Cytotoxic T-lymphocyte (CTL)-mediated platelet destruction and aberrant cytokine profiles play important roles in the pathogenesis of primary immune thrombocytopenia (ITP). Interleukin-27 (IL-27) has pleiotropic immunomodulatory effects. However, the effect of IL-27 on CTL activity in ITP has not been reported. In the present study, platelets from ITP patients were cultured with autologous CTLs in the presence of IL-27. We found that IL-27 could inhibit CTL-mediated platelet destruction. In these IL-27-treated CTLs, granzyme B and T-bet expression decreased significantly, whereas granzyme A, perforin, and eomesodermin were not affected. To further investigate the role of granzyme B in CTL-mediated platelet destruction, granzyme B inhibitor was added and platelet apoptosis was significantly inhibited. These results suggest that IL-27 negatively regulates CTL cytotoxicity toward platelets in ITP by decreasing granzyme B expression, which is associated with reduced T-bet expression. IL-27 may have a therapeutic role in treating ITP patients.
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http://dx.doi.org/10.1182/blood-2014-06-580084 | DOI Listing |
Immunotargets Ther
January 2025
Institute of Hematology, Lady Davis Carmel Medical Center, Haifa, Israel.
Multi-refractory immune thrombocytopenia (ITP) is not uncommon and associated with high morbidity and mortality rates. Although the precise mechanism of ITP is not yet fully understood, a therapeutic approach that relies on using a single agent in each treatment line may not be sufficient in this population. We report the case of a 67-year-old female with long-standing multi-refractory ITP treated with a combination of Daratumumab and Romiplostim who achieved a durable response for more than 42 weeks.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, China.
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody-mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high-throughput data, except for the belated emergence of autoreactive antibodies.
View Article and Find Full Text PDFBlood
December 2024
Sanquin, Amsterdam, Netherlands.
Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage.
View Article and Find Full Text PDFCureus
December 2024
General and Family Medicine, Câmara de Lobos Health Center, Serviço de Saúde da Região Autónoma da Madeira, Entidade Pública Empresarial da Região Autónoma da Madeira (SESARAM, EPERAM), Câmara de Lobos, PRT.
Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by a reduced platelet count due to enhanced peripheral destruction and impaired platelet production. While thrombocytopenia is a well-documented complication of various viral infections, cytomegalovirus (CMV), a member of the Herpesviridae family, is primarily associated with infections in immunocompromised patients and is rarely implicated in causing severe thrombocytopenia in immunocompetent patients. This article aims to highlight the importance of considering CMV as a significant etiological factor in ITP, particularly in cases of asymptomatic thrombocytopenia.
View Article and Find Full Text PDFFront Pediatr
December 2024
Pediatric Hematology and Oncology Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Immune thrombocytopenia (ITP) is a disease characterized by platelet destruction, presenting substantial challenges in clinical practice. The classic first line therapeutic management includes corticosteroids and intravenous immunoglobulins. Although it is less frequent in children than in adults, there is a significant percentage of patients, up to 47% according to the Pediatric and Adult Registry on Chronic ITP, who require second-line or further treatment, due to non-response to the first line treatment or persistence of disease, among other reasons.
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