RESUMEN
OBJECTIVE: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak. METHODS: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates. RESULTS: The 49 included patients had a median age of 44 years (interquartile range [IQR] 30-54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2-9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2-9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene. CONCLUSIONS: Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world.
Asunto(s)
Infecciones por Campylobacter/diagnóstico , Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/aislamiento & purificación , Brotes de Enfermedades , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiología , Adulto , Infecciones por Campylobacter/sangre , Estudios de Casos y Controles , Femenino , Síndrome de Guillain-Barré/sangre , Humanos , Masculino , Persona de Mediana Edad , Perú/epidemiologíaRESUMEN
Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients.
Asunto(s)
Gangliósidos/inmunología , Síndrome de Guillain-Barré/sangre , Infección por el Virus Zika/sangre , Virus Zika/fisiología , Autoanticuerpos , Brasil , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virologíaRESUMEN
The role of neutralizing antibodies in Zika-induced Guillain-Barré syndrome (GBS) has not yet been investigated. We conducted a case-control study using sera from the 2016 Zika epidemic in Colombia to determine the neutralizing antibody activity against Zika virus (ZIKV) and dengue virus serotype 2 (DENV2). We observed increased neutralizing antibody titers against DENV2 in ZIKV-infected individuals compared with uninfected controls and higher titers to both ZIKV and DENV2 in ZIKV-infected patients diagnosed with GBS compared with non-GBS ZIKV-infected controls. These data suggest that high neutralizing antibody titers to DENV and to ZIKV are associated with GBS during ZIKV infection.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Dengue/sangre , Síndrome de Guillain-Barré/sangre , Infección por el Virus Zika/sangre , Adulto , Estudios de Casos y Controles , Colombia/epidemiología , Dengue/complicaciones , Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Femenino , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/virología , Humanos , Masculino , Persona de Mediana Edad , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/inmunologíaRESUMEN
In countries where poliomyelitis has been eradicated, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. The range of infections that precede GBS in Brazil is unknown. Campylobacter jejuni infection is the most frequent trigger of GBS worldwide. Given the lack of systematic surveillance of diarrheal diseases, particularly in adults, the incidence of enteritis caused by C. jejuni in developing countries is unknown. From 2014 to 2016, pretreatment serum samples from 63 GBS patients were tested by immunoglobulin M (IgM) enzyme-linked immunosorbent assay for C. jejuni. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the samples. There was no association between serological positivity (IgM) for C. jejuni and the occurrence of diarrhea among the investigated cases (P = 0.36). Hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin may help prevent acute flaccid paralysis.
Asunto(s)
Biomarcadores/análisis , Infecciones por Campylobacter/diagnóstico , Síndrome de Guillain-Barré/etiología , Adulto , Biomarcadores/sangre , Brasil , Infecciones por Campylobacter/sangre , Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/patogenicidad , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodosRESUMEN
The purpose of this study was to investigate the prognostic value of the pretreatment and post-treatment albumin level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in subtypes of Guillain-Barré syndrome (GBS). A retrospective analysis of 62 patients with GBS treated between 2011 and 2015 in Dicle University Hospital, Turkey, was carried out. The pretreatment and post-treatment albumin, NLR, and PLR were documented, together with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, motor sensory axonal neuropathy, and Hughes' scores. Post-treatment albumin levels in GBS were significantly reduced, and albumin level was negatively correlated with the Hughes scores. Elevated pretreatment NLRs and PLRs were significantly associated with AIDP. There were no correlations between the Hughes scores, NLR, and PLR. The results point to a negative correlation between albumin levels and GBS disability and suggest that the NLR and PLR may be promising blood biomarkers of AIDP.
Asunto(s)
Plaquetas , Síndrome de Guillain-Barré/sangre , Linfocitos , Neutrófilos , Albúmina Sérica/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Recuento de Células Sanguíneas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
The pathogenesis of Guillain-Barré Syndrome (GBS) is not entirely understood, but includes infection-induced aberrant immune responses. Genetic polymorphisms in Fc gamma receptor genes (FCGR) have been associated with GBS. We assessed whether polymorphisms rs1801274 in FCGR2A and rs396991 in FCGR3A were associated with GBS in a Brazilian population. We genotyped 141 GBS cases and 364 healthy controls from Brazil for both polymorphisms. The FCGR genotypes and alleles frequencies did not differ significantly between GBS and controls. In addition, there was no genetic association with either severity or clinical outcomes. We conclude that these FCGR polymorphisms are not associated with susceptibility to Guillain-Barré Syndrome in this Brazilian population.
