Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes

Q. Z. Li, J. Zhou, A. E. Wandstrat, F. Carr-Johnson, V. Branch, D. R. Karp, C. Mohan, E. K. Wakeland, N. J. Olsen

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

Original languageEnglish (US)
Pages (from-to)60-70
Number of pages11
JournalClinical and Experimental Immunology
Volume147
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Protein Array Analysis
Systemic Lupus Erythematosus
Autoantibodies
Immunoglobulin G
Immunoglobulin M
Autoantigens
Kidney
DNA
Proteome
Microarray Analysis
Serum
Histones
Cluster Analysis
Longitudinal Studies
Collagen
RNA
Antigens

Keywords

  • Autoantibodies
  • Autoantigens
  • Autoimmunity
  • Incomplete lupus
  • Proteome microarray
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology

Cite this

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes. / Li, Q. Z.; Zhou, J.; Wandstrat, A. E.; Carr-Johnson, F.; Branch, V.; Karp, D. R.; Mohan, C.; Wakeland, E. K.; Olsen, N. J.

In: Clinical and Experimental Immunology, Vol. 147, No. 1, 01.2007, p. 60-70.

Research output: Contribution to journalArticle

Li, Q. Z. ; Zhou, J. ; Wandstrat, A. E. ; Carr-Johnson, F. ; Branch, V. ; Karp, D. R. ; Mohan, C. ; Wakeland, E. K. ; Olsen, N. J. / Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes. In: Clinical and Experimental Immunology. 2007 ; Vol. 147, No. 1. pp. 60-70.
@article{41d69c1910dd4ff390e97a9141e88543,
title = "Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes",
abstract = "The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26{\%} of SLE and 19{\%} of ILE samples; elevated IgM autoantibodies were present in 13{\%} of SLE and 17{\%} of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.",
keywords = "Autoantibodies, Autoantigens, Autoimmunity, Incomplete lupus, Proteome microarray, Systemic lupus erythematosus",
author = "Li, {Q. Z.} and J. Zhou and Wandstrat, {A. E.} and F. Carr-Johnson and V. Branch and Karp, {D. R.} and C. Mohan and Wakeland, {E. K.} and Olsen, {N. J.}",
year = "2007",
month = "1",
doi = "10.1111/j.1365-2249.2006.03251.x",
language = "English (US)",
volume = "147",
pages = "60--70",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes

AU - Li, Q. Z.

AU - Zhou, J.

AU - Wandstrat, A. E.

AU - Carr-Johnson, F.

AU - Branch, V.

AU - Karp, D. R.

AU - Mohan, C.

AU - Wakeland, E. K.

AU - Olsen, N. J.

PY - 2007/1

Y1 - 2007/1

N2 - The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

AB - The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

KW - Autoantibodies

KW - Autoantigens

KW - Autoimmunity

KW - Incomplete lupus

KW - Proteome microarray

KW - Systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=33845485330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845485330&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2249.2006.03251.x

DO - 10.1111/j.1365-2249.2006.03251.x

M3 - Article

VL - 147

SP - 60

EP - 70

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 1

ER -