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Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20–30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08–7.035), C*03:04 (OR = 3.665, 95%CI: 2.102–6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326–3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation (KT) is the best therapy in children with end‐stage renal disease (ESRD), however, improving long‐term graft survival remains challenging. The aim of this study was to determine graft survival and potential risk factors in pediatric patients who undergo deceased donor KT with a steroid‐based regimen. Methods: The medical records of children who underwent their first deceased donor KT in Srinagarind Hospital (Khon Kaen, Thailand) between 2001 and 2020 were reviewed. Results: Seventy‐two patients were studied. Male adolescents were the predominant recipients and the majority of donors were young adult males. Non‐glomerular disease, particularly hypoplastic/dysplastic kidney disease, was the major cause of ESRD (48.61%). The mean cold ischemic time (CIT) was 18.29 ± 5.29 h. Most of the recipients had more than 4 human leukocyte antigen (HLA) mismatched loci with positive HLA‐DR mismatch (52.78%). Induction therapy was administered in 76.74% of recipients. Tacrolimus plus mycophenolate sodium and prednisolone was the most common immunosuppressive maintenance regimen (69.44%). Graft failure occurred in 18 patients, mostly due to graft rejection (50%). Graft survival at 1, 3, and 5 years after KT were 94.40%, 86.25%, and 74.92%, respectively. The only significant risk factor of graft failure in this study was delayed graft function (DGF) (adjusted HR = 3.55; 95%CI: 1.14, 11.12; p =.029). Patient survival at 1, 3, and 5 years was 100%, 98.48%, and 96.19%, respectively. Conclusion: The short‐term outcomes of pediatric KT from deceased donors were satisfactory; however, prevention of DGF would result in better outcomes. [ABSTRACT FROM AUTHOR]

Kidney disease, as a global health problem, can progress to kidney failure. Kidney transplantation is a treatment option for end-stage disease and an alternative to dialysis. Complement-dependent cytotoxicity tests and flow cytometry are methods used to test for compatibility between autoantibodies and donor recipient. Antibodies against donor human leukocyte antigens (HLAs), linked to hyperacute or severely acute rejection, frequently result in graft loss. Currently, fluorescent bead assay (Luminex®) technology is used in Thailand for HLA-antibody typing tests. However, each test requires specific location and time, expensive equipment, and high costs. The goal of such research is that, HLA-antibody typing tests can be performed wherever it is the most convenient for recipients and hospitals. A further advantage is that the surgeon can perform a final test for confirmation before the surgery. Numerous technologies are currently available for this purpose. The focus of this study was on the Fe3O4 magnetic nanoparticles (MNPs) immobilized with HLAs frequently found in the Thai population. These were examined using nuclear magnetic resonance (NMR) to measure HLA antibody typing. MNPs have recently attracted considerable attention because of their strong magnetization and large surface areas. Immobilization reactions with antigens and the straightforward magnetic separation of MNPs are low-cost techniques. Hence, the commercialization of Fe3O4 MNPs is favorable. In this study, MNPs were functionalized with 3-aminopropyl triethoxysilane (APTES) in toluene and ethanol, and the nanoparticles were streptavidin activated after APTES treatment. A specific biotinylated HLA for the Thai population was used and immobilized on streptavidin. The MNPs were effectively immobilized. The magnetic properties can be modified by adding other ions to Fe3O4. We discovered that the shape and size variations of Fe3O4 MNPs may have an impact on the amount of functionalized and immobilized surface area. [ABSTRACT FROM AUTHOR]

The recombinant, live, attenuated, tetravalent dengue vaccine CYD-TDV has shown efficacy against all four dengue serotypes. In this exploratory study (CYD59, NCT02827162), we evaluated potential associations of host human leukocyte antigen (HLA) alleles with dengue antibody responses, CYD-TDV vaccine efficacy, and virologically-confirmed dengue (VCD) cases. Children 4–11 years old, who previously completed a phase 2b efficacy study of CYD-TDV in a single center in Thailand, were included in the study. Genotyping of HLA class I and II loci was performed by next-generation sequencing from DNA obtained from 335 saliva samples. Dengue neutralizing antibody titers (NAb) were assessed as a correlate of risk and protection. Regression analyses were used to assess associations between HLA alleles and NAb responses, vaccine efficacy, and dengue outcomes. Month 13 NAb log geometric mean titers (GMTs) were associated with decreased risk of VCD. In the vaccine group, HLA-DRB1*11 was significantly associated with higher NAb log GMT levels (beta: 0.76; p = 0.002, q = 0.13). Additionally, in the absence of vaccination, HLA associations were observed between the presence of DPB1*03:01 and increased NAb log GMT levels (beta: 1.24; p = 0.005, q = 0.17), and between DPB1*05:01 and reduced NAb log GMT levels (beta: −1.1; p = 0.001, q = 0.07). This study suggests associations of HLA alleles with NAb titers in the context of dengue outcomes. This study was registered with clinicaltrials.gov: NCT02827162. [ABSTRACT FROM AUTHOR]

Background: Recently, the authors had reported a case with abacavir hypersensitivity reaction (ABC-HSR), the first diagnosed patient at the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC). There was no data regarding the incidence or prevalence of ABC-HSR previously reported in Thailand. Objective: To study the prevalence of ABC-HSR, the abacavir use pattern and the cost effectiveness for the routine human leukocyte antigen (HLA)-B*5701 screening before abacavir use by analyses of the MSMC data. Materials and Methods: All patients at the MSMC who were prescribed abacavir from October 1, 2010 to September 30, 2020 were retrospectively reviewed for ABC-HSR and the abacavir use pattern at the time when abacavir was started. The cost-effectiveness analysis was applied by analyzing the cost between the routine HLA-B*5701 screening before abacavir use and the HLA-B*5701 confirmation for ABC-HSR. The cost for the prevention of a case of ABC-HSR was defined. Results: There were total of 54 patients who were prescribed abacavir and only one ABC-HSR case diagnosed. The prevalence of ABC-HSR was 1.85%. The main reason for the abacavir prescription was a substitution for tenofovir (TDF) because of the TDF adverse effects (81.13%). The HLA-B*5701 screening before abacavir use was done in 26.42% at the MSMC. If all eligible patients were routinely screened for the HLA-B*5701 allele before abacavir use, the cost would be 54,000 Baht. The cost for the diagnosis and the management of the ABC-HSR case was 7,230 Baht. The cost for the prevention of a case of ABC-HSR was 46,770 Baht. Conclusion: The prevalence of ABC-HSR was low. The main reason for abacavir use was a substitution for TDF. The cost for the prevention for a case of ABC-HSR was 46,770 Baht which would be less if the cost for the HLA-B*5701 test was reduced. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives. [ABSTRACT FROM AUTHOR]