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Frontiers in Immunology 2022Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both...
Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both autoantibodies (e.g. intrinsic factor (IFA) antibodies and anti parietal cell (PCA) antibodies and autoreactive T cells specific for IFA and the parietal cell proton pump ATPase. Iron deficient anemia (IDA) is a microcytic anemia and represents the most common cause of anemia worldwide. Our work aimed to investigate serum levels of several interleukins (IL) of the IL-20 cytokine subfamily in patients with PA, with IDA and in healthy subjects (HC). We compared serum levels of IL-19, IL-20, IL-26, IL-28A and IL-29 in 43 patients with PA and autoimmune gastritis, in 20 patients with IDA and no autoimmune gastritis, and in 47 HC. Furthermore, we analyzed the IL-19 cytokine production by gastric lamina propria mononuclear cells (LPMC) in eight patients with PA and four HC. We found that patients with PA have significantly higher serum levels of IL-19 (163.68 ± 75.96 pg/ml) than patients with IDA (35.49 ± 40.97 pg/ml; p<0.001) and healthy subjects (55.68 ± 36.75 pg/ml; p<0.001). Gastric LPMC from all PA patients were able to produce significantly higher levels of IL-19 (420.67 ± 68.14 pg/ml) than HC (53.69 ± 10.92 pg/ml) (<0.01). Altogether, our results indicate that IL-19 serum levels are significantly increased in patients with PA but not with IDA and that IL-19 is produced in the stomach of PA patients. These data open a new perspective on PA pathogenesis and suggest that IL-19 may represent a novel important tool for the management of patients with PA.
Topics: Anemia; Anemia, Pernicious; Autoantibodies; Cytokines; Gastritis; Humans; Interleukins
PubMed: 35479078
DOI: 10.3389/fimmu.2022.887256 -
Journal of Laboratory Physicians Dec 2021Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present...
Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present study was undertaken to analyze the value of duodenal biopsy in megaloblastic anemia and to correlate endoscopic findings with biopsy. As a secondary aim, the study has also analyzed the hematological profile and vitamin B and folate status of these patients. All the cases of megaloblastic anemia with bone marrow studies diagnosed at PSG Institute of Medical Sciences and Research during the two year period from January 2016 to December 2017 were retrieved. Clinical and laboratory findings (serum vitamin B and folate levels) and endoscopic findings were retrieved from hospital records of the patients. Duodenal biopsies of these patients reported in the histopathology department were retrieved and reviewed. Statistical analysis was done using SPSS software 20.0. There were 93 cases of megaloblastic anemia diagnosed on bone marrow biopsies. Tropical sprue was diagnosed in 49.5% of cases, followed by intraepithelial lymphocytosis (17.2%), peptic duodenitis (17.2%), and no significant pathology in 16% of cases. Pancytopenia was present in 54.8% of cases. Isolated vitamin B deficiency including low levels was present in 48.38% and folate deficiency was seen in 4.3% cases; 34.48% cases had both vitamin B and folate deficiency. The incidence of tropical sprue in megaloblastic anemia is 49.5% in the study. Duodenal biopsy is valuable in the work up of megaloblastic anemia, irrespective of the endoscopic changes in identifying the etiology.
PubMed: 34975246
DOI: 10.1055/s-0041-1730817 -
Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis.Science Advances Feb 2024Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as...
Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR), followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation. This is phenocopied by inhibition of folate metabolism using the inhibitor SHIN1, and by AICAR supplementation. Mechanistically, the metabolically driven differentiation is independent of mechanistic target of rapamycin complex 1 (mTORC1) and adenosine 5'-monophosphate-activated protein kinase (AMPK) and is instead mediated by protein kinase C. Our findings suggest that folate deprivation-induced premature differentiation of erythroid progenitor cells is a molecular etiology to folate deficiency-induced anemia.
Topics: Mice; Humans; Animals; Folic Acid; Cell Differentiation; Cell Line; Mechanistic Target of Rapamycin Complex 1; Purines
PubMed: 38295180
DOI: 10.1126/sciadv.adj9479 -
Experimental and Therapeutic Medicine Apr 2022Paget's disease of bone (PDB) is characterized by abnormal osteoclastic bone resorption with disorganized bone neo-formation, primarily affecting elderly (>55 years)...
Paget's disease of bone (PDB) is characterized by abnormal osteoclastic bone resorption with disorganized bone neo-formation, primarily affecting elderly (>55 years) patients. Although the majority of patients are asymptomatic, some patients may experience bone pain due to local periosteal involvement or osteoarthritic lesions in the spine; in addition, limb deformities may lead to secondary gait problems or degenerative joint changes. Anemia has an overall prevalence of 12-17% in elderly adults (>65 years old), with macrocytic anemia being the less common type. Megaloblastic anemia is a macrocytic anemia characterized by the presence of large, immature, nucleated cells (megaloblasts) in the blood, with the most common cause being a deficiency of folate and/or vitamin B12. We herein report the rare case of a 72-year-old male patient exhibiting both these conditions, with the aim of discussing the possible association between the two and, most importantly, the clinical management of the patient in a real-life setting over a period of 10 years. The patient was diagnosed based on clinical symptoms (bone pain), radiological imaging and specific laboratory tests, and received discontinuous courses of bisphosphonates and cyanocobalamin supplementation therapy, based mainly on aggravated symptomatology. A systematic literature review was also performed and revealed not only the scarcity of reports on similar cases, but also the mechanisms that may underlie the possible association of PDB with macrocytic anemia due to vitamin B12 deficiency in elderly patients.
