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OBJECTIVES: Nucleotide oligomerization domain (NOD) proteins are cytoplasmic receptors that play important roles in host innate immune responses to pathogens by recognizing self or non-self-molecules and have been implicated in many autoimmune diseases including Guillain-Barré syndrome (GBS). The current study investigated whether NOD polymorphisms (NOD1-Glu266Lys, rs2075820, and NOD2- [Arg702Trp, rs2066844 and Gly908Arg, rs2066845]) contribute to ligand sensing and thus affect the susceptibility and/or severity of GBS. MATERIALS AND METHODS: We determined single nucleotide polymorphisms (SNPs) of NOD gene (NOD1-Glu266Lys and NOD2-[Arg702Trp; Gly908Ar]) in 303 patients with GBS and 303 healthy controls from Bangladesh by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. Genotypes and allele frequencies were compared by performing chi-squared or Fisher's exact test with Yates' continuity correction. Serology for Campylobacter jejuni and anti-GM1 antibodies were determined by enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: NOD variants (NOD1-Glu266Lys and NOD2- [Arg702Trp; Gly908Arg]) were not associated with susceptibility and severity of GBS when compared with healthy controls and mild or severe form of disease. Moreover, NOD2 polymorphisms showed wild-type NOD2 C2104 and NOD2 G2722, respectively, with homozygous Arg/Arg genotype of NOD2 (Arg702Trp) polymorphism and homozygous Gly/Gly genotype of NOD2 (Gly908Arg) for all study subjects in Bangladesh. Homogenous distribution of NOD1 genotypes was observed in patients with axonal and demyelinating form of GBS. CONCLUSIONS: NOD variants confer no risk to the susceptibility and severity of GBS. Moreover, NOD2 polymorphism is rare or absent in patients with GBS as well as in the healthy individuals of Bangladesh.
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Síndrome de Guillain-Barré , Nucleótidos , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Síndrome de Guillain-Barré/genética , Humanos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. The objective of this study was to investigate the preceding infections, clinical, serological and electrophysiological characteristics and outcome of childhood GBS in Bangladesh. We included 174 patients with GBS aged <18 years from a prospective cohort in Bangladesh between 2010 and 2018. We performed multivariate logistic regression to determine the risk factors for poor outcome. Among 174 children with GBS, 74% (n = 129) were male. Around half of the patients (49%, n = 86) had severe muscle weakness, 65% (n = 113) were bedbound (GBS disability score 4) and 17% (n = 29) patients required mechanical ventilation at admission. Campylobacter jejuni serology and anti-GM1 IgG antibody were positive in 66% and 21% of the patients respectively. One hundred and forty-three (82%) patients did not receive standard treatment and half of them recovered fully or with minor deficits at 6-month. Twenty patients (11%) died throughout the study period. At 3-month of onset of weakness, complete recovery or recovery with minor deficit was significantly higher in demyelinating GBS patients compared to axonal GBS patients (86% vs 51%, P = .001). Cranial nerve palsy (OR = 4.00, 95%CI = 1.55-10.30, P = .004) and severe muscle weakness (OR = 0.16, 95%CI = 0.06-0.45, P = .001) were the important risk factors of poor outcome in children with GBS. Further large-scale studies are required for better understanding of factors associated with mortality and morbidity in childhood GBS.
