Application of monoclonal anti-idiotypes in the study of AL amyloidosis: Therapeutic implications

Vittorio Bellotti, Monica Stoppini, Vittorio Perfetti, Irene Zorzoli, Gabriella Marinone, Anna Maggi, Rosangela Invernizzi, Eloisa Arbustini, Giampaolo Merlini

Research output: Contribution to journalArticle

Abstract

A monoclonal anti-idiotype antibody (IgGlk MAb 3B11D4) has been raised against the λchain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylated λchain monomers, nor the 15-to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of the λ chain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.

Original languageEnglish
Pages (from-to)365-371
Number of pages7
JournalRenal Failure
Volume15
Issue number3
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Nephrology
  • Critical Care and Intensive Care Medicine

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    Bellotti, V., Stoppini, M., Perfetti, V., Zorzoli, I., Marinone, G., Maggi, A., Invernizzi, R., Arbustini, E., & Merlini, G. (1993). Application of monoclonal anti-idiotypes in the study of AL amyloidosis: Therapeutic implications. Renal Failure, 15(3), 365-371. https://doi.org/10.3109/08860229309054946