scholarly journals Significant Association ofHLA-BAlleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Apichaya Puangpetch ◽  
Pongwut Suwannarat ◽  
Montri Chamnanphol ◽  
Napatrupron Koomdee ◽  
Nattawat Ngamsamut ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Human Leukocyte ◽  
Normal Subjects ◽  
Protective Role ◽  
Autism Spectrum ◽  
Thai Population ◽  
Leukocyte Antigen ◽  
Specific Oligonucleotide Probe ◽  
Sequence Specific Oligonucleotide Probe ◽  
The Relationship

Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identifyHLA-Balleles associated with autism in Thai population, we compared the frequency ofHLA-Ballele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology.HLA-B⁎13:02(P=0.019, OR = 2.229),HLA-B⁎38:02(P=0.049, OR = 1.628),HLA-B⁎44:03(P=0.016, OR = 1.645), andHLA-B⁎56:01(P= 1.78 × 10−4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that theHLA-B⁎18:02(P=0.016, OR = 0.375) andHLA-B⁎46:12(P=0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, fourHLA-Bgenotypes of autistic patients had statistically significant relationship with control groups, consisting ofHLA-B⁎3905/⁎5801(P=0.032, OR = 24.697),HLA-B⁎2704/⁎5801(P=0.022, OR = 6.872),HLA-B⁎3501/⁎4403(P=0.021, OR = 30.269), andHLA-B⁎1801/⁎4402(P = 0.017, OR = 13.757). This is the first report onHLA-Bassociated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population.

scholarly journals Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis

2021 ◽  
Author(s):  
Chonlaphat Sukasem ◽  
Suthida Sririttha ◽  
Chonlawat Chaichan ◽  
Thapanat Nakkrut ◽  
Patompong Satapornpong ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Antiepileptic Drugs ◽  
Meta Analysis ◽  
Strong Association ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Thai Population ◽  
Leukocyte Antigen ◽  
Maculopapular Eruption ◽  
Sequence Specific Oligonucleotide Probe

AbstractAromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

scholarly journals CHD8 regulates gut epithelial cell function and affects autism-related behaviours through the gut-brain axis

2021 ◽  
Author(s):  
Ipsita Chaterjee ◽  
Dmitriy Getselter ◽  
Nasreen Ghaneem ◽  
Shai Bel ◽  
Evan Elliott
Keyword(s):  
Epithelial Cells ◽  
Cell Function ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Direct Role ◽  
Tuft Cells ◽  
Core Symptoms ◽  
The Relationship ◽  
Specific Deletion

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early onset deficits in social behavior and repetitive behavior. Chromodomain helicase DNA binding protein (CHD8) is one of the genes with the strongest association to autism. Alongside with the core symptoms of ASD, individuals with ASD are reported to have gastrointestinal (GI) problems, and a majority of individuals with CHD8 mutations display GI problems. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviours are yet very unclear. In the current study, we found that mice haploinsufficient for CHD8 have leaky gut, a dysregulated transcriptome in gut epithelial cells, decreased gut tuft cells and goblet cells, and an increase in microbial load. Specific deletion of CHD8 in gut epithelial cells induced an increase in anxiety-related behaviours in, a phenotype that is often observed in autism and full body knockdown of CHD8, in addition to decreased tuft cells. In addition, antibiotic treatment of CHD8 haploinsufficient mice attenuates sociability deficits. Therefore, the current study determines a pathway for autism-related GI deficits, and how these deficits may play a direct role in the development of autism-related behaviours.

scholarly journals Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation

2020 ◽  
Vol 9 (12) ◽  
pp. 3986
Author(s):  
Sinem Ünlü ◽  
Nils Lachmann ◽  
Maximilian Jara ◽  
Paul Viktor Ritschl ◽  
Leke Wiering ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Causes Of Death ◽  
Human Leukocyte ◽  
Infectious Complications ◽  
Control Group ◽  
Leukocyte Antigen ◽  
High Urgency ◽  
Donor Specific Antibodies ◽  
One Year ◽  
The Relationship

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

scholarly journals Fetal cell microchimerism: a protective role in autoimmune thyroid diseases

2015 ◽  
Vol 173 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Valentina Cirello ◽  
Roberta Rizzo ◽  
Milena Crippa ◽  
Irene Campi ◽  
Daria Bortolotti ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Protective Role ◽  
Systemic Autoimmune Disease ◽  
Fetal Cell ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Leukocyte Antigen ◽  
Fetal Cells ◽  
Maternal Immune System ◽  
Polymorphic Pattern

