Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

Matthew D. Linnik, Jay Z. Hu, Kenneth R. Heilbrunn, Vibeke Strand, Frank L. Hurley, Tenshang Joh, D. Alarcón-Segovia, G. Appel, C. Aranow, S. Ballou, M. A. Becker, N. Becker, M. H. Belmont, A. Bohan, E. P. Boling, S. Bombardieri, W. G. Brelsford, J. P. Buyon, M. H. Cardiel, N. L. CarteronJ. J. Condemi, M. E. Cronin, J. J. Cush, R. DeHoratius, D. Desir, M. Edwards, M. A. El-Shahawy, P. Emery, L. R. Espinoza, T. H. Finkel, M. Fondal, P. Fortin, R. A. Furie, M. C. Genovese, T. Geppert, A. Gil-Aguado, G. S. Gilkeson, E. Ginzler, O. S. Gluck, J. L. Granda, J. Grossman, F. Hiepe, M. Hill, P. Howard, C. Hura, M. Ingelmo, A. Jaffer, J. Jakes, J. P. Kalden, K. C. Kalunian, G. M. Kammer, K. Kanick, J. Kaplan, S. Kaplan, R. Katz, H. M. Kenney, M. Khamashta, A. J. Kivitz, M. Krishnan, N. A. Kurtzman, M. Liebling, J. S. Lindberg, S. H. Lourie, J. Loveless, S. Manzi, K. Martin, J. McKay, J. Merrill, L. W. Moreland, M. C. Neuwelt, M. Petri, B. C. Poque, R. J. Quinet, R. Ramsey-Goldman, S. G. Rosenblatt, N. Rothfield, N. Scarpa, M. Schneider, J. T. Schousboe, L. K. Sewell, W. J. Shergy, Y. Sherrer, J. Sibilia, D. Smith, B. Spinowitz, M. Spira, R. Staud, S. Stern, M. P. Stevens, G. Sturfelt, W. Surbeck, E. A. Tindall, A. Torres, J. Tumlin, R. Van Vollenhoven, J. Varga, A. Vijayan, M. Vilardell-Tarres, D. Wallace, C. Weaver, M. Zummer

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

Original languageEnglish (US)
Pages (from-to)1129-1137
Number of pages9
JournalArthritis and rheumatism
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

Systemic Lupus Erythematosus
Disease Progression
Anti-Idiotypic Antibodies
Kidney
Antibodies
DNA
Lupus Nephritis
Radioimmunoprecipitation Assay
Confidence Intervals
Proportional Hazards Models
Randomized Controlled Trials
Placebos
Incidence
Therapeutics
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. / Linnik, Matthew D.; Hu, Jay Z.; Heilbrunn, Kenneth R.; Strand, Vibeke; Hurley, Frank L.; Joh, Tenshang; Alarcón-Segovia, D.; Appel, G.; Aranow, C.; Ballou, S.; Becker, M. A.; Becker, N.; Belmont, M. H.; Bohan, A.; Boling, E. P.; Bombardieri, S.; Brelsford, W. G.; Buyon, J. P.; Cardiel, M. H.; Carteron, N. L.; Condemi, J. J.; Cronin, M. E.; Cush, J. J.; DeHoratius, R.; Desir, D.; Edwards, M.; El-Shahawy, M. A.; Emery, P.; Espinoza, L. R.; Finkel, T. H.; Fondal, M.; Fortin, P.; Furie, R. A.; Genovese, M. C.; Geppert, T.; Gil-Aguado, A.; Gilkeson, G. S.; Ginzler, E.; Gluck, O. S.; Granda, J. L.; Grossman, J.; Hiepe, F.; Hill, M.; Howard, P.; Hura, C.; Ingelmo, M.; Jaffer, A.; Jakes, J.; Kalden, J. P.; Kalunian, K. C.; Kammer, G. M.; Kanick, K.; Kaplan, J.; Kaplan, S.; Katz, R.; Kenney, H. M.; Khamashta, M.; Kivitz, A. J.; Krishnan, M.; Kurtzman, N. A.; Liebling, M.; Lindberg, J. S.; Lourie, S. H.; Loveless, J.; Manzi, S.; Martin, K.; McKay, J.; Merrill, J.; Moreland, L. W.; Neuwelt, M. C.; Petri, M.; Poque, B. C.; Quinet, R. J.; Ramsey-Goldman, R.; Rosenblatt, S. G.; Rothfield, N.; Scarpa, N.; Schneider, M.; Schousboe, J. T.; Sewell, L. K.; Shergy, W. J.; Sherrer, Y.; Sibilia, J.; Smith, D.; Spinowitz, B.; Spira, M.; Staud, R.; Stern, S.; Stevens, M. P.; Sturfelt, G.; Surbeck, W.; Tindall, E. A.; Torres, A.; Tumlin, J.; Van Vollenhoven, R.; Varga, J.; Vijayan, A.; Vilardell-Tarres, M.; Wallace, D.; Weaver, C.; Zummer, M.

