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Update on the treatment of primary immunodeficiencies.
Allergol Immunopathol (Madr). 2007 Sep;35(5):184-192.
García JM, Español T, Gurbindo MD, Casas C C.
Allergy
and Immunology Unit. Department of Paediatrics. Cruces Hospital.
Barakaldo. Basque Country. Spain.
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.
A general review of
advances in the treatment of Primary Immunodeficiencies (PID) has been
performed. Treatment with immunoglobulins is indicated in cases of
humoral immunodeficiencies and in selected cases of combined
immunodeficiencies.
The use of intramuscular immunoglobulins in the
treatment of PID was abandoned after obtaining the intravenous
immunoglobulins, since these are much more effective and have fewer
adverse effects. Now subcutaneous immunoglobulins are also available.
Immunoglobulins help to keep the patients free of symptoms and
infections as these substances are able to neutralise infectious
agents, modulate and promote the immune response and favour
phagocytosis. Adverse effects have been reported in 5-15 % of patients
receiving IVIg, and patients with deficiencies of subclasses of IgG
with IgA deficiency and/or anti-IgA antibodies are at risk of severe
reactions. No severe adverse effects of subcutaneous immuneglobulins
have been reported and the medication can be self-administered. The
efficacy and safety of IVIg and SCIg are similar and SCIg administered
at home is associated with better quality of life. Stem Cell
Transplantation (SCT) in Primary Immunodeficiencies is aimed at
restoring the number and/or function of lymphocytes or phagocytes.
Matched, related or unrelated donors, or related haploidentical donors
are selected. HLA class II mismatched unrelated donors are avoided
owing to the risk of severe graft versus host disease (GVHD). Stem
cells are obtained from bone marrow, cord blood or peripheral blood.
Prophylactic immunossupression (as well as donor T lymphocyte depletion
in haploidentical and unrelated donors) is performed to avoid or
minimize GVHD. Less toxic "reduced intensity" protocols now exist for
pre-transplantation conditioning, indicated to avoid graft rejection if
there is residual T-lymphocyte immunity in the host. In the majority of
Severe Combined Immunodeficiencies (SCID), SCT results in T lymphocytes
graft and the antibody immunodeficiency persists in many cases. The
results are better the earlier it is performed, with the absence of
previous infections, and with the degree of matching. The patient must
be maintained in a laminar flow room with broad anti-infectious
prophylaxis and with the intravenous administration of gammaglobulin
for a variable period. Many other complications can be expected. Gene
therapy. Patients with PID are ideal candidates, as they are monogenic,
the haematopoietic cells are easily obtained and virus replication is
easy within them. Vectors (viruses) "infect" the stem cells of the
patient's bone marrow, producing the transfection of the wild (healthy)
gene in these cells. Encouraging results have been achieved in X-linked
SCID as there are a number of patients who are considered "cured",
although neoplastic processes have occurred due to the activation of
proto-oncogenes close to the point of insertion of the external gene,
using retroviruses as vectors; there are now trials with adenovirus,
physical methods (direct injection...) and chemical methods (viral
modification, artificial viruses...). Gene therapy has also been
performed in patients with Chronic Granulomatous Disease and trials
will improve in the future with changes in protocols used in oncology
and infectious diseases.
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