Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study.

Autor:	Goldis R; Department of Neurology, Sheba Medical Center, Ramat Gan, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Kaplan B; Institute of Hematology and Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel., Arad M; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Heart Failure Institute, Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel., Dispenzieri A; Division of Hematology, Mayo Clinic, Rochester, MN, USA., Dasari S; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Kukuy OL; Institute of Nephrology and Hypertension, Sheba Medical Center, Ramat Gan, Israel., Simon AJ; Institute of Hematology and Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel., Dori A; Department of Neurology, Sheba Medical Center, Ramat Gan, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Shavit-Stein E; Department of Neurology, Sheba Medical Center, Ramat Gan, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Ziv T; Smoler Protein Center, Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel., Murray D; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Kourelis T; Division of Hematology, Mayo Clinic, Rochester, MN, USA., Gertz MA; Division of Hematology, Mayo Clinic, Rochester, MN, USA., Dominissini D; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; The Genomics Unit, Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.; Wohl Institute of Translational Medicine, Sheba Medical Center, Ramat Gan, Israel., Magen H; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Multiple Myeloma Unit, Hematology Department, Sheba Medical Center, Ramat Gan, Israel., Muchtar E; Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Jazyk:	angličtina
Zdroj:	Clinical chemistry and laboratory medicine [Clin Chem Lab Med] 2023 Sep 26; Vol. 62 (3), pp. 464-471. Date of Electronic Publication: 2023 Sep 26 (Print Publication: 2024).
DOI:	10.1515/cclm-2023-0591
Abstrakt:	Objectives: Diagnosis of light chain amyloidosis (AL) requires demonstration of amyloid deposits in a tissue biopsy followed by appropriate typing. Previous studies demonstrated increased dimerization of monoclonal serum free light chains (FLCs) as a pathological feature of AL. To further examine the pathogenicity of FLC, we aimed at testing amino acid sequence homology between circulating and deposited light chains (LCs). Methods: Matched tissue biopsy and serum of 10 AL patients were subjected to tissue proteomic amyloid typing and nephelometric FLC assay, respectively. Serum FLC monomers (M) and dimers (D) were analyzed by Western blotting (WB) and mass spectrometry (MS). Results: WB of serum FLCs showed predominance of either κ or λ type, in agreement with the nephelometric assay data. Abnormal FLC M-D patterns typical of AL amyloidosis were demonstrated in 8 AL-λ patients and in one of two AL-κ patients: increased levels of monoclonal FLC dimers, high D/M ratio values of involved FLCs, and high ratios of involved to uninvolved dimeric FLCs. MS of serum FLC dimers showed predominant constant domain sequences, in concordance with the tissue proteomic amyloid typing. Most importantly, variable domain sequence homology between circulating and deposited LC species was demonstrated, mainly in AL-λ cases. Conclusions: This is the first study to demonstrate homology between circulating FLCs and tissue-deposited LCs in AL-λ amyloidosis. The applied methodology can facilitate studying the pathogenicity of circulating FLC dimers in AL amyloidosis. The study also highlights the potential of FLC monomer and dimer analysis as a non-invasive screening tool for this disease. (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
Databáze:	MEDLINE
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