Sickle Cell Anemia and Inflammation: A Review of Stones and Landmarks Paving the Road in the Last 25 Years

Area of Science:

• Genetics
• Molecular Biology
• Hematology

Background:

• Sickle cell disease (SCD) was historically viewed as a straightforward Mendelian genetic disorder, focusing on HbS allele identification.
• The clinical variability of SCD, even in homozygous individuals, suggests factors beyond the primary mutation are involved.
• Chronic inflammation accompanying erythrocyte sickling is now recognized as a critical aspect of SCD pathogenesis.

Purpose of the Study:

• To revisit early evidence of inflammation in SCD.
• To review advancements in understanding SCD inflammation over the past 25 years.
• To highlight SCD's historical significance in genetic disease research and molecular biology.

Main Methods:

• Literature review of early studies on inflammation in SCD.
• Analysis of scientific literature from the last 25 years focusing on SCD pathogenesis.
• Historical overview of SCD's role in the advancement of genetic disease understanding and treatment.

Main Results:

• SCD is confirmed as homozygosis for the HbS variant, but this alone doesn't explain its complex clinical spectrum.
• Chronic inflammation is a significant and integral feature of SCD, contributing to disease severity.
• SCD was the first genetic disease with an identified causal mutation and the first approved for genome editing therapy.

Conclusions:

• SCD's understanding has evolved from a simple genetic trait to a complex inflammatory disease.
• The disease serves as a pivotal model in molecular biology, demonstrating significant progress in genetic research and therapeutic interventions like genome editing.
• Further research into the inflammatory pathways of SCD is crucial for improving patient outcomes.