Organ-specific (localized) synthesis of Ig light chain amyloid

Ig amyloidosis is usually a systemic disease with multisystem involvement. However, in a significant number of cases amyloid deposition is limited to one specific organ. It has not been determined if the Ig light chain (LC) a myloid precursor protein in localized amyloidosis is synthesized by circula ting plasma cells with targeting of the amyloid fibril-forming process to o ne specific organ, or whether the synthesis of Ig LC and fibril formation o ccurs entirely as a localized process. In the present study local synthesis of an amyloid fibril precursor LC was investigated, Amyloid fibrils were i solated from a ureter that was obstructed by extensive infiltration of the wall with amyloid, Amino acid sequence analysis of the isolated fibril subu nit protein proved it to be derived from a lambda(mu) Ig LC, Plasma cells w ithin the lesion stained positively with labeled anti-lambda Ab and by in s itu hybridization using an oligonucleotide probe specific for lambda-LC mRN A. RT-PCR of mRNa extracted from the tumor and direct DNA sequencing gave t he nucleotide sequence coding specifically for the lambda(mu) amyloid subun it protein, thus confirming local synthesis of the LC protein.