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Anticuerpos Antibacterianos/sangre , Autoanticuerpos/sangre , Enfermedades de los Nervios Craneales , Síndrome de Guillain-Barré , Debilidad Muscular , Adolescente , Bangladesh , Campylobacter jejuni/inmunología , Niño , Preescolar , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/etiología , Enfermedades de los Nervios Craneales/fisiopatología , Femenino , Gangliósidos/inmunología , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/fisiopatología , Humanos , Lactante , Masculino , Debilidad Muscular/diagnóstico , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Several published reports have described a possible association between Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This systematic review aimed to summarize and meta-analyze the salient features and prognosis of SARS-CoV-2-associated GBS. We searched the PubMed (Medline), Web of Science and Cochrane databases for articles published between 01 January 2020 and 05 August 2020 using SARS-CoV-2 and GBS-related keywords. Data on sociodemographic characteristics, antecedent symptoms, clinical, serological and electrophysiological features, and hospital outcomes were recorded. We included 45 articles from 16 countries reporting 61 patients with SARS-CoV-2-associated GBS. Most (97.7%) articles were from high- and upper-middle-income countries. Forty-two (68.9%) of the patients were male; median (interquartile range) age was 57 (49-70) years. Reverse transcriptase polymerase chain reaction for SARS-CoV-2 was positive in 90.2% of patients. One report of SARS-CoV-2-associated familial GBS was found which affected a father and daughter of a family. Albuminocytological dissociation in cerebrospinal fluid was found in 80.8% of patients. The majority of patients (75.5%) had a demyelinating subtype of GBS. Intravenous immunoglobulin and plasmapheresis were given to 92.7% and 7.3% of patients, respectively. Around two-thirds (65.3%) of patients had a good outcome (GBS-disability score ≤ 2) on discharge from hospital. Two patients died in hospital. SARS-CoV-2-associated GBS mostly resembles the classical presentations of GBS that respond to standard treatments. Extensive surveillance is required in low- and lower-middle-income countries to identify and report similar cases/series. Further large-scale case-control studies are warranted to strengthen the current evidence. PROSPERO Registration Number CRD42020201673.
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COVID-19/complicaciones , Síndrome de Guillain-Barré/virología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
OBJECTIVE: Interleukin-10 (IL-10) is a multifunctional cytokine that exerts both pro- and anti-inflammatory effects on the immune system as well as in the pathogenesis of Guillain-Barré syndrome (GBS). We investigated whether the three common polymorphisms -1082 G/A(rs1800896), -819 C/T(rs1800871), and -592 C/A(rs1800872) in the promoter region of IL-10 have any influence on the susceptibility, severity, and clinical outcome of GBS. METHODS: IL-10 promoter polymorphisms were investigated in 152 patients with GBS and 152 healthy controls from Bangladesh using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and allele-specific oligonucleotide-PCR (ASO-PCR). Haplotype patterns and frequencies were analyzed using Heatmaply R-package, chi-square, and Fisher's exact test. The serum level of IL-10 was measured through enzyme-linked immunosorbent assays. p-values < 0.05 were considered statistically significant. RESULTS: IL-10 promoter polymorphisms -1082 G/A, -819 C/T, and -592 C/A were not associated with GBS susceptibility. The homozygous -819 TT genotype showed a tendency with susceptibility (p = 0.029; pc = 0.08) and was prevalent in axonal variants of GBS compared to demyelinating subtypes and controls (p = 0.042, OR = 8.67, 95% CI = 1.03-72.97; pc = 0.123 and p = 0.005, OR = 4.2, 95% CI = 1.55-11.40; pc = 0.015, respectively). Haplotype analysis revealed 19 patterns of genotypes and high IL-10 expression haplotype combinations (GCC/GTA, GCC/ATA, and GCC/GCA) may have influence on disease severity (p = 0.026; pc = 0.078). Serum expression of IL-10 was elevated in GBS patients ([GBS, 12.16 ± 45.71] vs. [HC, 0.65 ± 5.17] pg/mL; p = 0.0027) and varied with disease severity ([severe-GBS, 15.25 ± 51.72] vs. [mild-GBS, 3.59 ± 19.79] pg/mL, p = 0.046). INTERPRETATION: The -819 TT genotypes influence axonal GBS, and high frequency of IL-10 expression haplotype combination with elevated serum IL-10 may play an important role in disease severity.
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Síndrome de Guillain-Barré , Interleucina-10 , Humanos , Predisposición Genética a la Enfermedad/genética , Síndrome de Guillain-Barré/genética , Haplotipos , Interleucina-10/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genéticaRESUMEN
Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.
