title: Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4.
abstract: Autoantibodies against SCLC-associated neuronal antigen ELAVL4 (HuD) have been linked to smaller tumors and improved survival, but the antigenic epitope and mechanism of autoimmunity have never been solved. We report that recombinant human ELAVL4 protein incubated under physiological conditions acquires isoaspartylation, a type of immunogenic protein damage. Specifically, the N-terminal region of ELAVL4, previously implicated in SCLC-associated autoimmunity, undergoes isoaspartylation in vitro, is recognized by sera from anti-ELAVL4 positive SCLC patients and is highly immunogenic in subcutaneously injected mice and in vitro stimulated human lymphocytes. Our data suggest that isoaspartylated ELAVL4 is the trigger for the SCLC-associated anti-ELAVL4 autoimmune response.
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Pulido
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Meleeneh Kazarian
authors.initials: MK
authors.lastname: DerHartunian
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA.
authors.forename: Zhenxia
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Chung
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Kang
authors.affiliation: Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Woodham
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tsou
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Rinse
authors.initials: R
authors.lastname: Klooster
authors.affiliation: Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
authors.affiliation: Department of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Liu
authors.affiliation: Department of Neurology, Leiden University, Leiden, the Netherlands.
authors.forename: Jan J G M
authors.initials: JJGM
authors.lastname: Verschuuren
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA.
authors.forename: Dana W
authors.initials: DW
authors.lastname: Aswad
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Ite A
authors.initials: IA
authors.lastname: Laird-Offringa
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D000067779:ELAV-Like Protein 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human
keywords: Autoimmunity; Isoaspartylation; SCLC; Small cell lung cancer