Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

被引：16

作者：

Al Kindi, Mahmood A. ^{[1
,2
]}

Chataway, Tim K. ^{[3
]}

Gilada, George A. ^{[1
,2
]}

Jackson, Michael W. ^{[1
,2
]}

Goldblatt, Fiona M. ^{[1
,2
]}

Walker, Jenny G. ^{[1
,2
]}

Colella, Alex D. ^{[3
]}

Gordon, Tom P. ^{[1
,2
]}

机构：

[1] Flinders Med Ctr, Dept Immunol, Bedford Pk, SA 5042, Australia

[2] Flinders Univ S Australia, SA Pathol, Bedford Pk, SA 5042, Australia

[3] Flinders Univ S Australia, Flinders Prote Facil, Bedford Pk, SA, Australia

来源：

JOURNAL OF AUTOIMMUNITY | 2015年 / 57卷

基金：

英国医学研究理事会;

关键词：

Sm autoantigen; Systemic lupus erythematosus; Public clonotypes; Mass spectrometry; PRIMARY SJOGRENS-SYNDROME; ANTI-SM; IMMUNE-COMPLEXES; GENE USAGE; AUTOIMMUNITY; INTERFERON; RESPONSES;

D O I：

10.1016/j.jaut.2014.12.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)-region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69 H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and individual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region diversity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：77 / 81

页数：5

共 24 条

[1]

Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis [J].