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Intravenous immunoglobulin preparation increases myoplasmic calcium concentration by activating the

B G van Engelen1, A A Benders, R A Wevers

  • 1Department of Neurology, University Hospital Nijmegen, The Netherlands. b.vanengelen@czzoneu.azn.nl

Journal of the Neurological Sciences
|April 29, 1998
PubMed

Insights

Human intravenous immunoglobulin (IVIg) preparations can release calcium from muscle cells by affecting the dihydropyridine receptor. This effect, mediated by an unknown serum protein, is crucial for understanding IVIg side effects in neuromuscular diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Intravenous immunoglobulin (IVIg) is a therapy used for various autoimmune and neuromuscular diseases.
  • The precise mechanisms underlying IVIg's therapeutic effects and potential side effects are not fully understood.
  • Calcium (Ca2+) signaling plays a critical role in muscle cell function.

Purpose of the Study:

  • To investigate the effect of IVIg on calcium release in human skeletal muscle cells.
  • To identify the specific cellular pathways involved in the IVIg-mediated calcium response.
  • To determine if the active component in IVIg is IgG or another serum protein.

Main Methods:

  • Cultured human skeletal muscle cells were treated with IVIg.
  • Calcium release was measured in a dose-dependent manner.
  • Specific receptor blockers (dihydropyridine-ryanodine, voltage-operated Na+-channels, acetylcholine receptors) were used to elucidate the mechanism.

Main Results:

  • IVIg induced a dose-dependent release of Ca2+ from the sarcoplasmic reticulum in muscle cells.
  • The calcium response was abrogated by blocking the dihydropyridine-ryanodine receptor complex.
  • The effect was not mediated by IgG, varied between manufacturers, and was abolished by heating, suggesting an unidentified protein component.

Conclusions:

  • An unidentified serum protein in IVIg influences human muscle cells via the dihydropyridine receptor.
  • This interaction affects calcium release and may explain certain IVIg-related side effects in neuromuscular conditions.
  • Further research is needed to identify the specific protein and its role in IVIg therapy.

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