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IVIg selectively and rapidly decreases circulating pathogenic autoantibodies in pemphigus vulgaris.
Autoimmunity. 2006 Nov;39(7):601-7.
Bystryn JC, Jiao D.
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.
Background:
Intraveneous immunoglobulin (IVIg) is increasingly used to treat
pemphigus vulgaris (PV). The mechanism by which it does so is not
known. The following study was conducted to confirm the effectiveness
of IVIg for the acute control of active PV and to elucidate the
mechanism by which it does.
Methods: Twelve patients with active and
severe PV unresponsive to conventional therapy with high doses of
systemic steroids together with or without a cytotoxic drug were
treated with a single dose of IVIg (400 mg/kg/day for 5 days). All
patients were concurrently given cyclophosphamide or azathioprine of
not already on one of these two drugs. The primary end-points were
healing of skin lesions, changes in serum levels of intercelular (IC)
autoantibodies and in steroid doses one to 3 weeks after initiation of
IVIg.Results: Within 1 week of initiating IVIg the activity of PV was
controlled in most cases. Within 3 weeks the average baseline dose of
systemic steroid was reduced by 40%. Serum levels of IC antibodies
rapidly declined by an average of 59% within 1 week of initiating IVIg
and by 70% within 2 weeks. The decrease was selective, as the average
serum levels of antibody to varicella-herpes zoster did not decrease in
the 4 patients in whom they were measured. The decrease in IC
antibodies was inversely related to serum levels of total
inmmunoglobulin (IgG). The decrease in IC antibodies was not due to
blocking factors in the IVIg preparation and was too rapid to be due to
suppression of IgG synthesis, suggesting that it resulted from
increased catabolism.Conclusions: IVIg can rapidly control active PV
unresponsive to conventional therapy by causing a selective and very
rapid decline in the autoantibodies that mediate the disease. We
believe it does so by increasing the catabolism of all serum IgG
antibodies, and that this results in a selective decrease in only
abnormal autoantibodies as catabolized normal anti bodies are replaced
by those present in the IVIg preparation. IVIg is the first treatment
that achieves the ideal therapeutic goal in auto-antibody diseases, the
selective removal of the pathogenic antibodies without affecting the
level of normal antibodies.
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