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Síndrome de Guillain-Barré/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de IgG/genética , Adulto , Anticuerpos/sangre , Brasil , Femenino , Gangliósidos/inmunología , Estudios de Asociación Genética , Genotipo , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
ABSTRACT The purpose of this study was to investigate the prognostic value of the pretreatment and post-treatment albumin level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in subtypes of Guillain-Barré syndrome (GBS). A retrospective analysis of 62 patients with GBS treated between 2011 and 2015 in Dicle University Hospital, Turkey, was carried out. The pretreatment and post-treatment albumin, NLR, and PLR were documented, together with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, motor sensory axonal neuropathy, and Hughes’ scores. Post-treatment albumin levels in GBS were significantly reduced, and albumin level was negatively correlated with the Hughes scores. Elevated pretreatment NLRs and PLRs were significantly associated with AIDP. There were no correlations between the Hughes scores, NLR, and PLR. The results point to a negative correlation between albumin levels and GBS disability and suggest that the NLR and PLR may be promising blood biomarkers of AIDP.
RESUMO O objetivo deste estudo foi investigar o valor prognóstico dos níveis pré e pós-tratamento de albumina , da relação neutrófilo/linfócito (RNL) e da relação plaqueta/linfócito (RPL) em subtipos de síndrome de Guillain-Barré (SGB). Realizou-se uma análise retrospectiva de 62 pacientes com GBS, tratados entre 2011 e 2015 no Hospital da Universidade Dicle, na Turquia. Os valores pré e pós-tratamento de albumina, RNL e RPL foram documentados, juntamente com polirradiculoneuropatia desmielinizante inflamatória aguda, (PDIA) neuropatia axonal motora aguda, neuropatia axonal sensorial motora e pontuações de Hughes. Os níveis de albumina reduziram significativamente pós-tratamento e correlacionaram-se negativamente com as pontuações de Hughes. RNLs e RPLs pré-tratamento elevados foram significativamente associados à PDIA. Não houve correlação entre as pontuações de Hughes, RNL e RPL. Os resultados apontam uma correlação negativa entre os níveis de albumina e a deficiência na SGB e sugerem que a RNL e a RPL possam ser promissores biomarcadores sanguíneos para PDIA.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Plaquetas , Albúmina Sérica/análisis , Linfocitos , Síndrome de Guillain-Barré/sangre , Neutrófilos , Pronóstico , Valores de Referencia , Recuento de Células Sanguíneas , Biomarcadores/sangre , Estudios Retrospectivos , Análisis de Varianza , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index. OBJECTIVES: To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance. METHODS: CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barré syndrome. RESULTS: All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies. CONCLUSIONS: Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.
Asunto(s)
Anticuerpos Antivirales/líquido cefalorraquídeo , Virus del Dengue/inmunología , Dengue/inmunología , Encefalitis Viral/inmunología , Síndrome de Guillain-Barré/inmunología , Mielitis/inmunología , Neuritis Óptica/inmunología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Dengue/sangre , Dengue/líquido cefalorraquídeo , Encefalitis Viral/sangre , Encefalitis Viral/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Femenino , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/líquido cefalorraquídeo , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina M/sangre , Inmunoglobulina M/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Mielitis/sangre , Mielitis/líquido cefalorraquídeo , Neuritis Óptica/sangre , Neuritis Óptica/líquido cefalorraquídeo , Estudios Retrospectivos , Adulto JovenRESUMEN
Anti-GM1 antibodies of the IgG isotype are found in serum from patients with Guillain-Barré syndrome. In normal human sera, anti-GM1 IgM-antibodies are commonly present, but their IgG counterpart has not been previously demonstrated. During routine screening, we found a normal human serum with a high titer of anti-GM1 IgG-antibodies (IgG1 subclass). Affinity estimation by soluble antigen-binding inhibition indicated that they are low-affinity antibodies with IC50 values between one and two orders of magnitude higher than those of anti-GM1 IgG-antibodies from Guillain-Barré patients. Various antibody parameters remained fairly constant for 1 year, in additional serum samples taken at 4-month intervals. Such anti-GM1 IgG1-antibodies were not detected in > 100 other normal serum samples tested, indicating a very low frequency in the general population. The low affinity of these unusually present antibodies could explain the absence of disease, despite their relatively high titer. The significance of this finding in the origin of disease-associated anti-GM1 antibodies is discussed.
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Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Gangliósido G(M1)/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adulto , Afinidad de Anticuerpos , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Femenino , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/inmunología , HumanosRESUMEN
Elevated titers of serum anti-GM(1) antibodies of IgG isotype are found frequently in patients with Guillain-Barré syndrome. Much evidence indicates that these autoantibodies are involved in disease progression, but their exact function and the mechanism of their appearance are still unclear. In an attempt to reproduce "ganglioside syndrome", the experimental model of neuropathy developed by Nagai et al. (Neurosci. Lett. 2 (1976) 107), rabbits were intensively immunized with GM(1) in complete Freund adjuvant (CFA). High titers of anti-GM(1) antibodies were produced, with class switch and affinity maturation indicating an elaborate immune response. Unexpectedly, the rabbits did not show any clinical symptoms of neuropathy. Relatively affinities of both IgM and IgG antibodies were significantly lower than those of similar antibodies from neuropathy patients. These results suggest the existence of a threshold value above which affinity of anti-GM(1) antibodies becomes an important factor in disease induction. The absence of neuropathy symptoms in rabbits may be explained by absence of these high-affinity anti-GM(1) antibodies.