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Disentería Bacilar , Shigella , Niño , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Disentería Bacilar/tratamiento farmacológico , Disentería Bacilar/epidemiología , Macrólidos/farmacología , Macrólidos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Azitromicina/farmacología , Azitromicina/uso terapéutico , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Ceftriaxona/farmacología , Pruebas de Sensibilidad Microbiana , Inhibidores de la Síntesis de la Proteína/farmacología , Plásmidos/genéticaRESUMEN
Shigellosis remains a common gastrointestinal disease mostly in children <5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.
RESUMEN
Shigella is the second leading cause of diarrheal deaths worldwide. Azithromycin (AZM) is a potential treatment option for Shigella infection; however, the recent emergence of AZM resistance in Shigella threatens the current treatment strategy. Therefore, we conducted a comprehensive whole genome-based approach to identify the mechanism(s) of AZM resistance in Shigella. We performed antimicrobial susceptibility tests, polymerase chain reaction (PCR), Sanger (amplicon) sequencing, and whole genome-based bioinformatics approaches to conduct the study. Fifty-seven (38%) of the Shigella isolates examined were AZM resistant; Shigella sonnei exhibited the highest rate of resistance against AZM (80%). PCR amplification for 15 macrolide resistance genes (MRGs) followed by whole-genome analysis of 13 representative Shigella isolates identified two AZM-modifying genes, mph(A) (in all Shigella isolates resistant to AZM) and mph(E) (in 2 AZM-resistant Shigella isolates), as well as one 23S rRNA-methylating gene, erm(B) (41% of AZM-resistant Shigella isolates) and one efflux pump mediator gene, msr(E) [in the same two Shigella isolates that harbored the mph(E) gene]. This is the first report of msr(E) and mph(E) genes in Shigella. Moreover, we found that an IncFII-type plasmid predominates and can possess all four MRGs. We also detected two plasmid-borne resistance gene clusters: IS26-mph(A)-mrx(A)-mph(R)(A)-IS6100, which is linked to global dissemination of MRGs, and mph(E)-msr(E)-IS482-IS6, which is reported for the first time in Shigella. In conclusion, this study demonstrates that MRGs in association with pathogenic IS6 family insertion sequences generate resistance gene clusters that propagate through horizontal gene transfer (HGT) in Shigella. IMPORTANCE Shigella can frequently transform into a superbug due to uncontrolled and rogue administration of antibiotics and the emergence of HGT of antimicrobial resistance factors. The advent of AZM resistance in Shigella has become a serious concern in the treatment of shigellosis. However, there is an obvious scarcity of clinical data and research on genetic mechanisms that induce AZM resistance in Shigella, particularly in low- and middle-income countries. Therefore, this study is an approach to raise the alarm for the next lifeline. We show that two key MRGs [mph(A) and erm(B)] and the newly identified MRGs [mph(E) and msr(E)], with their origination in plasmid-borne pathogenic islands, are fundamental mechanisms of AZM resistance in Shigella in Bangladesh. Overall, this study predicts an abrupt decrease in the effectiveness of AZM against Shigella in the very near future and suggests prompt focus on seeking a more effective treatment alternative to AZM for shigellosis.
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Disentería Bacilar , Shigella , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Bangladesh , Farmacorresistencia Bacteriana/genética , Disentería Bacilar/tratamiento farmacológico , Humanos , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Shigella/genéticaRESUMEN
Four Campylobacter jejuni strains (Z191005RS, Z191005SS, Z201020RS, and Z201020SS) isolated from the axonal variant of Guillain-Barré syndrome (GBS) were sequenced using Illumina technology. The average genome size was from 1.61 to 1.63 gb, with a very high coverage ranging from 654× to 758×, which facilitates the possibility of rare variant calling.