ObjectiveThe physiological persistence of fetal cells in the circulation and tissue of a previously pregnant woman is called fetal cell microchimerism (FCM). It has been hypothesized to play a role in systemic autoimmune disease; however, only limited data are available regarding its role in autoimmune thyroid disease (AITD).DesignCirculating FCM was analyzed in a large series of previously pregnant women with Graves' disease (GD), Hashimoto's thyroiditis (HT), or no disease (healthy controls (HCs)). To exclude the possible bias related to placental factors, the polymorphic pattern of human leukocyte antigen-G (HLA-G) gene, which is known to be involved in the tolerance of fetal cells by the maternal immune system, was investigated.MethodsFCM was evaluated by PCR in the peripheral blood, and the Y chromosome was identified by fluorescencein situhybridization in some GD tissues.HLA-Gpolymorphism typing was assessed by real-time PCR.ResultsFCM was significantly more frequent in HC (63.6%) than in GD (33.3%) or HT (27.8%) women (P=0.0004 andP=0.001 respectively). A quantitative analysis confirmed that circulating male DNA was more abundant in HC than it was in GD or HT. Microchimeric cells were documented in vessels and in thyroid follicles. In neither GD/HT patients nor HC women was theHLA-Gtyping different between FCM-positive and FCM-negative cases.ConclusionThe higher prevalence of FCM in HC as compared to GD and HT patients suggests that it plays a possible protective role in autoimmune thyroid disorders. Placental factors have been excluded as determinants of the differences found. The vascular and tissue localization of microchimeric cells further highlights the ability of those cells to migrate to damaged tissues.

scholarly journals The relationship of Rett syndrome and MECP2 disorders to autism

2012 ◽  
Vol 14 (3) ◽  
pp. 253-262 ◽  
Keyword(s):  
Rett Syndrome ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Protein Product ◽  
The Many ◽  
Clinical Conditions ◽  
Relationship Of ◽  
The Relationship ◽  
Clinical Problems ◽  
Insight Into

Rett syndrome (RTT, MIM#312750) is a neurodevelopmental disorder that is classified as an autism spectrum disorder. Clinically, RTT is characterized by psychomotor regression with loss of volitional hand use and spoken language, the development of repetitive hand stereotypies, and gait impairment. The majority of people with RTT have mutations in Methyl-CpG-binding Protein 2 (MECP2), a transcriptional regulator. Interestingly, alterations in the function of the protein product produced by MECP2, MeCP2, have been identified in a number of other clinical conditions. The many clinical features found in RTT and the various clinical problems that result from alteration in MeCP2 function have led to the belief that understanding RTT will provide insight into a number of other neurological disorders. Excitingly, RTT is reversible in a mouse model, providing inspiration and hope that such a goal may be achieved for RTT and potentially for many neurodevelopmental disorders.

Is schizophrenia an HLA-associated disease?

1979 ◽  
Vol 9 (4) ◽  
pp. 721-728 ◽  
Author(s):  
Peter McGuffin
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Postsynaptic Membrane ◽  
Leukocyte Antigen ◽  
Hla System ◽  
Central Neurotransmitters ◽  
Disease Subtypes ◽  
The Relationship

SYNOPSISCertain specificities of the human leukocyte antigen (HLA) system have been shown to be associated with particular diseases. A review of recent studies in schizophrenia shows inconsistent results for schizophrenia as a whole, although a significant increase in HLA A28 remains on combining the data. There are more consistent findings for disease subtypes. In particular, HLA A9 and HLA CW4 are increased in paranoid schizophrenics, while HLA Al and the A1–B8 haplotype are increased in nuclear forms. It is postulated that the relationship between the schizophrenias and certain HLA types could be due to an influence of the latter upon neuronal postsynaptic membrane sensitivity to central neurotransmitters such as dopamine.

scholarly journals Influence of a low-dose tacrolimus protocol on the appearance of de novo donor-specific antibodies during 7-years of follow-up after renal transplantation

2020 ◽  
Author(s):  
Kohei Unagami ◽  
Hideki Ishida ◽  
Miyuki Furusawa ◽  
Kumiko Kitajima ◽  
Toshihito Hirai ◽  
...  
Keyword(s):  
De Novo ◽  
Trough Level ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Serum Trough ◽  
Donor Specific Antibodies ◽  
Allograft Outcome ◽  
The Relationship

