Genetic association study of the HLA class II alleles DRB1, DQA1, and DQB1 in patients with pharmacoresistant temporal lobe epilepsy associated with mesial hippocampal sclerosis

Horta, Wagner G.; Paradela, Eduardo Ribeiro; Figueiredo, André; Meira, Isabella D’Andrea; Pereira, Valeska Martinho; Rêgo, Cláudia Cecília da Silva; Oliveira, Raquel; Andraus, Maria Emília Cosenza; Lacerda, Glenda Corrêa Borges de; Moura, Polyana; Souza, Jorge P. Marcondes de; Paiva, Cláudia N.; Alves-Leon, Soniza Vieira

doi:10.1016/j.seizure.2015.06.005

Cited by 10 publications

(7 citation statements)

References 21 publications

(27 reference statements)

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“…The results showed a significantly high frequency of HLA‐DQ2, HLA‐DR4, and HLA‐DR7 in this population. However, a 2015 Brazilian study failed to demonstrate any association with HLA types in the Brazilian MTLE‐HS patients.…”

Section: Discussionmentioning

confidence: 99%

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

et al. 2018

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Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is characterized by its well-defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult-onset MTLE-HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE-HS. A case-control study was carried out with 100 patients with MTLE-HS and 50 healthy controls. Sera samples from subjects were tested by indirect immunofluorescence assay for detection of anti-N-methyl-d-aspartate receptor (NMDA-R), anti-contactin-associated protein-like 2 (CASPR2), anti-leucine-rich glioma inactivated 1 (LGI1), anti-gamma aminobutyric acid B receptor (GABA-B-R), anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2 receptors (AMPA-1-R and AMPA-2-R), and enzyme-linked immunosorbent assay for detection of anti-glutamic acid decarboxylase 65 (GAD65). Mean age of patients and controls was 41.2 vs 42 years, and 55% vs 56% were female. Mean duration of epilepsy was 27.2 years. No neuronal autoantibodies were found in either group, except for anti-GAD65 in 3 patients and 2 controls. This study adds to the mounting evidence that, in Brazilian patients, MTLE-HS without signs and symptoms of autoimmune encephalitis may be infrequently associated with these autoantibodies. Differences regarding accuracy of used methodologies for autoantibody detection and genetic and environmental characteristics are discussed. Further works with different methodologies tested simultaneously in different populations may help clarify the incongruent study results about autoantibodies in MTLE-HS.

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Section: Discussionmentioning

confidence: 99%

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

et al. 2018

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“…Although the sample size is limited, our findings may suggest that a high frequency of HLA-DRB1*13 allele plays a role in the induction of hyperexcitability of the epileptic tissue. Recently, the HLA-DRB1*13:02 allele was found to be elevated in patients with MTLE-HS in comparison with controls, although the statistical significance was lost after Bonferroni correction (43). These findings may be taken into consideration as further evidence for immune-dependent genetic factors in the etiology of HS.…”

Section: Evaluation Of Cytokinesmentioning

confidence: 93%

Cytokine Polymorphism and HLA Genotyping in Patients with Temporal Lobe Epilepsy Related to Hippocampal Sclerosis

Altıntaş

Özkara

Sevindik

et al. 2017

Arch Neuropsychiatr

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Objective: Hippocampal sclerosis (HS) is the most common pathological substrate associated with mesial temporal lobe epilepsy (MTLE), where inflammatory processes are known to play an increasingly important role in the pathogenesis. To further investigate the role of the immune system, both cytokine gene polymorphisms and human leukocyte antigen (HLA) genotyping in patients with MTLE-HS were investigated.Methods: The DNA samples of 100 patients with MTLE-HS and 201 healthy individuals were genotyped for cytokines (IL-6,IL-10, TNF-ɑ, TGF-β1 and IFN-γ) and HLA using polymerase chain reaction (PCR)-SSP and SSO methods. The results were statistically analyzed in patient and healthy control groups and then according to the presence of febrile seizures (FS) in the patient group.Results: Analysis of cytokine genotyping did not reveal any significant difference between patients with MTLE-HS and controls and patients with or without FS. However, the HLA DRB1*13 allele was found to be more frequent in the patient population after Bonferroni correction.Conclusion: This study suggests the possible role of HLA in the pathogenesis of MTLE-HS, although it failed to show any relationship with the cytokine system. However, data regarding the role of HLA are still lacking, and further studies are necessary to verify our results.

