IgG introduction
Introduction
Immunoglobulins are
proteins produced by cells of the B lymphocyte lineage
that are the major effector molecules of the humoral
immune system. Immunoglobulin molecules are antibodies
that react with specific antigens, although in many
circumstances, the specificity of a given immunoglobulin
antibody is unknown. Immunoglobulin preparations from
human blood were first used in clinical medicine in 1952
to treat immune deficiency conditions. At that time, the
only available preparations required intramuscular
administration. In the past decade, several
immunoglobulin preparations for intravenous
administration have become available. Although initially
used for immune deficiency states, intravenous
immunoglobulin (IVIG) has also been utilized as a
prophylactic and therapeutic reagent in a variety of
other conditions. The use of IVIG has undergone
tremendous growth in the past several years. This rapid
growth in use is the result of improvements in the
preparations of IVIG, which have led to reduced
morbidity and reports of its benefits in a number of
unexpected circumstances. IVIG has been used in such
diverse diseases as primary immunodeficiencies,
pediatric AIDS, infections in low birth weight infants,
bone marrow transplantation, chronic lymphocytic
leukemia, idiopathic thrombocytopenic purpura, Kawasaki
syndrome, and demyelinating polyneuropathies. However,
important questions regarding its use still remain. To
assess the usefulness of IVIG in diseases where
substantive data existed, the National Institute of
Allergy and Infectious Diseases and the Office of
Medical Applications of Research of the National
Institutes of Health convened a Consensus Development
Conference on Intravenous Immunoglobulin: Prevention and
Treatment of Disease on May 21-23, 1990. Cosponsors were
the National Cancer Institute, National Heart, Lung, and
Blood Institute, National Institute of Child Health and
Human Development, National Institute of Neurological
Disorders and Stroke, and the Food and Drug
Administration.
In the various disease
states in which IVIG has been used, the following
questions were considered:
- What are the data to
support the efficacy of IVIG in these circumstances?
- What are the
appropriate dosage and treatment schedules?
- Are all IVIG
preparations equally efficacious?
- What are the risks
involved in the use of IVIG?
- What are the
mechanisms of action?
- What are the
directions for future research?
After a day and a half of
presentations by experts in the field and discussion by
the audience, a consensus panel drawn from specialists
and generalists from the medical profession and related
scientific disciplines, clinical investigators, and
public representatives considered the evidence and came
to the conclusions on the following pages.
What Are the Data To
Support the Efficacy of IVIG in These Circumstances?
Primary
Immunodeficiencies
The beneficial effects of
intramuscular (IM) injection of immune globulin (IG) in
the prophylactic treatment of patients with primary
immunodeficiency syndromes have been well established.
Early studies based on small sample sizes have indicated
that almost any desired blood level of IgG can be
obtained by use of intravenous immunoglobulin and that
infection rates are reduced by use of IVIG as compared
with IM IG. IVIG has been shown to ameliorate chronic
sinopulmonary disease that developed in patients on
long-term IM IG. There is a suggestion that chronic
enterovirus meningoencephalitis in patients with
X-linked agammaglobulinemia may be less frequent in
those receiving prophylactic IVIG as compared with
historical data in which IM IG was used. Hence, IVIG has
become the current standard in clinical practice for
replacement therapy of patients with primary
immunodeficiencies (e.g., X-linked agammaglobulinemia
and common variable immunodeficiency and immunoglobulin
subclass deficiency in which deficiencies of antibody
production to common pathogens can be demonstrated).
Studies have shown that maintenance of a trough level of
500 mg/dL is beneficial. Dose ranges of 200-800 mg/kg/mo
have been shown to be effective, but dose or frequency
of infusions must be tailored to the individual patient,
because half life of infused IVIG varies widely.
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