Síndrome de Guillain-Barré: epidemiologia, prognóstico e fatores de risco
Introduction. Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy and the principal cause of acute neuromuscular paralysis. The most prominent GBS subtypes are: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal...
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Formato: | doctoralThesis |
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Universidade Federal do Rio Grande do Norte
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Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/20220 |
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Resumo: | Introduction. Guillain-Barré syndrome (GBS) is an immune-mediated
polyneuropathy and the principal cause of acute neuromuscular paralysis. The most
prominent GBS subtypes are: acute inflammatory demyelinating polyneuropathy
(AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal
neuropathy (AMSAN) and Fisher syndrome (FS). Differences in geographical
distribution of variants have been reported. In Brazil, there are few studies
describing the characteristics of GBS, but none on the frequency of GBS variants
and their clinical manifestations. Infection-induced aberrant immune response
resulting from molecular mimicry and formation of cross-reacting antibodies,
contribute to complement activation. Functional biallelic polymorphism in
immunoglobulin receptors that influence the affinity of IgG subclasses and the type
of immune response have been described, suggesting genetic susceptibility to
developing disease. It remains unclear whether individuals carrying different FCGR
alleles have differential risk for GBS and⁄or disease severity. The goals of this study
were: (1) To characterize GBS and describe the clinical findings in a cohort of
patients with GBS from the state of Rio Grande do Norte, Brazil; (2) to determine
whether polymorphism in FCGR were associated with development of GBS, and (3)
to tease out whether the global gene expression studies could be a tool to identify
pathways and transcriptional networks which could be regulated and decrease the
time of disease.
Methods. Clinical and laboratory data for 149 cases of GBS diagnosed from 1994
to 2013 were analyzed. Genomic DNA and total RNA were extracted from whole
blood. Antigangliosides antibodies were determined in the sera. In addition, we
also assessed whether FCGR polymorphism are present in GBS (n=141) and blood
donors (n=364), and global gene expressions were determined for 12 participants
with GBS. Blood samples were collected at the diagnosis and post-recovery.
Results. AIDP was the most frequent variant (81.8%) of GBS, followed by AMAN
(14.7%) and AMSAN (3.3%). The incidence of GBS was 0.3 ⁄ 100,000 people for
the state of Rio Grande do Norte and cases occurred at a younger age. GBS was
preceded by infections, with the axonal variant associated with episodes of diarrhea
(P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP
(P<0.0001), 84.6% of cases with the axonal variant had nadir in <10 days.
Individuals with the axonal variant took longer to recover deambulation (P<0.0001).
The mortality of GBS was 5.3%. A worse outcome was related to an axonal variant
(OR17.063; P=0.03) and time required to improve one point in the Hughes
functional scale (OR 1.028; P=0.03). The FCGR genotypes and allele frequencies
did not differ significantly between the patients with GBS and the controls (FCGR2A
p=0.367 and FCGR3A p=0.2430). Global gene expression using RNAseq showed
variation in transcript coding for protein isoforms during acute phase of disease.
Conclusions. The annual incidence of GBS was 0.3 per 100,00 and there was no
seasonal pattern. A predominance of the AIDP variant was seen, and the incidence
of the disease decreased with age. The distribution of weakness is a function of the
clinical variants, and individuals with the axonal variant had a poorer prognosis.
Early diagnosis and variant identification leads to proper intervention decreasing in
long-term morbidity. FCGR polymorphisms do not seem to influence susceptibility to
GBS in this population. This study found deregulated genes and signs of
transcriptional network alterations during the acute and recovery phases in GBS.
Identification of pathways altered during disease might be target for immune
regulation and with potential to ameliorate symptoms. |
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