Impact of persistent antigenic challenges and splenectomy on immune cells in β-Thalassemic patients.

Authors

  • Sonia Elia Ishaq Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
  • Taban Kamal Rasheed College of Agricultural engineering Science, Salahaddin University- Erbil, Kurdistan Region, Iraq
  • Dara K. Mohammad 1College of Agricultural engineering Science, Salahaddin University- Erbil, Kurdistan Region, Iraq. 2Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Huddinge, Sweden.

DOI:

https://doi.org/10.21271/ZJPAS.34.4.13

Keywords:

Thalassemia, Macrophage, GM-CSF, Neopterin

Abstract

Infection is common in thalassemia patients and is one of the leading causes of death. It's still unclear why these individuals are so sensitive to infection. There is strong evidence that a deficiency in the functioning of phagocytic cells plays a key role in the weakened resistance to pathogenic bacteria. The purpose of this study was to investigate the function of phagocytic cells by comparing the serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and Neopterin in thalassemia patients to healthy people. The study included 50 thalassemia patients and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was applied to estimate the serum levels of GM-CSF and Neopterin. Serum levels of GM-CSF were significantly elevated in thalassemia patients when compared to healthy people (p < 0.05), while serum levels of Neopterin showed no significant change between thalassemia patients and healthy controls. Both serum levels of GM-CSF and Neopterin showed no significant difference between Splenectomized and healthy controls. Total leukocyte counts, lymphocytes, MID (monocytes), platelets, and RBC were all significantly higher in thalassemia patients compared to healthy controls. But, granulocyte counts showed no significant difference between the thalassemia patients and the healthy controls. On the other hand, total leukocytes, monocytes, lymphocytes and platelets counts were significantly raised in splenectomized patients when compared to healthy controls and non-splenectomized patients, respectively. We came to the conclusion that thalassemia patients have a high immune cell count, which is most likely due to the antigenic difficulties posed by blood transfusions. On the other hand, these patients have an impaired immune system.

References

AL‐AWADHI, A., ALFADHLI, S., AL‐KHALDI, D., BORHAMA, M. & BORUSLY, M. 2010. Investigation of the distribution of lymphocyte subsets and zinc levels in multitransfused β‐thalassemia major patients. International journal of laboratory hematology, 32, 191-196.

ANGASTINIOTIS, M. & LOBITZ, S. 2019. Thalassemias: an overview. International Journal of Neonatal Screening, 5, 16.

ASADOV, C. D. 2014. Immunologic abnormalities in β-thalassemia. Journal of Blood Disorders Transfusion, 5, 1-5.

CUNNINGHAM, M. J., MACKLIN, E. A., NEUFELD, E. J., COHEN, A. R. & NETWORK, T. C. R. 2004. Complications of β-thalassemia major in North America. Blood, 104, 34-39.

DHAWAN, H. K., KUMAWAT, V., MARWAHA, N., SHARMA, R. R., SACHDEV, S., BANSAL, D., MARWAHA, R. K. & ARORA, S. 2014. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients. Asian journal of transfusion science, 8, 84.

FARMAKIS, D., GIAKOUMIS, A., AESSOPOS, A. & POLYMEROPOULOS, E. 2003. Pathogenetic aspects of immune deficiency associated with ß thalassemia. Medical Science Monitor, 9, RA19-RA22.

FLINT, J., HARDING, R., BOYCE, A. & CLEGG, J. 1998. The population genetics of the hemoglobinopathies, Bailliere's Clin. Hematol.

GHAFFARI, J., VAHIDSHAHI, K., KOSARYAN, M., PARVINNEJAD, N., MAHDAVI, M. & KARAMI, H. 2008. Nitroblue tetrazolium test in patients with beta-thalassemia major. Saudi Med J, 29, 1601-5.

GHAFFARI, J., VAHIDSHAHI, K., KOSARYAN, M., SOLTANTOOYEH, Z. & MOHAMADI, M. 2011. Humoral immune system state in ß thalassemia major. Med Glas (Zenica), 8, 192-6.

