Cell-Free Mitochondrial DNA as a Damage-Associated Molecular Pattern and Candidate Biomarker in Sickle Cell Disease Vaso-Occlusive Crisis: A Scoping Review

Sickle cell disease (SCD) is defined by consistent hemolysis, recurrent vaso-occlusive crises and continual low-grade inflammation fueled by damage-associated molecular patterns (DAMPs) produced by damaged erythrocytes. Recently, cf-mtDNA has been named as one such DAMP, able to activate neutrophil extracellular trap formation through cGAS-STING-TBK1 pathway. However, evidence on its origin, mechanisms and clinical utility is minimal, mechanistically fragmented and excessively produced outside sub-Saharan Africa, which suffers the greatest portion of the global SCD burden. This review is being prepared to map the level, range and nature of the arising evidence base on cf-mtDNA as a damage-associated molecular pattern and candidate biomarker in SCD vaso-occlusive crisis, and to point out crucial gaps (with a focus on sub-Saharan Africa) to inform future primary studies.