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Complement activation plays a critical role in the pathogenesis of Guillain-Barré syndrome (GBS), a debilitating immune-mediated neuropathy. Mannose-binding lectin (MBL) is a complement activation factor of lectin pathway which as genetic host factor may influence the susceptibility or severity of GBS. We investigated the frequency of MBL2 promoter (- 550H/L and - 221X/Y) and functional region (exon 1 A/O) polymorphisms and their association with disease susceptibility, clinical features and serum MBL among GBS patients (n = 300) and healthy controls (n = 300) in Bangladesh. The median patient age was 30 years (IQR: 18-42; males, 68%). MBL2 polymorphisms were not significantly associated with GBS susceptibility compared to healthy controls. HL heterozygosity in GBS patients was significantly associated with mild functional disability at enrolment (P = 0.0145, OR, 95% CI 2.1, 1.17-3.82). The HY, YA, HA and HYA heterozygous haplotypes were more common among mildly affected (P = 0.0067, P = 0.0086, P = 0.0075, P = 0.0032, respectively) than severely affected patients with GBS. Reduced serum MBL was significantly associated with the LL, OO and no HYA variants and GBS disease severity. No significant association was observed between MBL2 polymorphisms and electrophysiological variants, recent Campylobacter jejuni infection or anti-ganglioside (GM1) antibody responses in GBS. In conclusion, MBL2 gene polymorphisms are related to reduced serum MBL and associated with the severity of GBS.
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Síndrome de Guillain-Barré , Lectina de Unión a Manosa , Adolescente , Adulto , Activación de Complemento , Exones , Predisposición Genética a la Enfermedad , Genotipo , Síndrome de Guillain-Barré/genética , Haplotipos , Humanos , Masculino , Lectina de Unión a Manosa/genética , Polimorfismo Genético , Adulto JovenRESUMEN
The emergence of multidrug-resistant (MDR) Shigella strains has impaired the efficacy of first-line antimicrobials and exacerbated diarrhea-associated morbidity and mortality worldwide. We report the draft genome sequences of 11 MDR Shigella strains isolated from the stool specimens of diarrheal patients in Bangladesh.
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A 50-years old male presented with quadriplegia and paresthesia and was diagnosed as Guillain-Barré syndrome (GBS). He was found positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) six weeks prior to the onset of weakness. GBS disability score was 4. Electrophysiology showed acute inflammatory demyelinating polyradiculopathy. Anti-SARS-CoV-2 IgG was found positive. Immunological tests for Campylobacter jejuni, Zika virus, Hepatitis E virus, Herpes Simplex virus, Haemophilus influanzae and Mycoplasma pneumoniae were negative. Patient received standard dose of intravenous immunoglobulin and after six months had almost complete recovery of muscle power. This case represents possible association of SARS-CoV-2 infection and GBS with good clinical outcome.
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COVID-19/complicaciones , Síndrome de Guillain-Barré/virología , Estudios de Seguimiento , Síndrome de Guillain-Barré/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , SARS-CoV-2 , TiempoRESUMEN
Campylobacter jejuni is the pathogen most commonly associated with Guillain-Barré syndrome (GBS). The present work describes the draft genome sequences of 3 C. jejuni strains, BD39, BD67, and BD75, isolated from stool specimens of patients with C. jejuni-triggered GBS using Illumina technologies.
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Guillain-Barré syndrome (GBS) is an immune-mediated paralytic disorder. Glucocorticoid receptor (GR) gene polymorphisms affect the sensitivity to glucocorticoids and have been related to microbial colonization and infection, and thereby may influence susceptibility to GBS. The associations between GR polymorphisms (ER22/23EK, N363S, BclI, TthIII-1 and GR-9beta) and development of GBS were investigated in 151 patients and 151 healthy controls. GR polymorphisms or haplotypes were not associated with GBS susceptibility. Haplotype 1 (TthIII-1[T/T]:BclI[G/G]:GR-9beta[A/A]) was less common in GBS; but not statistically significant after correction (P = 0.021; Pc = 0.108). The GR-9beta(G/A) and TthIII-1(C/T) genotypes were frequent in anti-GM1-antibody-positive patients than anti-GM1-antibody-negative patients (P = 0.017 and P = 0.030, respectively).
