title: Physiological IgM class catalytic antibodies selective for transthyretin amyloid.
abstract: Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function.
authors.affiliation: From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Planque
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara
authors.forename: Sari
authors.initials: S
authors.lastname: Sonoda
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yukie
authors.initials: Y
authors.lastname: Mitsuda
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Massey
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Primmer
authors.forename: Brian
authors.initials: B
authors.lastname: O'Nuallain
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
mesh_terms: D000328:Adult; D000682:Amyloid / Q000276:immunology / Q000378:metabolism*; D017151:Antibodies, Catalytic / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity / Q000276:immunology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011228:Prealbumin / Q000276:immunology / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D000682:Amyloid; D017151:Antibodies, Catalytic; D007075:Immunoglobulin M; D011228:Prealbumin
keywords: Aging; Amyloid; Amyloidosis; Antibodies; Catalytic Antibody; Innate Immunity; Protein Evolution; Superantigen; Transthyretin