A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia

Abstract

Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerises and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes leads to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research; however, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia.

Sickle Cell Disease Update: New Treatments and Challenging Nutritional Interventions

“…Several reviews have revealed a solid connection between oxidative stress, inflammation, the immune response, and the pathogenesis of SCD, enhancing the role of the dominant natural immune system [ 205 , 206 ].…”

“…Substantial oxidative stress is a prominent contributor to SCD due to a disproportionate yield of reactive oxygen species compared with the ability of antioxidant agents, including enzymes such as SODs, catalase, and glutathione peroxidase, to counteract them. Multiple inflammatory pathways are stimulated in a chain reaction involving sickle cell redox balance, hemolysis, vasculopathy, and regulation in the immune response [ 205 ].…”

Chemotherapy-Induced Anemia in Adults Incidence and Treatment

“…The precursors decrease the expression of the EPO receptor, hence impeding the generation of EPO [53]. Furthermore, IL-1 and other proinflammatory cytokines have been linked to the activation of macrophages for erythrophagocytosis, which causes the early erythrocyte destruction and reduced erythrocyte survival [54].…”

Ferroptosis as an emerging target in sickle cell disease

“…Additionally, oxidative modifications in sickle RBCs, caused by oxidants like nitric oxide (NO•) and ONOO − released during hemolysis, lead to further complications including vaso-occlusion, renal damage, and continued hemolysis ( Nader et al, 2020 , Jutant et al, 2021 , Wang and Zennadi, 2021 , Aboderin et al, 2023 ).…”