Immunoglobulin light chain (kappa and lambda) (FLC)

Misfolded kappa (κ) and lambda (λ) immunoglobulin light chains are the pathological drivers of AL amyloidosis, a systemic disorder characterized by the extracellular deposition of amyloid fibrils (Merlini et al., 2011). These proteins are produced by an underlying plasma cell dyscrasia and possess structural instabilities that lead to their misfolding into toxic soluble oligomers and insoluble fibrils (Shi et al., 2010). The deposition of these fibrils in vital organs, most commonly the heart and kidneys, causes progressive organ damage and failure (Dispenzieri et al., 2012). Beyond physical deposition, soluble misfolded light chains exert direct proteotoxic effects on tissues, particularly cardiomyocytes, contributing to rapid cardiac dysfunction (Shi et al., 2010). Therapeutic interventions targeting these misfolded species include monoclonal antibodies like birtamimab and anselamimab, which are designed to bind specific neoepitopes exposed only on the misfolded or aggregated forms (Gertz et al., 2023; Edwards et al., 2021). These drugs work by neutralizing toxic soluble aggregates and promoting the clearance of existing amyloid deposits through macrophage-mediated phagocytosis (Edwards et al., 2021). By addressing the misfolded protein directly, these therapies aim to improve organ function and survival outcomes beyond what is achieved by standard chemotherapy alone (Gertz et al., 2023).

Other names

Misfolded light chainsAmyloidogenic light chainsFree light chainsAL proteinMonoclonal light chains

Neutralization of soluble toxic aggregates and opsonization of amyloid fibrils to promote phagocytic clearance.