title: Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining.
abstract: AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.
authors.affiliation: Department of Nephrology, Yokohama Rosai Hospital, Kanagawa, Japan; Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan; Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Manabe
authors.affiliation: Department of Nephrology, Yokohama Rosai Hospital, Kanagawa, Japan.
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Nagano, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Yazaki
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.affiliation: Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. Electronic address: nagatam@md.tsukuba.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D007668:Kidney / Q000737:chemistry / Q000473:pathology*; D007674:Kidney Diseases / Q000150:complications / Q000175:diagnosis*
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: AH amyloidosis; Immunoglobulin heavy-chain amyloidosis; epitope; immunofluorescence staining; liquid chromatography–tandem mass spectrometry (LC-MS/MS); monoclonal gammopathy of renal significance (MGRS); truncated immunoglobulin