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Predisposición Genética a la Enfermedad/genética , Síndrome de Guillain-Barré/genética , Receptores de Glucocorticoides/genética , Adolescente , Adulto , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
OBJECTIVE: Guillain-Barré syndrome (GBS) is a rare, life-threatening disorder of the peripheral nervous system. Immunoglobulin G Fc-gamma receptors (FcγRs) mediate and regulate diverse effector functions and are involved in the pathogenesis of GBS. We investigated whether the FcγR polymorphisms FcγRIIa H/R131 (rs1801274), FcγRIIIa V/F158 (rs396991), and FcγRIIIb NA1/NA2, and their haplotype patterns affect the affinity of IgG-FcγR interactivity and influence GBS susceptibility and severity. METHODS: We determined FcγR polymorphisms in 303 patients with GBS and 302 ethnically matched healthy individuals from Bangladesh by allele-specific polymerase chain reaction. Pairwise linkage disequilibrium and haplotype patterns were analyzed based on D Ìstatistics and the genotype package of R statistics, respectively. Logistic regression analysis and Fisher's exact test with corrected P (Pc) values were employed for statistical comparisons. RESULTS: FcγRIIIa-V158F was associated with the severe form of GBS compared to the mild form (P = 0.005, OR = 2.24, 95% CI = 1.28-3.91; Pc = 0.015); however, FcγR genotypes and haplotype patterns did not show any association with GBS susceptibility compared to healthy controls. FcγRIIIa-V/V158 and FcγRIIIb-NA2/2 were associated with recent Campylobacter jejuni infection (P ≤ 0.001, OR = 0.36, 95% CI = 0.23-0.56; Pc ≤ 0.003 and P = 0.004, OR = 1.70, 95% CI = 1.18-2.44; Pc ≤ 0.012, respectively). Haplotype 1 (FcγRIIa-H131R- FcγRIIIa-V158F- FcγRIIIb-NA1/2) and the FcγRIIIb-NA2/2 genotype were more prevalent among anti-GM1 antibody-positive patients (P = 0.031, OR = 9.61, 95% CI = 1.24-74.77, Pc = 0.279; P = 0.027, OR = 1.62, 95% CI = 1.06-2.5, Pc = 0.081, respectively). INTERPRETATION: FcγR polymorphisms and haplotypes are not associated with susceptibility to GBS, though the FcγRIIIa-V158F genotype is associated with the severity of GBS.
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Predisposición Genética a la Enfermedad , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/fisiopatología , Receptores de IgG/genética , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Femenino , Proteínas Ligadas a GPI/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Adulto JovenRESUMEN
Guillain-Barré syndrome (GBS) is an immune-mediated neurological disorder with a multifaceted nature. Infectious agents and immune-response genetic host factors may contribute to the development of GBS. The matrix metalloproteinase-9 (MMP-9), an enzyme is upregulated by pro-inflammatory cytokines and might play an important role in the pathogenesis of GBS. This study investigated the association of a single nucleotide polymorphism (-1562C/T, rs3918242) in the MMP9 gene with the susceptibility and severity of GBS in Bangladesh. The allele and genotype distributions of the MMP9 polymorphism were not significantly different between 303 patients with GBS and 303 healthy controls. Serum concentrations of MMP-9 were significantly elevated in patients with GBS compared to healthy controls (P ≤.0001). No significant association of MMP-9 (-1562C/T) polymorphism was observed with disease prognosis. The frequencies of the MMP9-1562 CT genotype and T allele (P = .01, OR = 2.28, 95% CI = 1.22-4.22; Pc = 0.03 and P = .012, OR = 2.0, 95% CI = 1.14-3.38; Pc = 0.024, respectively) were significantly increased in patients with severe form of GBS, indicates the MMP9 polymorphism plays a role in the disease severity of GBS.