In: Arthritis and rheumatism, Vol. 52, No. 4, 01.04.2005, p. 1129-1137.

Research output: Contribution to journalArticle

Linnik, MD, Hu, JZ, Heilbrunn, KR, Strand, V, Hurley, FL, Joh, T, Alarcón-Segovia, D, Appel, G, Aranow, C, Ballou, S, Becker, MA, Becker, N, Belmont, MH, Bohan, A, Boling, EP, Bombardieri, S, Brelsford, WG, Buyon, JP, Cardiel, MH, Carteron, NL, Condemi, JJ, Cronin, ME, Cush, JJ, DeHoratius, R, Desir, D, Edwards, M, El-Shahawy, MA, Emery, P, Espinoza, LR, Finkel, TH, Fondal, M, Fortin, P, Furie, RA, Genovese, MC, Geppert, T, Gil-Aguado, A, Gilkeson, GS, Ginzler, E, Gluck, OS, Granda, JL, Grossman, J, Hiepe, F, Hill, M, Howard, P, Hura, C, Ingelmo, M, Jaffer, A, Jakes, J, Kalden, JP, Kalunian, KC, Kammer, GM, Kanick, K, Kaplan, J, Kaplan, S, Katz, R, Kenney, HM, Khamashta, M, Kivitz, AJ, Krishnan, M, Kurtzman, NA, Liebling, M, Lindberg, JS, Lourie, SH, Loveless, J, Manzi, S, Martin, K, McKay, J, Merrill, J, Moreland, LW, Neuwelt, MC, Petri, M, Poque, BC, Quinet, RJ, Ramsey-Goldman, R, Rosenblatt, SG, Rothfield, N, Scarpa, N, Schneider, M, Schousboe, JT, Sewell, LK, Shergy, WJ, Sherrer, Y, Sibilia, J, Smith, D, Spinowitz, B, Spira, M, Staud, R, Stern, S, Stevens, MP, Sturfelt, G, Surbeck, W, Tindall, EA, Torres, A, Tumlin, J, Van Vollenhoven, R, Varga, J, Vijayan, A, Vilardell-Tarres, M, Wallace, D, Weaver, C & Zummer, M 2005, 'Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus', Arthritis and rheumatism, vol. 52, no. 4, pp. 1129-1137. https://doi.org/10.1002/art.20980
Linnik, Matthew D. ; Hu, Jay Z. ; Heilbrunn, Kenneth R. ; Strand, Vibeke ; Hurley, Frank L. ; Joh, Tenshang ; Alarcón-Segovia, D. ; Appel, G. ; Aranow, C. ; Ballou, S. ; Becker, M. A. ; Becker, N. ; Belmont, M. H. ; Bohan, A. ; Boling, E. P. ; Bombardieri, S. ; Brelsford, W. G. ; Buyon, J. P. ; Cardiel, M. H. ; Carteron, N. L. ; Condemi, J. J. ; Cronin, M. E. ; Cush, J. J. ; DeHoratius, R. ; Desir, D. ; Edwards, M. ; El-Shahawy, M. A. ; Emery, P. ; Espinoza, L. R. ; Finkel, T. H. ; Fondal, M. ; Fortin, P. ; Furie, R. A. ; Genovese, M. C. ; Geppert, T. ; Gil-Aguado, A. ; Gilkeson, G. S. ; Ginzler, E. ; Gluck, O. S. ; Granda, J. L. ; Grossman, J. ; Hiepe, F. ; Hill, M. ; Howard, P. ; Hura, C. ; Ingelmo, M. ; Jaffer, A. ; Jakes, J. ; Kalden, J. P. ; Kalunian, K. C. ; Kammer, G. M. ; Kanick, K. ; Kaplan, J. ; Kaplan, S. ; Katz, R. ; Kenney, H. M. ; Khamashta, M. ; Kivitz, A. J. ; Krishnan, M. ; Kurtzman, N. A. ; Liebling, M. ; Lindberg, J. S. ; Lourie, S. H. ; Loveless, J. ; Manzi, S. ; Martin, K. ; McKay, J. ; Merrill, J. ; Moreland, L. W. ; Neuwelt, M. C. ; Petri, M. ; Poque, B. C. ; Quinet, R. J. ; Ramsey-Goldman, R. ; Rosenblatt, S. G. ; Rothfield, N. ; Scarpa, N. ; Schneider, M. ; Schousboe, J. T. ; Sewell, L. K. ; Shergy, W. J. ; Sherrer, Y. ; Sibilia, J. ; Smith, D. ; Spinowitz, B. ; Spira, M. ; Staud, R. ; Stern, S. ; Stevens, M. P. ; Sturfelt, G. ; Surbeck, W. ; Tindall, E. A. ; Torres, A. ; Tumlin, J. ; Van Vollenhoven, R. ; Varga, J. ; Vijayan, A. ; Vilardell-Tarres, M. ; Wallace, D. ; Weaver, C. ; Zummer, M. / Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. In: Arthritis and rheumatism. 2005 ; Vol. 52, No. 4. pp. 1129-1137.
