthermore, for functional analyses, eltrombopag was used instead of rhTPO.
Results
Anti-TPOR antibodies were detected in fifteen ITP patients (11.4%) and none of the healthy controls. There was no difference in plasma TPO levels between ITP patients with anti-TPOR antibodies and patients without anti-TPOR antibodies (77.5 ± 78.7 pg/ml versus 52.7 ± 57.4 pg/ml). Six of 10 anti-TPOR antibody-positive samples inhibited the phosphorylation of ERK in UT-7/TPO cells, which might be related to the blocking of rhTPO by anti-TPOR antibodies. In contrast, healthy control and anti-TPOR antibody-negative samples had no inhibitory effect. Eltrombopag improved the phosphorylation of ERK in UT-7/TPO cells in the presence of functional anti-TPOR antibodies.
Conclusion
Our findings suggest that functional anti-TPOR antibodies impair megakaryocyte differentiation and proliferation in patients with ITP. Eltrombopag might be a therapeutic option for ITP patients with anti-TPOR antibodies.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Autoantibody, ITP
Abstract: PB2545
Type: Publication Only
Background
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the presence of autoantibodies against platelet membrane glycoproteins, such as GPIIb/IIIa. An in vitro study showed that plasma containing anti-GPIIb/IIIa antibodies from adults with severe ITP inhibited the maturation of hematopoietic stem cells into megakaryocytes. In addition, some patients with ITP had anti-thrombopoietin receptor (TPOR) antibodies that suppressed megakaryocyte differentiation. Eltrombopag is a TPOR agonist that increases platelet counts by stimulating the differentiation and proliferation of megakaryocytes in ITP.
Aims
To determine the prevalence and pathogenic role of anti-TPOR antibodies in Japanese patients with ITP.
Methods
Anti-TPOR antibodies from 132 patients with ITP and 70 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). TPO levels in platelet-poor plasma were measured using an ELISA kit. To investigate whether anti-TPOR antibodies inhibited functional interactions between TPO and TPO receptors, we examined extracellular signal-regulated kinases (ERKs), downstream signals induced by recombinant human TPO (rhTPO). The binding of rhTPO to TPO receptors induced the phosphorylation of ERK in TPOR-expressing UT-7/TPO cells. Furthermore, for functional analyses, eltrombopag was used instead of rhTPO.
Results
Anti-TPOR antibodies were detected in fifteen ITP patients (11.4%) and none of the healthy controls. There was no difference in plasma TPO levels between ITP patients with anti-TPOR antibodies and patients without anti-TPOR antibodies (77.5 ± 78.7 pg/ml versus 52.7 ± 57.4 pg/ml). Six of 10 anti-TPOR antibody-positive samples inhibited the phosphorylation of ERK in UT-7/TPO cells, which might be related to the blocking of rhTPO by anti-TPOR antibodies. In contrast, healthy control and anti-TPOR antibody-negative samples had no inhibitory effect. Eltrombopag improved the phosphorylation of ERK in UT-7/TPO cells in the presence of functional anti-TPOR antibodies.
Conclusion
Our findings suggest that functional anti-TPOR antibodies impair megakaryocyte differentiation and proliferation in patients with ITP. Eltrombopag might be a therapeutic option for ITP patients with anti-TPOR antibodies.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Autoantibody, ITP