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Journal of the American Veterinary... Aug 2019To characterize the clinical features of dogs with precursor-targeted immune-mediated anemia (PIMA).
OBJECTIVE
To characterize the clinical features of dogs with precursor-targeted immune-mediated anemia (PIMA).
ANIMALS
66 dogs with PIMA.
PROCEDURES
Electronic record databases of a teaching hospital were searched to identify dogs with a diagnosis of nonregenerative anemia between 2004 and 2013. Inclusion criteria included persistent nonregenerative anemia (Hct ≤ 30% and reticulocyte count < 76,000 reticulocytes/μL), cytologic findings supportive of ineffective bone marrow erythropoiesis, and absence of underlying disease. Information regarding clinical signs, clinicopathologic findings, treatment, and outcome was extracted from records of eligible dogs. A regenerative response was defined as a reticulocyte count > 76,000 reticulocytes/μL or sustained increase in Hct of > 5%. Remission was defined as a stable Hct ≥ 35%.
RESULTS
The median Hct was 13%, and reticulocyte count was 17,900 reticulocytes/μL. Rubriphagocytosis was identified in bone marrow aspirate samples from 61 of 66 dogs. Collagen myelofibrosis was detected in bone marrow biopsy specimens obtained from 31 of 63 dogs. Immune-mediated targeting of mature erythrocytes was uncommon. All dogs received immunosuppressive therapy. Fifty-five dogs developed a regenerative response at a median of 29 days, and 40 of those dogs went into remission at a median of 59 days after PIMA diagnosis. Thromboembolic events were confirmed for 9 dogs and were associated with a decreased survival time. Median survival time was 913 days for all dogs.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that most dogs with PIMA responded to prolonged immunosuppressive therapy. Studies to determine optimal immunosuppressive and thromboprophylactic protocols for dogs with PIMA are warranted.
Topics: Anemia; Animals; Bone Marrow; Dog Diseases; Dogs; Immunosuppressive Agents; Reticulocytes
PubMed: 31298643
DOI: 10.2460/javma.255.3.366 -
Current Opinion in Hematology May 2011Reticulocyte remodeling has emerged as an important model for the understanding of vesicular trafficking and selective autophagy in mammalian cells. This review covers... (Review)
Review
PURPOSE OF REVIEW
Reticulocyte remodeling has emerged as an important model for the understanding of vesicular trafficking and selective autophagy in mammalian cells. This review covers recent advances in our understanding of these processes in reticulocytes and the role of these processes in erythroid development.
RECENT FINDINGS
Enucleation is caused by the coalescence of vesicles at the nuclear-cytoplasmic junction and microfilament contraction. Mitochondrial elimination is achieved through selective autophagy, in which mitochondria are targeted to autophagosomes, and undergo subsequent degradation and exocytosis. The mechanism involves an integral mitochondrial outer membrane protein and general autophagy pathways. Plasma membrane remodeling, and the elimination of certain intracellular organelles occur through the exosomal pathway.
SUMMARY
Vesicular trafficking and selective autophagy have emerged as central processes in cellular remodeling. In reticulocytes, this includes enucleation and the elimination of all membrane-bound organelles and ribosomes. Ubiquitin-like conjugation pathways, which are required for autophagy in yeast, are not essential for mitochondrial clearance in reticulocytes. Thus, in higher eukaryotes, there appears to be redundancy between these pathways and other processes, such as vesicular nucleation. Future studies will address the relationship between autophagy and vesicular trafficking, and the significance of both for cellular remodeling.
Topics: Animals; Autophagy; Erythropoiesis; Humans; Reticulocytes
PubMed: 21423015
DOI: 10.1097/MOH.0b013e328345213e -
Nature Communications Mar 2021The structural integrity of the host red blood cell (RBC) is crucial for propagation of Plasmodium spp. during the disease-causing blood stage of malaria infection. To...
The structural integrity of the host red blood cell (RBC) is crucial for propagation of Plasmodium spp. during the disease-causing blood stage of malaria infection. To assess the stability of Plasmodium vivax-infected reticulocytes, we developed a flow cytometry-based assay to measure osmotic stability within characteristically heterogeneous reticulocyte and P. vivax-infected samples. We find that erythroid osmotic stability decreases during erythropoiesis and reticulocyte maturation. Of enucleated RBCs, young reticulocytes which are preferentially infected by P. vivax, are the most osmotically stable. P. vivax infection however decreases reticulocyte stability to levels close to those of RBC disorders that cause hemolytic anemia, and to a significantly greater degree than P. falciparum destabilizes normocytes. Finally, we find that P. vivax new permeability pathways contribute to the decreased osmotic stability of infected-reticulocytes. These results reveal a vulnerability of P. vivax-infected reticulocytes that could be manipulated to allow in vitro culture and develop novel therapeutics.