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abstract = "Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50{\%} reduction in anti-dsDNA antibody levels is associated with a 52{\%} reduction (95{\%} confidence interval [95{\%} CI] 26-68{\%}, nominal P = 0.0007) and a 53{\%} reduction (95{\%} CI 33-69{\%}, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0{\%} and 4.1{\%}, respectively) than in patients with stable or increasing antibody levels (21.3{\%} and 20.3{\%}, respectively). Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.",
author = "Linnik, {Matthew D.} and Hu, {Jay Z.} and Heilbrunn, {Kenneth R.} and Vibeke Strand and Hurley, {Frank L.} and Tenshang Joh and D. Alarc{\'o}n-Segovia and G. Appel and C. Aranow and S. Ballou and Becker, {M. A.} and N. Becker and Belmont, {M. H.} and A. Bohan and Boling, {E. P.} and S. Bombardieri and Brelsford, {W. G.} and Buyon, {J. P.} and Cardiel, {M. H.} and Carteron, {N. L.} and Condemi, {J. J.} and Cronin, {M. E.} and Cush, {J. J.} and R. DeHoratius and D. Desir and M. Edwards and El-Shahawy, {M. A.} and P. Emery and Espinoza, {L. R.} and Finkel, {T. H.} and M. Fondal and P. Fortin and Furie, {R. A.} and Genovese, {M. C.} and T. Geppert and A. Gil-Aguado and Gilkeson, {G. S.} and E. Ginzler and Gluck, {O. S.} and Granda, {J. L.} and J. Grossman and F. Hiepe and M. Hill and P. Howard and C. Hura and M. Ingelmo and A. Jaffer and J. Jakes and Kalden, {J. P.} and Kalunian, {K. C.} and Kammer, {G. M.} and K. Kanick and J. Kaplan and S. Kaplan and R. Katz and Kenney, {H. M.} and M. Khamashta and Kivitz, {A. J.} and M. Krishnan and Kurtzman, {N. A.} and M. Liebling and Lindberg, {J. S.} and Lourie, {S. H.} and J. Loveless and S. Manzi and K. Martin and J. McKay and J. Merrill and Moreland, {L. W.} and Neuwelt, {M. C.} and M. Petri and Poque, {B. C.} and Quinet, {R. J.} and R. Ramsey-Goldman and Rosenblatt, {S. G.} and N. Rothfield and N. Scarpa and M. Schneider and Schousboe, {J. T.} and Sewell, {L. K.} and Shergy, {W. J.} and Y. Sherrer and J. Sibilia and D. Smith and B. Spinowitz and M. Spira and R. Staud and S. Stern and Stevens, {M. P.} and G. Sturfelt and W. Surbeck and Tindall, {E. A.} and A. Torres and J. Tumlin and {Van Vollenhoven}, R. and J. Varga and A. Vijayan and M. Vilardell-Tarres and D. Wallace and C. Weaver and M. Zummer",
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TY - JOUR

T1 - Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

AU - Linnik, Matthew D.