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Síndrome de Guillain-Barré , Metaloproteinasa 9 de la Matriz , Alelos , Predisposición Genética a la Enfermedad , Genotipo , Síndrome de Guillain-Barré/genética , Humanos , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: The etiology of Guillain-Barré syndrome (GBS) remains enigmatic, although genetic and environmental factors are speculated to be associated with this autoimmune condition. We investigated whether polymorphisms and the haplotype structures of the human leukocyte antigen (HLA)-DQB1 gene relate to the autoimmune response to infection and affect the development of GBS. METHODS: HLA-DQB1 polymorphic alleles (*0201, *030x, *0401, *050x, *060x) were determined for 151 Bangladeshi patients with GBS and 151 ethnically matched healthy controls using sequence-specific polymerase chain reaction. Pairwise linkage disequilibrium (LD) and haplotype patterns were analyzed based on D Ìstatistics and the genotype package in R statistics, respectively. Association studies were conducted using Fisher's exact test and logistic regression analysis. The Bonferroni method was applied to correct for multiple comparisons, whereby the P-value was multiplied with the number of comparisons and denoted as Pc (Pc, P corrected). RESULTS: No associations were observed between HLA-DQB1 alleles and susceptibility to disease in the comparison between GBS patients and healthy subjects. Haplotype 9 (DQB1*0303-*0601) tended to be less frequent among patients with GBS than healthy controls (P = 0.006, OR = 0.49, 95% CI = 0.30-0.82; Pc = 0.06). Haplotype 5 (DQB1*0501-*0602) and the DQB1*0201 alleles were more frequent in the Campylobacter jejuni-triggered axonal variant of GBS (P = 0.024, OR = 4.06, 95% CI = 1.25-13.18; Pc = 0.24) and demyelinating subtype (P = 0.027, OR = 2.68, 95% CI = 1.17-6.17; Pc = 0.35), though these associations were not significant after Bonferroni correction. INTERPRETATION: This study indicates that HLA-DQB1 polymorphisms are not associated with susceptibility to GBS. In addition, these genetic markers did not influence the clinical features or serological subgroup in patients with C. jejuni-triggered axonal variant of GBS.
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Síndrome de Guillain-Barré/genética , Cadenas beta de HLA-DQ/genética , Haplotipos , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Síndrome de Guillain-Barré/inmunología , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: TLR4 plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS). The relationships between TLR4 polymorphisms and susceptibility to GBS are poorly understood. We investigated the frequency and assessed the association of two single nucleotide polymorphisms (SNPs) in the extracellular domain of TLR4 (Asp299Gly and Thr399Ile) with disease susceptibility and the clinical features of GBS in a Bangladeshi cohort. METHODS: A total of 290 subjects were included in this study: 141 patients with GBS and 149 unrelated healthy controls. The TLR4 polymorphisms Asp299Gly and Thr399Ile were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The minor 299Gly allele was significantly associated with GBS susceptibility (P = 0.0137, OR = 1.97, 95% CI = 1.17-3.31), and was present at a significantly higher frequency in patients with the acute motor axonal neuropathy (AMAN) subtype of GBS (P = 0.0120, OR = 2.37, 95% CI = 1.26-4.47) than acute inflammatory demyelinating polyneuropathy (AIDP) subtype (P = 0.961, OR = 1.15, 95% CI = 0.38-3.48); when compared to healthy controls. The genotype frequency of the Asp299Gly polymorphism was not significantly different between patients with GBS and healthy controls. The Asp299-Thr399 haplotype was associated with a significantly lower risk of developing GBS (P = 0.0451, OR = 0.63, 95% CI = 0.40-0.99). No association was observed between the Thr399Ile polymorphism and GBS disease susceptibility. INTERPRETATION: The TLR4 minor 299Gly allele was associated with increased susceptibility to GBS and the axonal GBS subtype in the Bangladeshi population. However, no associations were observed between the genotypes of the Asp299Gly and Thr399Ile SNPs and antecedent C. jejuni infection or disease severity in Bangladeshi patients with GBS.