Abnormal immunomodulatory ability on memory T cells in humans with severe aplastic anemia.

In this study we investigate the quantities and functions of memory T cells in SAA patients before and after immunosuppressive therapy (IST) to further clarify the mechanism of SAA apoptosis of bone marrow hematopoietic cells. Results showed that the percentage of CD4+ effector T cells in peripheral blood and bone marrow lymphocytes was decreased in SAA patients. The ratio of CD4+ memory T lymphocytes to CD8+ memory T subsets (CD4+/CD8+TM) in SAA patients was also lower. The percentage of CD8+ effector T cells in peripheral blood and CD8+ central memory T cells in the bone marrow lymphocytes was significantly higher in newly diagnosed patients. Furthermore, the median expressions of perforin and granzyme B on memory T cells were higher in SAA patients compared to those in normal controls. After IST, the quantities and functions of memory T cells return to normal level. Therefore, we concluded that the abnormal immunomodulatory ability on memory T cells may contribute to the imbalance of Th1/Th2 subsets and thus lead to over-function of T lymphocytes and hematopoiesis failure in SAA. PMID: 26097547 [PubMed - in process]
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research

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In this study, we aimed to evaluate the prevalence of PNH clones in 99 patients with primary AIHA, and their correlations with disease features and outcomes. Moreover, in the attempt to disclose the physiopathology of PNH positivity in AIHA, serum levels of several immunomodulatory cytokines were tested. A PNH clone was found in 37 AIHA patients (37,4%), with a median size of 0.2% on granulocytes (range 0.03–85). Two patients showed a large clone (16 and 85%) and were therefore considered as AIHA/PNH association and not included in further analysis. Compared to PNH negative, PNH positive cases displayed a higher hemo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Immunosuppressive therapy has been the standard treatment for patients with severe aplastic anemia (SAA) lacking a matched sibling donor. Prognosis of patients who fail immunosuppression is poor, and hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is one of the most effective available options.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Condition:   Severe Aplastic Anemia (SAA) Intervention:   Drug: REGN7257 Sponsor:   Regeneron Pharmaceuticals Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
In this study, we firstly investigated the expression of OX40, 4-1BB, GITR, ICOS, CTLA-4, LAG-3, and TIM-3 on CD8+ T cells from untreated patients with AA and healthy individuals (HIs) by flow cytometry. Moreover, we further analyzed the phenotype and functional characteristics of CD8+GITR+ T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8+GITR+ T cells in AA, and CD8+GITR+CTLA-4+ T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8+GITR+granzyme B+ and CD8+GITR+perforin+ T ...
Source: Immunological Investigations - Category: Allergy & Immunology Tags: Immunol Invest Source Type: research
Conditions:   Aplastic Anemia;   Drug Effect Interventions:   Drug: Tacrolimus;   Drug: Placebo (for Tacrolimus) Sponsor:   Peking Union Medical College Hospital Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions COVID-19 may be associated with an acute severe encephalopathy and, in this case, was considered most likely to represent an immune-mediated phenomenon. As the pandemic continues, we anticipate that the spectrum of neurologic presentation will broaden. It will be important to delineate the full clinical range of emergent COVID-19-related neurologic disease.
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: MRI, Encephalitis, Viral infections, COVID-19 Article Source Type: research
In conclusion, EPAG was well-tolerated and effective in restoring hematopoiesis in patients with low to intermediate-1 risk MDS. This study was registered at clinicaltrials.gov as #NCT00932156. PMID: 32439728 [PubMed - as supplied by publisher]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Abstract Leukocytes that lack HLA allelic expression are frequently detected in patients with acquired aplastic anemia (AA) who respond to immunosuppressive therapy (IST), although the exact mechanisms underlying the HLA loss and HLA allele repertoire likely to acquire loss-of-function mutations are unknown. We identified a common nonsense mutation at position 19 (c.19C>T, p.R7X) in exon 1 (Exon1mut ) of different HLA-A and -B alleles in HLA-lacking granulocytes from AA patients. A droplet digital PCR (ddPCR) assay capable of detecting as few as 0.07% Exon1mut HLA alleles in total DNA revealed the mutation was ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
In case you were ever stupid enough to follow Trump’s lead you would have already injected ultraviolets in your eyeballs by now to save you from Covid and maybe bathed in Domestos or sulfuric acid or both! Anyway, his latest bullshine claim is that he’s been taking the antimalarial drug hydroxychloroquine to keep Covid at bay. Well, for starters there is no evidence that this drug acts as a prophylactic against infection with SARS CoV-2 or indeed any pathogen other than the causative agent of otherwise drug-resistant malaria. It’s primary use is in treating lupus. There was some testing done weeks ago to...
Source: David Bradley Sciencebase - Songs, Snaps, Science - Category: Science Authors: Tags: Health and Medicine Source Type: blogs
Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure (BMF; cytopenia or aplastic anemia), exocrine pancreatic insufficiency, and skeletal abnormalities, with a predisposition to myelodysplasia (MDS) and acute myeloid leukemia (AML)1. Although most individuals with SDS have some hematologic manifestations of their disease, the majority of them do not require transplantation. Hematopoietic stem cell transplantation (HSCT), however, remains the only curative therapy for 19-36 % of patients with SDS who develop BMF or transformation to myeloid malignancy.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
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