Pathomechanisms of Immunological Disturbances in β-Thalassemia

Abstract

Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain synthesis. Patients with β-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in β-thalassemia patients is associated with the interplay of several complex biological processes. β-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in β-thalassemia patients may enable the designing of appropriate therapies for this group of patients.

Case report: Successful outcome of treatment using rituximab in an adult patient with refractory minimal change disease and β-thalassemia complicating autoimmune hemolytic anemia

“…However, there is no evidence to support whether the variant of the Codons 41/42 (−TTCT) BETA 0 in HBB of this patient is an inherited or sporadic variation as she has no siblings and her parents refused genetic testing. The favorable effect of RTX on the improvement of anemia in this patient is speculated to be related to β-thalassemia itself, β-thalassemia may directly lead to sustained immune stimulation ( 26 , 27 ). The research focused on AIHA in patients with β-thalassemia is limited.…”

“…The imbalance of HGB chain synthesis in erythrocytes results in an excess of released α-globulin chains, which precipitate in precursors of erythrocytes and lead to structural changes in the cell membrane ( 28 ). The presence of these abnormal erythrocytes results in the continued activation of monocytes responsible for immune clearance, alterations of T and B lymphocytes, etc., that possibly be involved in the pathogenesis of AIHA ( 27 , 29 ). Alloimmunization in patients with β-thalassemia major is usually associated with multiple blood transfusion ( 27 , 28 ).…”

“…The presence of these abnormal erythrocytes results in the continued activation of monocytes responsible for immune clearance, alterations of T and B lymphocytes, etc., that possibly be involved in the pathogenesis of AIHA ( 27 , 29 ). Alloimmunization in patients with β-thalassemia major is usually associated with multiple blood transfusion ( 27 , 28 ). AIHA in the patient reported here was not transfusion dependent.…”

Thalassemia and Nanotheragnostics: Advanced Approaches for Diagnosis and Treatment

“…The unbalanced production of these α-globin and β-globin chains is the main pathophysiological mechanism involved in the development of thalassemia. The decreased or abnormal synthesis of one globin chain leads to the toxic accumulation of the other globin chains, which causes a drastic reduction in functional hemoglobin [ 24 , 25 , 26 , 27 ]. Moreover, the excessive globin chains, after aggregating, may form reactive oxygen species and damage the red blood cell membranes, which may lead to hemolysis and abnormal erythroid maturation [ 3 , 27 ].…”

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

“…The immunologic consequences of alloimmunization have been explored from humoral allosensitization to the impact of transfusion on cellular immune function (Vichinsky et al, 2014, Dhawan et al, 2014. Increased immunoglobulin production, insufficient complement system activity, reduced opsonization, and granulocyte phagocytosis have all been recorded as immunological abnormalities (Sinniah and Yadav, 1981, Tovo et al, 1981, Gluba-Brzózka et al, 2021. There is also evidence that thalassemia has an effect on the cellmediated immune response and lymphocyte subsets (Javad et al, 2011).…”