Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin

I. Krause, M. Blank, J. Kopolovic, A. Afek, I. Goldberg, Yaron Tomer, Y. Shoenfeld

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Objective. To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods. BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. Results. Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDNA and aCL antibodies in the IVGG preparation. Conclusion. Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of the pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

Original languageEnglish (US)
Pages (from-to)1068-1074
Number of pages7
JournalJournal of Rheumatology
Volume22
Issue number6
StatePublished - 1995
Externally publishedYes

Fingerprint

Antiphospholipid Syndrome
gamma-Globulins
Systemic Lupus Erythematosus
Fetal Resorption
Autoantibodies
Immunoglobulin Fc Fragments
Blood Sedimentation
Leukocyte Count
Immunoglobulins
Monoclonal Antibodies
Kidney
Partial Thromboplastin Time
Antinuclear Antibodies
Intravenous Immunoglobulins
Therapeutics
Platelet Count
Proteinuria
Immunization
Enzyme-Linked Immunosorbent Assay
DNA

Keywords

  • experimental antiphospholipid syndrome
  • experimental systemic lupus erythematosus
  • intravenous gamma globulin

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Krause, I., Blank, M., Kopolovic, J., Afek, A., Goldberg, I., Tomer, Y., & Shoenfeld, Y. (1995). Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin. Journal of Rheumatology, 22(6), 1068-1074.

Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin. / Krause, I.; Blank, M.; Kopolovic, J.; Afek, A.; Goldberg, I.; Tomer, Yaron; Shoenfeld, Y.

In: Journal of Rheumatology, Vol. 22, No. 6, 1995, p. 1068-1074.

Research output: Contribution to journalArticle

Krause, I, Blank, M, Kopolovic, J, Afek, A, Goldberg, I, Tomer, Y & Shoenfeld, Y 1995, 'Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin', Journal of Rheumatology, vol. 22, no. 6, pp. 1068-1074.
Krause, I. ; Blank, M. ; Kopolovic, J. ; Afek, A. ; Goldberg, I. ; Tomer, Yaron ; Shoenfeld, Y. / Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin. In: Journal of Rheumatology. 1995 ; Vol. 22, No. 6. pp. 1068-1074.
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abstract = "Objective. To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods. BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. Results. Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDNA and aCL antibodies in the IVGG preparation. Conclusion. Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of the pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.",
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AU - Goldberg, I.

AU - Tomer, Yaron

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AB - Objective. To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods. BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. Results. Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDNA and aCL antibodies in the IVGG preparation. Conclusion. Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of the pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

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