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关键词： Neonatal alloimmune thrombocytopenia   Human platelet antigen   Human leukocyte antigen   Multiple alloantibodies  

摘要： Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is primarily caused by the transplacental passage of maternal antibodies commonly directed against fetal human platelet antigens (HPA) and rarely against human leukocyte antigens (HLA). Study design and methods Here, we report a case of prolonged neonatal alloimmune thrombocytopenia (NAIT) associated with three anti-HLA antibodies. A male infant was delivered at 37 weeks' gestation because of non-reassuring fetal status. His platelet count decreased to 14 x 10(9)/L on postnatal day 8. A random-donor platelet transfusion and intravenous immunoglobulin were administered without clinical complications. Immunoserological investigations were performed to identify HLA, HPA, and antibodies in the patient and his parents. Results Anti-HLA-A11, -B3901, and -Cw7 antibodies, but not anti-HPA antibodies, were identified in the mother's blood that reacted with the lymphocytes of the infant and his father. Conclusion Three distinct anti-HLA (HLA-A11, B3901, and Cw7) may have caused the prolonged neonatal thrombocytopenia observed in the present case. This case report demonstrates the role of anti-HLA antibodies in the pathogenesis of FNAIT.

关键词： MK2   inflammatory bowel disease   Th1   Th17   inflammation   fibrosis  

摘要： Background CD4+ T cells contribute to chronic inflammation and fibrosis in inflammatory bowel disease (IBD), but the cellular mechanisms remain elusive. We have found that the mitogen-activated protein kinase 2 (MK2) pathway plays a major role in inflammation and overall pathology in IBD. Thus, here, we examined the role of MK2 in regulating CD4+ T cell responses in IBD *** Interleukin-10 (IL-10) knockout (KO) mice treated with MK2 inhibitors (MK2i) and CD4-specific MK2 knockdown mice treated with chronic dextran sodium sulfate (DSS) treatments were used to examine inflammation and fibrosis by multiplex array, gene expression, flow cytometry, and histology. Human tissues were treated with MK2i to examine Th1 and Th17 *** IL-10 KO mice treated with MK2i therapeutically showed significantly reduced interferon gamma (IFN gamma) and interleukin-17A (IL-17A) and a significantly reduced number of IFN gamma+ and IL-17A+ producing CD4+ T cells by flow cytometry. To investigate the direct role of MK2 in CD4+ T cells during IBD, we utilized CD4-specific MK2 knockdown mice in chronic DSS colitis. A decrease in colonic inflammation, IFN gamma and IL-17, pro-fibrotic genes, and extracellular matrix deposition was observed in mice with MK2 knockdown in CD4+ T cells compared to control mice. Additionally, IL-17A and IFN gamma directly regulated the expression of fibrosis genes in colon *** IL-10 KO mice treated with MK2i therapeutically showed significantly reduced interferon gamma (IFN gamma) and interleukin-17A (IL-17A) and a significantly reduced number of IFN gamma+ and IL-17A+ producing CD4+ T cells by flow cytometry. To investigate the direct role of MK2 in CD4+ T cells during IBD, we utilized CD4-specific MK2 knockdown mice in chronic DSS colitis. A decrease in colonic inflammation, IFN gamma and IL-17, pro-fibrotic genes, and extracellular matrix deposition was observed in mice with MK2 knockdown in CD4+ T cells compared to control mice.

关键词： biological DMARD   Clinical Trial   Disease-modifying Drugs (DMARDS)   Randomised controlled trial  

关键词： Biomarkers   Biomarkers   Cytokines and Chemokines  

摘要： Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, vasculopathy, and fibrosis, with B cell activation playing a critical role in its pathogenesis [1]. Interleukin-40 (IL-40), primarily produced by activated B cells, has been implicated as a potential biomarker in autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, due to its role in inflammation and humoral immune responses [2]. The elevated expression of B cell-related molecules like IL-40 and BAFF in SSc suggests their involvement in fibrosis and disease progression. Objectives: This study aims to evaluate the role of IL-40 in the pathogenesis of systemic sclerosis by assessing its relationship with clinical findings and disease activity and investigating the correlation between IL-40 levels and immunosuppressive therapies. Methods: This study recruited 47 systemic sclerosis (SSc) patients meeting the 2013 ACR/EULAR classification criteria, categorized into three subgroups based on disease activity and immunosuppressive therapy status, alongside 30 age- and sex-matched healthy controls. Clinical assessments included symptoms, serological markers, and immunosuppressive therapy status, with IL-40 serum levels measured via ELISA from stored samples. Results: This study evaluated 47 systemic sclerosis (SSc) patients, primarily female (93.6%), with a mean age of 44.7 years and median disease duration of 9 years. Patients were classified into diffuse SSc (44.7%), limited SSc (46.8%), and overlap syndrome (8.5%). Common manifestations included Raynaud phenomenon (93.6%), sclerodactyly (89.4%), interstitial lung disease (46.8%), and esophageal dysphagia (46.8%). Serologically, anti-nuclear antibody positivity was observed in 89.4%, anti-topoisomerase I in 61.7%, and anti-centromere antibody in 19.1%. Patients were categorized into three subgroups based on disease activity and immunosuppressive therapy status. The patients currently receiving immun

关键词： IFN-γ   IL-18   adjuvant   cancer immunotherapy   cancer rejection   innate immunity   protective immunity  

摘要： Our recent study demonstrated that immunizations with nonreplicable MC38 colorectal cancer cells plus a novel recombinant protein adjuvant, the amino-terminus region of dense granule protein 6 (rGRA6Nt) of (a protozoan parasite), effectively activate the cancer cell-specific CD8 T cytotoxic cells and inhibit the growth of implanted tumors of the identical cancer cells after its challenge implantation. In the present study, we first examined whether rGRA6Nt activates mRNA expression for IFN-γ, IL-12, IL-15, and IL-18, which are known to assist an activation of the CD8 T cells, in innate immune cells. Following an intraperitoneal injection of rGRA6Nt (40 μg) into SCID mice deficient in both T and B cells, markedly increased levels of mRNA for only IFN-γ and IL-18 were detected in their peritoneal exudate innate immune cells. When C57BL/6 mice were immunized with nonreplicable MC38 colorectal cancer cells plus rGRA6Nt adjuvant twice and challenged with replication-capable cancer cells of the identical colorectal cancer, more than one fifth (22.2%, 6/27) of the immunized mice rejected the growth of the implanted tumors, whereas none (0/27, <0.05) of unimmunized control mice rejected the implanted tumors. These results indicate that rGRA6Nt protein adjuvant has a unique capability to selectively activate expression of IFN-γ and IL-18 in innate immune cells, and that immunizations with nonreplicable cancer cells in combination with this protein adjuvant can induce a protection to reject the growth of the identical tumor cells after its challenge implantation in a significant portion of the immunized mice.

关键词： Cytokines and Chemokines   Animal Models   Anti-Inflammatory Agents   Non-Steroidal  

关键词： Epigenetics   Innate immunity   Adaptive immunity   Autoantibodies  

关键词： genomic full-length   HLA-DRB1*04:90   PacBio sequencing  

摘要： The complete genomic sequence of HLA-DRB1*04:90 was determined using a PacBio sequencing approach conducted in China.