GHARAGOZLOO, M., KARIMI, M. & AMIRGHOFRAN, Z. 2009. Double-faced cell-mediated immunity in β-thalassemia major: stimulated phenotype versus suppressed activity. Annals of hematology, 88, 21-27.

GINZBURG, Y. & RIVELLA, S. 2011. β-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood, The Journal of the American Society of Hematology, 118, 4321-4330.

GLUBA-BRZÓZKA, A., FRANCZYK, B., RYSZ-GÓRZYŃSKA, M., ROKICKI, R., KOZIARSKA-ROŚCISZEWSKA, M. & RYSZ, J. 2021. Pathomechanisms of Immunological Disturbances in β-Thalassemia. International Journal of Molecular Sciences, 22, 9677.

HIGGS, D., THEIN, S. & WOODS, W. 2001. The molecular pathology of the thalassaemias. The thalassaemia syndromes. 4th ed. Oxford, England: Blackwell Science, 133-91.

HIRATA, Y., EGEA, L., DANN, S. M., ECKMANN, L. & KAGNOFF, M. F. 2010. GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen. Cell host & microbe, 7, 151-163.

HOFFMANN, G., WIRLEITNER, B. & FUCHS, D. 2003. Potential role of immune system activation-associated production of neopterin derivatives in humans. Inflammation Research, 52, 313-321.

JAVAD, G., SAEID, A. & MOHAMMADMEHDI, N. 2011. Thalassemia and immune system dysfunction-review article. Int J Curr Res, 3, 105-108.

KATTAMIS, A., FORNI, G. L., AYDINOK, Y. & VIPRAKASIT, V. 2020. Changing patterns in the epidemiology of β‐thalassemia. European Journal of Haematology, 105, 692-703.

LEECHAROENKIAT, K., LITHANATUDOM, P., SORNJAI, W. & SMITH, D. R. 2016. Iron dysregulation in beta-thalassemia. Asian Pacific journal of tropical medicine, 9, 1035-1043.

LEVINE, A. M., REED, J. A., KURAK, K. E., CIANCIOLO, E. & WHITSETT, J. A. 1999. GM-CSF–deficient mice are susceptible to pulmonary group B streptococcal infection. The Journal of clinical investigation, 103, 563-569.

LI, B.-Z., YE, Q.-L., XU, W.-D., LI, J.-H., YE, D.-Q. & XU, Y. 2013. GM-CSF alters dendritic cells in autoimmune diseases. Autoimmunity, 46, 409-418.

MCBRIDE, J., DACIE, J. & SHAPLEY, R. 1968. The effect of splenectomy on the leucocyte count. British journal of haematology, 14, 225-231.

MENCACCI, A., CENCI, E., BOELAERT, J. R., BUCCI, P., MOSCI, P., D'OSTIANI, C. F., BISTONI, F. & ROMANI, L. 1997. Iron overload alters innate and T helper cell responses to Candida albicans in mice. The Journal of infectious diseases, 175, 1467-1476.

MODELL, B. & BERDOUKAS, V. 1983. The clinical approach to thalassaemia. GRUNE AND STRATTON, NEW YORK, NY(USA). 1983.

O'NEAL JR, H. R., NIVEN, A. S. & KARAM, G. H. 2016. Critical illness in patients with asplenia. Chest, 150, 1394-1402.

OBEID, S. F., AL-A’ARAJI, S. B., MATTI, B. F. & FAWZI, H. A. 2018. Neopterin And Interferon-Gamma as Immune Response Markers In Beta-Thalassemia Major Patients. Asian J Pharm Clin Res, 11, 192-194.

OMARA, F. O. & BLAKLEY, B. R. 1994. The effects of iron deficiency and iron overload on cell-mediated immunity in the mouse. British Journal of Nutrition, 72, 899-909.

OXENKRUG, G., TUCKER, K., REQUINTINA, P. & SUMMERGRAD, P. 2011. Neopterin, a marker of interferon-gamma-inducible inflammation, correlates with pyridoxal-5′-phosphate, waist circumference, HDL-cholesterol, insulin resistance and mortality risk in adult Boston community dwellers of Puerto Rican origin. American journal of neuroprotection and neuroregeneration, 3, 48-52.

