AL amyloidosis enhances development of amyloid A amyloidosis

Conflicts of interest: none declared. Sir, In the April issue of this journal, Rekhtman et al. describe an interesting case of a patient with concomitant AL (also referred to as primary or myeloma‐associated amyloidosis) and amyloid A (AA) amyloidosis.1 The authors state that ‘the pathogenesis of dual amyloidosis is not clear nor is the relationship of dual deposits with rapid progression’. However, our recent advances in the knowledge of the pathogenesis of amyloidosis may explain both enigmas. The amyloidoses constitute a group of disorders that are characterized by deposition of protein fibrils in organs and tissues leading to organ dysfunction.2 The fibrils are aggregates of a precursor protein that has a typical β‐pleated‐sheet conformation. So far at least 23 different precursor proteins have been identified that can aggregate into fibrils, including Aβ peptide in Alzheimer plaques and β2 microglobulin in haemodialysis‐associated amyloidosis.3 Amyloidosis develops when the precursor protein is over‐expressed [e.g. increased expression of acute phase protein serum amyloid A protein (SAA) during inflammation in AA amyloidosis] or when a mutation in a constitutively expressed protein leads to a greater tendency to aggregate (e.g. in familial ATTR amyloidosis). In type AA amyloidosis SAA has to be proteolytically cleaved into AA amyloid fragments before these can be incorporated into fibrils.