PubMed: 35251335
DOI: 10.3892/etm.2022.11195 -
Frontiers in Genetics 2023Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may...
Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill. Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry. Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the gene. Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.
PubMed: 36999056
DOI: 10.3389/fgene.2023.1135267 -
Journal of Family Medicine and Primary... Feb 2021Pancytopenia is a triage of anemia, leukopenia, and thrombocytopenia. The etiology causing pancytopenia varies depending upon factors such as age, sex, occupation, and...
BACKGROUND
Pancytopenia is a triage of anemia, leukopenia, and thrombocytopenia. The etiology causing pancytopenia varies depending upon factors such as age, sex, occupation, and geographical distribution. Unfortunately, the major treatises of hematology have not given emphasis on the hemorrhagic manifestation of different etiologies causing pancytopenia.
OBJECTIVE
This observational study was carried out with the aim to identify hemorrhagic manifestation in patients with pancytopenia in eastern India.
DESIGN
This study was conducted over a period of two years at the Department of Medicine of a tertiary care teaching institute in eastern India. All the patients with features of anemia, thrombocytopenia, or leukopenia were screened for pancytopenia and a total of 214 cases were selected. Patients were divided into two groups as patients with age more than 14 years constitute group one and the patients less than 14 years constitute the second group. A detailed physical examination, hematological, and biochemical investigation was done to ascertain the hemorrhagic manifestations in pancytopenia patients.
RESULTS
In the groups, the most common cause of hemorrhagic manifestation in patients with pancytopenia was aplastic anemic, leukemia, myelodysplastic syndrome, and myelofibrosis. No bleeding manifestation was seen in patients with megaloblastic anemia, kala-azar, hypersplenism, and other causes of pancytopenia.
CONCLUSIONS
Patients with pancytopenia caused by aplastic anemia, acute leukemia, and myelodysplastic syndrome have more chances of bleeding manifestation as compared with pancytopenia caused by megaloblastic anemia, kala-azar, or hypersplenism.
PubMed: 34041080
DOI: 10.4103/jfmpc.jfmpc_1117_20 -
Nutrients Jun 2023Vitamin B (B) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine.... (Review)
Review
Vitamin B (B) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine. Methionine is an important donor of methyl groups for numerous biochemical reactions, including DNA synthesis and gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in B may cause neurological symptoms, including symptoms resembling diabetic neuropathy. Although extensively studied, the underlining molecular mechanism for the development of diabetic peripheral neuropathy (DPN) is still unclear. Most studies have found a contribution of oxidative stress in the development of DPN. Detailed immunohistochemical investigations in sural nerve biopsies obtained from diabetic patients with DPN point to an activation of inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting in increased oxidative stress. Similar results have been found in patients with B deficiency, indicating that the observed neural changes in patients with DPN might be caused by cellular B deficiency. Since novel results show that B exerts intrinsic antioxidative activity in vitro and in vivo, B may act as an intracellular, particularly as an intramitochondrial, antioxidant, independent from its classical, well-known cofactor function. These novel findings may provide a rationale for the use of B for the treatment of DPN, even in subclinical early states.
Topics: Humans; Vitamin B 12; Diabetic Neuropathies; Vitamin B 12 Deficiency; Antioxidants; Methionine; Vitamins; Diabetes Mellitus
PubMed: 37299560
DOI: 10.3390/nu15112597 -
International Journal of Clinical and... 2015The present study describes a case of an elderly patient that was hospitalized secondary to hypotension and delirium. Physical examination at admission revealed...
The present study describes a case of an elderly patient that was hospitalized secondary to hypotension and delirium. Physical examination at admission revealed bilateral positive Babinski's sign. Laboratory examination revealed severe anemia. Bone marrow examination showed megaloblastic changes of the granulocyte and erythroid series, as well as other dyshaematopoiesis. The conditions of the patient rapidly improved after vitamin B12 treatments. Because the clinical manifestations of megaloblastic anemia are complex, this disease is often misdiagnosed in the geriatric population. Bone marrow examinations can aid in the diagnosis of anemia, but the results from these tests cannot always differentiate the type of anemia. Clinical management of the disorder is reliant upon proper classification of the type of anemia. The prognosis of megaloblastic anemia is typically good and a simple regimen of folic acid and/or vitamin B12 is effective.
PubMed: 26770511
DOI: No ID Found -
Journal of Medicine and Life 2017To investigate the association between pernicious anemia and other autoimmune diseases.
OBJECTIVE
To investigate the association between pernicious anemia and other autoimmune diseases.
METHODS
This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome.
RESULTS
A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b.
CONCLUSION
We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.
Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Female; Humans; Male; Middle Aged; Polyendocrinopathies, Autoimmune; Retrospective Studies
PubMed: 29362601
DOI: No ID Found -
Cureus Nov 2023We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup...
We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup showed pancytopenia with severe macrocytic anemia, laboratory and blood smear features of hemolysis, low reticulocyte percentage and a negative direct Coombs test. B12 and folate levels were normal. As bone marrow aspirate was suggestive of megaloblastic anemia and upper endoscopy showed atrophic gastritis, we ordered homocysteine (elevated) and intrinsic factor (IF) antibodies (positive). The workup led to the diagnosis of pernicious anemia with spuriously normal B12 levels. Replacement therapy allowed a rapid recovery. We highlight that the presence of IF antibodies can interfere with the competitive binding assays commonly used to measure B12 levels.
PubMed: 38106734
DOI: 10.7759/cureus.48937