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      Evaluation of immune system in patients with transfusion‐dependent beta‐thalassemia in Rasoul‐e‐Akram Hospital in 2021: A descriptive cross‐sectional study

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          Abstract

          Background and aims

          Thalassemia syndromes are the most common hemoglobinopathy globally related to blood transfusion and iron overload in the body. Splenectomy, excessive iron overload, and repeated exposure to antigens in blood transfusions can cause severe damage to the patient's immune system making the patient prone to frequent infection. This study evaluates the immune system status and infection rate in beta‐thalassemia major patients receiving iron chelators.

          Methods

          This descriptive cross‐sectional study was performed in Rasoul‐e‐Akram Hospital on patients with a beta‐thalassemia major who had iron overload due to frequent blood transfusions. The percentage of lymphocyte markers was determined by flow cytometry. Serum levels of immunoglobin were measured by nephelometric assay. Also, Nitro blue tetrazolium and dihydrorhodamine assays were used to evaluate the phagocytic function.

          Results

          Of the 106 patients participating in this study, 59 (55.7%) and 47 (44.3%) are male and female, respectively. The mean age ± SD of participants was 24.7 ± 12.1 years with 4 to 55 years. There was no significant correlation between sex, the C3 and C4 complements, the lymphocyte markers, and the immunoglobulin levels. Furthermore, all of these variables increased significantly over 30 ( p < 0.05). Moreover, there was a strong positive correlation between splenectomy and IgG immunoglobulin ( p < 0.001) and CD16 ( p = 0.005) lymphocyte marker.

          Conclusion

          Iron chelator agents effectively improve patients' immune system with thalassemia major. The increase in IgG and IgM immunoglobulins levels is due to frequent blood transfusions, which stimulate the immune system.

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          Most cited references33

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          Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine.

          Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications were analyzed. Survival after the first decade was studied for 977 patients born since 1960 whereas survival since birth and complication appearance was studied for the 720 patients born after 1970. Better survival was demonstrated for patients born in more recent years (p<0.00005) and for females (p=0.0003); 68% of the patients are alive at the age of 35 years. In the entire population 67% of the deaths were due to heart disease. There was a significant association between birth cohort and complication-free survival (p<0.0005). The prevalence of complications was: heart failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes 6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were associated with a lower probability of heart failure (hazard ratio =3.35, p<0.005) and with prolonged survival (hazard ratio = 2.45, p<0.005), using a cut-off as low as 1,000 ng/mL. Survival and complication-free survival of patients with thalassemia major continue to improve, especially for female patients born shortly before or after the availability of iron chelation.
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            Effects of iron overload on the immune system.

            Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.
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              Cardiac status in well-treated patients with thalassemia major.

              To assess cardiac status in a large group of patients with thalassemia major who had been treated in a standard way since their early infancy with intensive transfusions and deferoxamine chelation therapy and who had good compliance with this regimen. We assessed clinically and echocardiographically 202 thalassemia major patients aged 27.3 +/- 6.3 yr and 75 age and sex-matched healthy controls. Overt cardiac disease was encountered in 14 patients (6.9%), including 5 (2.5%) with congestive heart failure, aged 26-37 yr, and 9 with systolic left ventricular (LV) dysfunction, aged 23-37 yr. Ten patients (5.0%) had a history of pericarditis. Left atrial and LV diameters, LV mass and cardiac output were significantly higher in patients than in controls, while peripheral resistance and LV afterload were significantly lower. Relative LV wall thickness did not differ between patients and controls, but it was significantly lower in patients with overt cardiac disease compared to those without (P < 0.05). Restrictive LV filling was observed in 37.6% of patients and was significantly more frequent in cases with overt cardiac disease (P < 0.01). Pulmonary hypertension was practically absent. Hematological parameters and pulmonary artery pressure levels were not independently associated with the presence of overt cardiac disease. Strict lifelong adherence to the standard transfusion and deferoxamine therapy reduces considerably the occurrence of heart failure, LV dysfunction and pericarditis, prevents early heart failure and pulmonary hypertension, but does not eliminate completely cardiac disease in patients with thalassemia major.
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                Author and article information

                Contributors
                Pooya1375@yahoo.com
                Faranoush.m@iums.ac.ir
                Journal
                Health Sci Rep
                Health Sci Rep
                10.1002/(ISSN)2398-8835
                HSR2
                Health Science Reports
                John Wiley and Sons Inc. (Hoboken )
                2398-8835
                03 October 2022
                November 2022
                : 5
                : 6 ( doiID: 10.1002/hsr2.v5.6 )
                : e871
                Affiliations
                [ 1 ] Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran
                [ 2 ] Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering University of Tehran Tehran Iran
                [ 3 ] Department of Otolaryngology, Head & Neck Surgery, Taleghani Hospital Shahid Beheshti University of Medical Sciences Tehran Iran
                [ 4 ] Department of Medical Education Semnan University of Medical Sciences Semnan Iran
                [ 5 ] Cardio‐Oncology Research Center, Rajaie Cardiovascular Medical & Research Center Iran University of Medical Sciences Tehran Iran
                Author notes
                [*] [* ] Correspondence Pooya Faranoush and Mohammad Faranoush, Pediatric Growth and Development Research center, Institute of Endocrinology, Iran University of Medical Sciences, Tehran, Iran. 

                Email: Pooya1375@ 123456yahoo.com and Faranoush.m@ 123456iums.ac.ir

                Author information
                http://orcid.org/0000-0001-9329-6426
                http://orcid.org/0000-0002-2775-2347
                Article
                HSR2871
                10.1002/hsr2.871
                9528955
                36210881
                e3667845-4d5d-4068-baef-279dd6330f6a
                © 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 September 2022
                : 13 June 2022
                : 15 September 2022
                Page count
                Figures: 5, Tables: 0, Pages: 8, Words: 3884
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                November 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.9 mode:remove_FC converted:03.10.2022

                cellular immunity,humoral immunity,iron chelators agents,phagocytosis,thalassemia major

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