Abstract Background Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs). Methods A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not. Results We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P &lt; 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P &lt; 0.001) and showed poor allograft outcome. Conclusions There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4–6 ng/mL during the immunosuppression maintenance period.

scholarly journals HLA-A, -B, -C, -DRB1, and -DQB1 Allele Lineages and Haplotype Frequencies among Saudis

2014 ◽  
Vol 6 ◽  
pp. III.S16769
Author(s):  
Awad E. Osman ◽  
Faviel F. Gonzalez-Galarza ◽  
Mohamed Mubasher ◽  
Hanan Al-Harthi ◽  
Nezar Eltayeb Elsheikh ◽  
...  
Keyword(s):  
Principal Component ◽  
Human Leukocyte ◽  
Marrow Transplant ◽  
Genetic Distances ◽  
Specific Oligonucleotide Probe ◽  
Haplotype Frequencies ◽  
Medical City ◽  
Reported Data ◽  
Sequence Specific Oligonucleotide Probe ◽  
Dqb1 Allele

There are few reported studies on Saudi population for human leukocyte antigens (HLA) genes. We investigated allele lineages (two-digit) and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 loci in 499 healthy unrelated individuals, selected from potential bone marrow transplant (BMT) families’ donors at King Fahad Medical City (KFMC), Saudi Arabia (SA). Genotyping was performed by Sequence Specific Oligonucleotide Probe (SSOP) utilizing a Luminex-based method. Allele lineages and haplotype frequencies were evaluated along with principal component analysis (PCA) to compare findings with previously reported data on Arab related populations. A total of 18 allele lineages for HLA-A, 28 for -B, 14 for -C, 13 for -DRB1, and 5 for -DQB1 were detected. High values for linkage disequilibrium indicators were found for B:C ( D’ = 0.86599) and DRB1:DQB1 ( D’ = 0.89468) loci. Additionally, PCA results confirmed previous findings on this population, but also indicated some genetic distances from other Arab related populations. The present study helps in further investigations of this population in anthropological analysis and HLA-associated disease studies.

Lymphocyte subsets and adhesion molecules expression in heatstroke and heat stress

1998 ◽  
Vol 84 (5) ◽  
pp. 1615-1621 ◽  
Author(s):  
Muhammad M. Hammami ◽  
Abderrezak Bouchama ◽  
Essam Shail ◽  
Hassan Y. Aboul-Enein ◽  
Sultan Al-Sedairy
Keyword(s):  
Heat Stress ◽  
Lymphocyte Subsets ◽  
Human Leukocyte ◽  
T Helper ◽  
Leukocyte Antigen ◽  
Wide Range ◽  
Before And After ◽  
Circulating Lymphocytes ◽  
The Relationship ◽  
Catecholamine Levels

We examined the specificity of the recently reported alterations in circulating lymphocytes in heatstroke by determining lymphocyte subsets in 14 consecutive heatstroke patients before and after cooling and in 7 heat-stressed controls using single- or two-color immunofluorescence flow cytometry. The relationship with catecholamine levels was also studied. In heatstroke, percentages of T (CD3+/CD19−), T-helper (CD4+/CD8−), T-inactive [CD3+/human leukocyte antigen-DR−], CD11a+, CD11c+, and CD44+lymphocytes were significantly decreased, whereas percentages of T-suppressor-cytotoxic (CD8+/CD4−), natural killer (NK; CD3−/CD16+or CD56+), CD3+/CD16+or CD56+, and CD54+lymphocytes were significantly increased, compared with 11 normal controls. The changes in the absolute numbers of lymphocyte subsets were in the same direction and were significant for T-helper, T-suppressor-cytotoxic, NK, CD3+/CD16+or CD56+, and CD11c+lymphocytes. Milder but significant changes in percentages of T-helper, T-suppressor-cytotoxic, CD11c+, and CD44+lymphocytes were seen in heat stress. Cooling was associated with partial or complete normalization, further derangement (CD11a+, CD11c+), or overcorrection (NK, T-suppressor-cytotoxic, CD11b+) of abnormal percentages of lymphocyte subsets. Norepinephrine levels were significantly elevated in heatstroke (4.7-fold) and heat stress (3.2-fold), but did not significantly correlate with lymphocyte subsets. We conclude that heatstroke is associated with significant changes in percentages and in absolute numbers of a wide range of circulating lymphocyte subsets that are not related to elevated catecholamine levels or totally normalized by cooling. Similar, albeit milder, changes are seen in heat stress, suggesting that the two syndromes represent a continuum.

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