AU - Hu, Jay Z.

AU - Heilbrunn, Kenneth R.

AU - Strand, Vibeke

AU - Hurley, Frank L.

AU - Joh, Tenshang

AU - Alarcón-Segovia, D.

AU - Appel, G.

AU - Aranow, C.

AU - Ballou, S.

AU - Becker, M. A.

AU - Becker, N.

AU - Belmont, M. H.

AU - Bohan, A.

AU - Boling, E. P.

AU - Bombardieri, S.

AU - Brelsford, W. G.

AU - Buyon, J. P.

AU - Cardiel, M. H.

AU - Carteron, N. L.

AU - Condemi, J. J.

AU - Cronin, M. E.

AU - Cush, J. J.

AU - DeHoratius, R.

AU - Desir, D.

AU - Edwards, M.

AU - El-Shahawy, M. A.

AU - Emery, P.

AU - Espinoza, L. R.

AU - Finkel, T. H.

AU - Fondal, M.

AU - Fortin, P.

AU - Furie, R. A.

AU - Genovese, M. C.

AU - Geppert, T.

AU - Gil-Aguado, A.

AU - Gilkeson, G. S.

AU - Ginzler, E.

AU - Gluck, O. S.

AU - Granda, J. L.

AU - Grossman, J.

AU - Hiepe, F.

AU - Hill, M.

AU - Howard, P.

AU - Hura, C.

AU - Ingelmo, M.

AU - Jaffer, A.

AU - Jakes, J.

AU - Kalden, J. P.

AU - Kalunian, K. C.

AU - Kammer, G. M.

AU - Kanick, K.

AU - Kaplan, J.

AU - Kaplan, S.

AU - Katz, R.

AU - Kenney, H. M.

AU - Khamashta, M.

AU - Kivitz, A. J.

AU - Krishnan, M.

AU - Kurtzman, N. A.

AU - Liebling, M.

AU - Lindberg, J. S.

AU - Lourie, S. H.

AU - Loveless, J.

AU - Manzi, S.

AU - Martin, K.

AU - McKay, J.

AU - Merrill, J.

AU - Moreland, L. W.

AU - Neuwelt, M. C.

AU - Petri, M.

AU - Poque, B. C.

AU - Quinet, R. J.

AU - Ramsey-Goldman, R.

AU - Rosenblatt, S. G.

AU - Rothfield, N.

AU - Scarpa, N.

AU - Schneider, M.

AU - Schousboe, J. T.

AU - Sewell, L. K.

AU - Shergy, W. J.

AU - Sherrer, Y.

AU - Sibilia, J.

AU - Smith, D.

AU - Spinowitz, B.

AU - Spira, M.

AU - Staud, R.

AU - Stern, S.

AU - Stevens, M. P.

AU - Sturfelt, G.

AU - Surbeck, W.

AU - Tindall, E. A.

AU - Torres, A.

AU - Tumlin, J.

AU - Van Vollenhoven, R.

AU - Varga, J.

AU - Vijayan, A.

AU - Vilardell-Tarres, M.

AU - Wallace, D.

AU - Weaver, C.

AU - Zummer, M.

PY - 2005/4/1

Y1 - 2005/4/1

N2 - Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

AB - Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

UR - http://www.scopus.com/inward/record.url?scp=20244383590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244383590&partnerID=8YFLogxK

U2 - 10.1002/art.20980

DO - 10.1002/art.20980

M3 - Article

C2 - 15818711

AN - SCOPUS:20244383590

VL - 52

SP - 1129

EP - 1137

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 4

ER -