Topics: Anemia, Hemolytic; Bone Marrow; Cell Differentiation; Erythrocytes; Hemolysis; Humans; Malaria; Malaria, Vivax; Plasmodium vivax; Reticulocytes
PubMed: 33712609
DOI: 10.1038/s41467-021-21886-x -
Journal of Clinical Laboratory Analysis 2001
Review
Topics: Anemia; Antibodies, Monoclonal; Bone Marrow Transplantation; Cellular Senescence; Erythropoiesis; Flow Cytometry; Humans; Kidney Failure, Chronic; Microscopy; Microscopy, Fluorescence; Reticulocyte Count; Reticulocytes
PubMed: 11574956
DOI: 10.1002/jcla.1039 -
World Journal of Gastroenterology Oct 2009Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia,... (Review)
Review
Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification (microcytic, macrocytic and normocytic) and pathogenic classification (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time.
Topics: Anemia; Anemia, Macrocytic; Erythrocyte Indices; Gastroenterology; Hemoglobins; Humans; Reticulocyte Count; Reticulocytes
PubMed: 19787825
DOI: 10.3748/wjg.15.4627 -
Medicine Apr 2023Hepcidin is an essential regulator of iron homeostasis in chronic kidney disease (CKD) anemia, reticulocyte hemoglobin equivalent (RET-He) can be used to evaluate the...
Hepcidin is an essential regulator of iron homeostasis in chronic kidney disease (CKD) anemia, reticulocyte hemoglobin equivalent (RET-He) can be used to evaluate the availability of iron for erythropoiesis. Previous research has found that hepcidin indirectly regulates RET-He. This study aimed to investigate the association of hepcidin, RET-He and anemia-related indicators on anemia in chronic kidney disease. A total of 230 individuals were recruited, including 40 CKD3-4 patients, 70 CKD5 patients without renal replacement therapy, 50 peritoneal dialysis patients, and 70 hemodialysis patients. The serum levels of hemoglobin (Hb), reticulocyte, RET-He, serum iron, serum creatinine, serum ferritin, total iron binding capacity, hepcidin-25, high sensitivity C-reactive protein, transferrin, erythropoietin, intrinsic factor antibody, soluble transferrin receptor and interleukins-6 (IL-6) were measured. Hepcidin-25 was positively associated with IL-6, and negatively with total iron binding capacity, intrinsic factor antibody, and transferrin. Reticulocyte Hb equivalent was associated positively with Hb, serum ferritin, serum iron, transferrin saturation, and negatively with serum creatinine, reticulocyte, IL-6, STfR. Hepcidin-25 was not associated with RET-He, while IL-6 was independently associated with hepcidin-25 and RET-He, suggesting that hepcidin has no effffect on the iron dynamics of reticulocytes in CKD, may be related to IL-6, indicate a likelihood of a threshold for stimulation of hepcidin-25 expression by IL-6 in order to indirectly regulates RET-He.
Topics: Humans; Reticulocytes; Hepcidins; Anemia, Iron-Deficiency; Intrinsic Factor; Interleukin-6; Creatinine; Anemia; Iron; Renal Insufficiency, Chronic; Hemoglobins; Transferrin; Ferritins
PubMed: 37115087
DOI: 10.1097/MD.0000000000033558 -
Blood Advances Sep 2019The capacity to undergo substantial deformation is a defining characteristic of the red blood cell (RBC), facilitating transit through the splenic interendothelial slits...
The capacity to undergo substantial deformation is a defining characteristic of the red blood cell (RBC), facilitating transit through the splenic interendothelial slits and microvasculature. Establishment of this remarkable property occurs during a process of reticulocyte maturation that begins with egress through micron-wide pores in the bone marrow and is completed within the circulation. The requirement to undertake repeated cycles of deformation necessitates that both reticulocytes and erythrocytes regulate membrane-cytoskeletal protein interactions in order to maintain cellular stability. In the absence of transcriptional activity, modulation of these interactions in RBCs is likely to be achieved primarily through specific protein posttranslational modifications, which at present remain undefined. In this study, we use high-throughput methods to define the processes that underlie the response to deformation and shear stress in both reticulocytes and erythrocytes. Through combination of a bead-based microsphiltration assay with phosphoproteomics we describe posttranslational modification of RBC proteins associated with deformation. Using microsphiltration and microfluidic biochip-based assays, we explore the effect of inhibiting kinases identified using this dataset. We demonstrate roles for GSK3 and Lyn in capillary transit and maintenance of membrane stability following deformation and show that combined inhibition of these kinases significantly decreases reticulocyte capacity to undergo repeated deformation. Finally, we derive a comprehensive and integrative phosphoproteomic dataset that provides a valuable resource for further mechanistic dissection of the molecular pathways that underlie the RBC's response to mechanical stimuli and for the study of reticulocyte maturation.
Topics: Cell Shape; Cells, Cultured; Erythrocyte Deformability; Erythrocyte Membrane; Erythrocytes; Glycogen Synthase Kinase 3; Humans; Membrane Proteins; Phosphorylation; Protein Processing, Post-Translational; Proteomics; Reticulocytes; src-Family Kinases
PubMed: 31506283
DOI: 10.1182/bloodadvances.2019000545 -
Mutation Research Dec 2007A flow cytometric, anti-CD71-based method was used to measure peripheral blood reticulocyte and micronucleated reticulocyte frequencies in response to (137)Cs total body...