PAINE, R., PRESTON, A. M., WILCOXEN, S., JIN, H., SIU, B. B., MORRIS, S. B., REED, J. A., ROSS, G., WHITSETT, J. A. & BECK, J. M. 2000. Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice. The Journal of Immunology, 164, 2602-2609.

PHILIP, J. & JAIN, N. 2014. Resolution of alloimmunization and refractory autoimmune hemolytic anemia in a multi-transfused beta-thalassemia major patient. Asian Journal of Transfusion Science, 8, 128.

POOTRAKUL, P., KITCHAROEN, K., YANSUKON, P., WASI, P., FUCHAROEN, S., CHAROENLARP, P., BRITTENHAM, G., PIPPARD, M. J. & FINCH, C. A. 1988. The effect of erythroid hyperplasia on iron balance.

SARI, T. T., GATOT, D., AKIB, A. A., BARDOSONO, S., HADINEGORO, S. R., HARAHAP, A. R. & IDJRADINATA, P. S. 2016. Immune response of thalassemia major patients in Indonesia with and without splenectomy. Acta Medica Indonesiana, 46.

SHAPOURI‐MOGHADDAM, A., MOHAMMADIAN, S., VAZINI, H., TAGHADOSI, M., ESMAEILI, S. A., MARDANI, F., SEIFI, B., MOHAMMADI, A., AFSHARI, J. T. & SAHEBKAR, A. 2018. Macrophage plasticity, polarization, and function in health and disease. Journal of cellular physiology, 233, 6425-6440.

SINNIAH, D. & YADAV, M. 1981. Elevated IgG and decreased complement component C3 and factor B in B‐thalassaemia major. Acta Paediatrica, 70, 547-550.

SINWAR, P. D. 2014. Overwhelming post splenectomy infection syndrome–review study. International journal of surgery, 12, 1314-1316.

SUCHER, R., SCHROECKSNADEL, K., WEISS, G., MARGREITER, R., FUCHS, D. & BRANDACHER, G. 2010. Neopterin, a prognostic marker in human malignancies. Cancer letters, 287, 13-22.

TOVO, P. A., MINIERO, R., BARBERA, C., SACCHETTI, L. & SAITTA, M. 1981. Serum immunoglobulins in homozygous β-thalassemia. Acta haematologica, 65, 21-25.

UD-NAEN, S., TANSIT, T., KANISTANON, D., CHAIPRASERT, A., WANACHIWANAWIN, W. & SRINOULPRASERT, Y. 2019. Defective cytokine production from monocytes/macrophages of E-beta thalassemia patients in response to Pythium insidiosum infection. Immunobiology, 224, 427-432.

VICHINSKY, E., NEUMAYR, L., TRIMBLE, S., GIARDINA, P. J., COHEN, A. R., COATES, T., BOUDREAUX, J., NEUFELD, E. J., KENNEY, K. & GRANT, A. 2014. Transfusion complications in thalassemia patients: a report from the C enters for D isease C ontrol and P revention (CME). Transfusion, 54, 972-981.

WIENER, E. 2003. Impaired phagocyte antibacterial effector functions in β-thalassemia: A likely factor in the increased susceptibility to bacterial infections. Hematology, 8, 35-40.

ZHAN, Y., XU, Y. & LEW, A. M. 2012. The regulation of the development and function of dendritic cell subsets by GM-CSF: more than a hematopoietic growth factor. Molecular immunology, 52, 30-37.

Published

2022-08-15

How to Cite

Sonia Elia Ishaq, Taban Kamal Rasheed, & Dara K. Mohammad. (2022). Impact of persistent antigenic challenges and splenectomy on immune cells in β-Thalassemic patients. Zanco Journal of Pure and Applied Sciences, 34(4), 116–122. https://doi.org/10.21271/ZJPAS.34.4.13

Issue

Section

Biology, Chemistry and Medical Researches