Abstract
Increased titer of brain-directed autoantibodies (AAB) may represent a risk for brain
development in children with Rett syndrome (RTT). The aims of this work were to study
the levels of brain-directed AAB, mainly nerve growth factor (NGF) and S-100 protein
AAB, to analyze morphological features of brain labeling by AAB produced in RTT patients,
and to correlate with clinical manifestation. The increased titer of anti-NGF AAB,
but not of anti-S100 AAB has been determined in the blood of RTT patients. The blood
from five RTT girls was investigated repeatedly (two to four times) within 0.5–3 years.
In these RTT patients the level of anti-NGF AAB was stable, not depending on the stage
of illness, so individual stability of anti-NGF AAB levels have been detected. However,
the negative correlation between the level of these AAB and severity of disease has
been found: girls with the milder course of illness (with relative preservation of
speech and locomotor functions, later disease onset, and later development of regressive
symptoms) were characterized by the higher levels of AAB. The study also revealed
immunohistochemical labeling of neuronal population with serum from RTT patients.
Serum AAB from RTT cases labeled the cytoplasm and apical dendrites of pyramidal neurons
in the neocortex and hippocampus, neurons in basal ganglia and brain stem, but not
in the cerebellum of rats. Our results show the presence of brain-directed AAB in
blood serum of RTT patients, which suggests an autoimmune component in pathogenesis
of RTT.
Keywords
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© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