A flow cytometric, anti-CD71-based method was used to measure peripheral blood reticulocyte and micronucleated reticulocyte frequencies in response to (137)Cs total body irradiation (TBI). In three independent experiments, groups of five female C57BL/6N mice were irradiated at graded doses up to 3 Gy, and peripheral blood specimens were collected at 43 h post-irradiation. Whereas the frequency of reticulocytes declined over the range of doses studied, micronucleated reticulocyte incidence was observed to increase in a dose-dependent manner up to 1 Gy. At doses greater than approximately 1 Gy, micronucleated reticulocyte frequencies declined with increasing exposure. These responses were highly reproducible, with significant effects on reticulocyte and micronucleated reticulocyte frequencies observed for the lowest dose studied (0.125 Gy). A time-course experiment was performed to test whether radiation-induced cell cycle delay may explain saturation of the micronucleated reticulocyte endpoint at doses >1 Gy. For this experiment, groups of four female C57BL/6N mice were exposed to 1, 1.5, or 2 Gy TBI, and blood collection occurred at 12h intervals from 43 to 115 h post-exposure. Reduced reticulocyte frequencies were observed for each dose studied, and the recovery of reticulocytes was increasingly delayed with higher radiation doses. Maximal micronucleated reticulocyte frequencies were observed at 43 or 55 h, with progressively lower values at later time points. At no time did micronucleated reticulocyte frequencies induced by 1.5 or 2 Gy significantly exceed that observed for 1 Gy at 43 h. These time-course data suggest that radiation-induced cell cycle delay cannot account for the micronucleated reticulocyte downturn phenomenon observed at doses greater than 1 Gy. An alternate hypothesis is discussed whereby apoptotic elimination of severely damaged bone marrow erythroid precursors plays a dominant role in saturating the radiation-induced micronucleated reticulocyte response observed for C57BL/6N mice.
Topics: Animals; Cesium Radioisotopes; Dose-Response Relationship, Radiation; Female; Flow Cytometry; Mice; Micronuclei, Chromosome-Defective; Micronucleus Tests; Models, Biological; Reticulocytes; Time Factors; Whole-Body Irradiation
PubMed: 17686648
DOI: 10.1016/j.mrgentox.2007.06.010 -
Journal of Clinical Laboratory Analysis 2011Red blood cells (RBCs) extended parameters or erythrocyte subsets are now reported by the new Sysmex XE 5000 analyzer. This study was aimed at establishing a...
INTRODUCTION
Red blood cells (RBCs) extended parameters or erythrocyte subsets are now reported by the new Sysmex XE 5000 analyzer. This study was aimed at establishing a characteristic analytical feature, including the new erythrocyte and reticulocyte parameters, in case of thalassemia trait and iron deficiency (IDA).
METHODS
Ninety healthy individuals, 136 β-thalassemia carriers, 121 mild IDA, and 126 severe IDA patients were analyzed.
RESULTS
The values obtained for the RBC extended parameters were significantly different (P<0.0001) in the groups; the only exception was %Hypo-He in the case of mild IDA and thalassemia (P=0.6226). %Hypo-He was considerably greater in severe IDA (23.4%) than in mild cases (12.4%), P<0.0001. %MicroR was more increased in thalassemia (38.6 %) than in the mild IDA (16.5%, P<0.001) and in severe IDA (21.6%, P<0.001). Immature reticulocyte fraction (IRF) mean values in the groups were statistically different; the thalassemia group had an intermediate value (8.7%) between healthy (4.4%) and IDA (16.7 and 12.9%).
CONCLUSIONS
Erythrocytosis and severe microcytosis, together with a high percentage of microcytes and a moderate increase in IRF, is the profile of β-thalassemia carriers, whereas anisocytosis and the hypochromic subset correlates with the severity of the anemia in iron-deficient patients.
Topics: Adult; Anemia, Iron-Deficiency; Case-Control Studies; Female; Humans; Male; Reticulocytes; Thalassemia
PubMed: 21567473
DOI: 10.1002/jcla.20462 -
Current Opinion in Microbiology Dec 2018Plasmodium vivax is uniquely restricted to invading reticulocytes, the youngest of red blood cells. Parasite invasion relies on the sequential deployment of multiple... (Review)
Review
Plasmodium vivax is uniquely restricted to invading reticulocytes, the youngest of red blood cells. Parasite invasion relies on the sequential deployment of multiple parasite invasion ligands. Correct targeting of the host reticulocyte is mediated by two families of invasion ligands: the reticulocyte binding proteins (RBPs) and erythrocyte binding proteins (EBPs). The Duffy receptor has long been established as a key determinant for P. vivax invasion. However, recently, the RBP protein PvRBP2b has been shown to bind to transferrin receptor, which is expressed on reticulocytes but lost on normocytes, implicating the ligand-receptor in the reticulocyte tropism of P. vivax. Furthermore there is increasing evidence for P. vivax growth and sexual development in reticulocyte-enriched tissues such as the bone marrow.
Topics: Animals; Host-Parasite Interactions; Humans; Malaria, Vivax; Plasmodium vivax; Protozoan Proteins; Reticulocytes; Tropism
PubMed: 30366310
DOI: 10.1016/j.mib.2018.10.002