Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays

Li Zhen Quan, Chun Xie, Tianfu Wu, Meggan Mackay, Cynthia Aranow, Chaim Putterman, Chandra Mohan

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Nephrophilic autoantibodies dominate the seroprofile in lupus, but their fine specificities remain ill defined. We constructed a multiplexed proteome microarray bearing about 30 antigens known to be expressed in the glomerular milieu and used it to study serum autoantibodies in lupus. Compared with normal serum, serum from B6.Sle1.lpr lupus mice (C57BL/6 mice homozygous for the NZM2410/NZW allele of Sle1 as well as the FASlpr defect) exhibited high levels of IgG and IgM antiglomerular as well as anti-double-stranded DNA/chromatin Abs and variable levels of Abs to α-actinin, aggrecan, collagen, entactin, fibrinogen, hemocyanin, heparan sulphate, laminin, myosin, proteoglycans, and histones. The use of these glomerular proteome arrays also revealed 5 distinct clusters of IgG autoreactivity in the sera of lupus patients. Whereas 2 of these IgG reactivity clusters (DNA/chromatin/glomeruli and laminin/myosin/Matrigel/vimentin/heparan sulphate) showed association with disease activity, the other 3 reactivity clusters (histones, vitronectin/collagen/chondroitin sulphate, and entactin/fibrinogen/hyaluronic acid) did not. Human lupus sera also displayed 2 distinct IgM autoantibody clusters, one reactive to DNA and the other apparently polyreactive. Interestingly, the presence of IgM polyreactivity in patient sera was associated with reduced disease severity. Hence, the glomerular proteome array promises to be a powerful analytical tool for uncovering novel autoantibody disease associations and for distinguishing patients at high risk for end-organ disease.

Original languageEnglish (US)
Pages (from-to)3428-3439
Number of pages12
JournalJournal of Clinical Investigation
Volume115
Issue number12
DOIs
StatePublished - Dec 2005

Fingerprint

Proteome
Autoantibodies
Serum
Immunoglobulin M
Heparitin Sulfate
Immunoglobulin G
Laminin
Myosins
Histones
Fibrinogen
Chromatin
DNA
Collagen
Actinin
Vitronectin
Aggrecans
Hemocyanin
Chondroitin Sulfates
Vimentin
Proteoglycans

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays. / Quan, Li Zhen; Xie, Chun; Wu, Tianfu; Mackay, Meggan; Aranow, Cynthia; Putterman, Chaim; Mohan, Chandra.

In: Journal of Clinical Investigation, Vol. 115, No. 12, 12.2005, p. 3428-3439.

Research output: Contribution to journalArticle

Quan, Li Zhen ; Xie, Chun ; Wu, Tianfu ; Mackay, Meggan ; Aranow, Cynthia ; Putterman, Chaim ; Mohan, Chandra. / Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 12. pp. 3428-3439.
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