Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis

Yves Renaudineau, Sabine Croquefer, Sandrine Jousse, Eric Renaudineau, Valérie Devauchelle, Paul Guéguen, Catherine Hanrotel, Boris Gilburd, Alain Saraux, Yehuda Shoenfeld, Chaim Putterman, Pierre Youinou

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Objective. Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with aalpha;-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. Methods. One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-α-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. Results. Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-α-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-α-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-α-actinin antibodies (P < 0.01). In patients with GN, anti-α-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with α-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. Conclusion. The α-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

Original languageEnglish (US)
Pages (from-to)2523-2532
Number of pages10
JournalArthritis and Rheumatism
Volume54
Issue number8
DOIs
StatePublished - Aug 2006

Fingerprint

Actinin
Lupus Nephritis
Anti-Idiotypic Antibodies
Systemic Lupus Erythematosus
Glomerulonephritis
Antibodies
DNA
Serum
Enzyme-Linked Immunosorbent Assay
Immunoenzyme Techniques
Autoantibodies
Antibody Affinity
Mesangial Cells
Indirect Fluorescent Antibody Technique
Rheumatic Diseases
Blood Donors
Multicenter Studies
Western Blotting

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Renaudineau, Y., Croquefer, S., Jousse, S., Renaudineau, E., Devauchelle, V., Guéguen, P., ... Youinou, P. (2006). Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis. Arthritis and Rheumatism, 54(8), 2523-2532. https://doi.org/10.1002/art.22015

Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis. / Renaudineau, Yves; Croquefer, Sabine; Jousse, Sandrine; Renaudineau, Eric; Devauchelle, Valérie; Guéguen, Paul; Hanrotel, Catherine; Gilburd, Boris; Saraux, Alain; Shoenfeld, Yehuda; Putterman, Chaim; Youinou, Pierre.

In: Arthritis and Rheumatism, Vol. 54, No. 8, 08.2006, p. 2523-2532.

Research output: Contribution to journalArticle

Renaudineau, Y, Croquefer, S, Jousse, S, Renaudineau, E, Devauchelle, V, Guéguen, P, Hanrotel, C, Gilburd, B, Saraux, A, Shoenfeld, Y, Putterman, C & Youinou, P 2006, 'Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis', Arthritis and Rheumatism, vol. 54, no. 8, pp. 2523-2532. https://doi.org/10.1002/art.22015
Renaudineau Y, Croquefer S, Jousse S, Renaudineau E, Devauchelle V, Guéguen P et al. Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis. Arthritis and Rheumatism. 2006 Aug;54(8):2523-2532. https://doi.org/10.1002/art.22015
Renaudineau, Yves ; Croquefer, Sabine ; Jousse, Sandrine ; Renaudineau, Eric ; Devauchelle, Valérie ; Guéguen, Paul ; Hanrotel, Catherine ; Gilburd, Boris ; Saraux, Alain ; Shoenfeld, Yehuda ; Putterman, Chaim ; Youinou, Pierre. / Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 8. pp. 2523-2532.
@article{150c409848e24a6b99649ac53aa7af7e,
title = "Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis",
abstract = "Objective. Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with aalpha;-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. Methods. One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-α-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. Results. Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-α-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-α-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-α-actinin antibodies (P < 0.01). In patients with GN, anti-α-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with α-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. Conclusion. The α-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.",
author = "Yves Renaudineau and Sabine Croquefer and Sandrine Jousse and Eric Renaudineau and Val{\'e}rie Devauchelle and Paul Gu{\'e}guen and Catherine Hanrotel and Boris Gilburd and Alain Saraux and Yehuda Shoenfeld and Chaim Putterman and Pierre Youinou",
year = "2006",
month = "8",
doi = "10.1002/art.22015",
language = "English (US)",
volume = "54",
pages = "2523--2532",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

TY - JOUR

T1 - Association of α-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis

AU - Renaudineau, Yves

AU - Croquefer, Sabine

AU - Jousse, Sandrine

AU - Renaudineau, Eric

AU - Devauchelle, Valérie

AU - Guéguen, Paul

AU - Hanrotel, Catherine

AU - Gilburd, Boris

AU - Saraux, Alain

AU - Shoenfeld, Yehuda

AU - Putterman, Chaim

AU - Youinou, Pierre

PY - 2006/8

Y1 - 2006/8

N2 - Objective. Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with aalpha;-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. Methods. One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-α-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. Results. Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-α-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-α-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-α-actinin antibodies (P < 0.01). In patients with GN, anti-α-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with α-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. Conclusion. The α-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

AB - Objective. Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with aalpha;-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. Methods. One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-α-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. Results. Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-α-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-α-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-α-actinin antibodies (P < 0.01). In patients with GN, anti-α-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with α-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. Conclusion. The α-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

UR - http://www.scopus.com/inward/record.url?scp=33746990232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746990232&partnerID=8YFLogxK

U2 - 10.1002/art.22015

DO - 10.1002/art.22015

M3 - Article

C2 - 16868973

AN - SCOPUS:33746990232

VL - 54

SP - 2523

EP - 2532

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 8

ER -