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“…98 In Asian from China and Malaysia, an association of CBZ-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (SJS/TEN) with the HLA-B*1502 polymorphism has been demonstrated. 99,100 In another population with ancestral European and Japanese lineages, the HLA-A*1301 allele presented an association with drug resistance to CBZ92. 99 Other studies have attempted to identify a relationship between polymorphisms of inflammatory molecules and the development of DRE, but the results are controversial or questionable, since no other similar studies have been reported in these or other populations.…”

Section: Neuroinflammation and Bloodbrain Barrier Dysfunction In Drug...mentioning

confidence: 99%

“… 98 In Asian populations from China and Malaysia, an association of CBZ‐induced Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (SJS/TEN) with the HLA‐B*1502 polymorphism has been demonstrated. 99 , 100 In another population with ancestral European and Japanese lineages, the HLA‐A*1301 allele presented an association with drug resistance to CBZ92. 99 …”

Section: Introductionmentioning

confidence: 99%

“…CBZ‐induced hypersensitivity reactions appear to be immunologically mediated through an interaction of the drug or a drug‐related compound with major histocompatibility complex (MHC) immune receptors leading to stimulation of immune cells such as T lymphocytes and eosinophilic granulocytes 98 . In Asian populations from China and Malaysia, an association of CBZ‐induced Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (SJS/TEN) with the HLA‐B*1502 polymorphism has been demonstrated 99,100 . In another population with ancestral European and Japanese lineages, the HLA‐A*1301 allele presented an association with drug resistance to CBZ92 99 …”

Section: Introductionmentioning

confidence: 99%

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Factors not considered in the study of drug‐resistant epilepsy: Drug‐resistant epilepsy: Assessment of neuroinflammation

2022

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More than one-third of people with epilepsy develop drug-resistant epilepsy (DRE). Different hypotheses have been proposed to explain the origin of DRE.Accumulating evidence suggests the contribution of neuroinflammation, modifications in the integrity of the blood-brain barrier (BBB), and altered immune responses in the pathophysiology of DRE. The inflammatory response is mainly due to the increase of cytokines and related molecules; these molecules have neuromodulatory effects that contribute to hyperexcitability in neural networks that cause seizure generation. Some patients with DRE display the presence of autoantibodies in the serum and mainly cerebrospinal fluid. These patients are refractory to the different treatments with standard antiseizure medications (ASMs), and they could be responding well to immunomodulatory therapies. This observation emphasizes that the etiopathogenesis of DRE is involved with immunology responses and associated long-term events and chronic inflammation processes. Furthermore, multiple studies have shown that functional polymorphisms as risk factors are involved in inflammation processes.Several relevant polymorphisms could be considered risk factors involved in inflammation-related DRE such as receptor for advanced glycation end products (RAGE) and interleukin 1β (IL-1β). All these evidences sustained the hypothesis that the chronic inflammation process is associated with the DRE. However, the effect of the chronic inflammation process should be investigated in further clinical studies to promote the development of novel therapeutics useful in treatment of DRE.

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Genetic association study of the HLA class II alleles DRB1, DQA1, and DQB1 in patients with pharmacoresistant temporal lobe epilepsy associated with mesial hippocampal sclerosis

Abstract: The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS.

Cited by 10 publications

References 21 publications

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

Cytokine Polymorphism and HLA Genotyping in Patients with Temporal Lobe Epilepsy Related to Hippocampal Sclerosis

Factors not considered in the study of drug‐resistant epilepsy: Drug‐resistant epilepsy: Assessment of neuroinflammation

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