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Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis

Sokolove, Jeremy ; Bromberg, Reuven ; Deane, Kevin D ; Lahey, Lauren J ; Derber, Lezlie A ; Chandra, Piyanka E ; Edison, Jess D ; Gilliland, William R ; Tibshirani, Robert J ; Norris, Jill M ; Holers, V Michael ; Robinson, William H Matloubian, Mehrdad

PloS one, 2012-05, Vol.7 (5), p.e35296-e35296 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis
Autor: Sokolove, Jeremy ; Bromberg, Reuven ; Deane, Kevin D ; Lahey, Lauren J ; Derber, Lezlie A ; Chandra, Piyanka E ; Edison, Jess D ; Gilliland, William R ; Tibshirani, Robert J ; Norris, Jill M ; Holers, V Michael ; Robinson, William H
Matloubian, Mehrdad
Assuntos: Accumulation ; Adult ; Antibodies ; Antigenic determinants ; Arthritis ; Arthritis, Rheumatoid - blood ; Arthritis, Rheumatoid - diagnosis ; Arthritis, Rheumatoid - immunology ; Autoantibodies ; Autoantibodies - blood ; Autoantibodies - immunology ; Autoantigens - immunology ; Autoimmunity ; B cells ; Biology ; Biomarkers ; Biomarkers - blood ; Biomedical research ; Case-Control Studies ; Citrulline ; Classification ; Collaboration ; College campuses ; Correlation ; Cytokines ; Cytokines - blood ; Cytokines - immunology ; Development and progression ; Disease Progression ; DNA binding proteins ; Epitopes ; Epitopes - immunology ; Expansion ; Female ; Fibrin ; Fibrinogen ; Histones ; Human subjects ; Humans ; Immunity ; Immunoglobulins ; Immunologic factors ; Inflammation ; Interferon ; Interleukin 12 ; Interleukin 6 ; Male ; Medicine ; Middle Aged ; Multiplexing ; Peptides, Cyclic - immunology ; Prognosis ; Proteins ; Rheumatism ; Rheumatoid arthritis ; Rheumatology ; Tumor necrosis factor-α ; World population ; Young Adult ; γ-Interferon
É parte de: PloS one, 2012-05, Vol.7 (5), p.e35296-e35296
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: JS RB KDD LAD JDE WRG JMN VMH WHR. Performed the experiments: JS RB LJL PEC RJT. Analyzed the data: JS RB LJL PEC RJT. Contributed reagents/materials/analysis tools: LAD JDE WRG VMH. Wrote the paper: JS RB KDD JMN VMH WHR.
Descrição: Rheumatoid arthritis (RA) is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.
Editor: United States: Public Library of Science
Idioma: Inglês

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Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis

Sokolove, Jeremy ; Bromberg, Reuven ; Deane, Kevin D ; Lahey, Lauren J ; Derber, Lezlie A ; Chandra, Piyanka E ; Edison, Jess D ; Gilliland, William R ; Tibshirani, Robert J ; Norris, Jill M ; Holers, V Michael ; Robinson, William H Matloubian, Mehrdad

United States: Public Library of Science

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