Displaying publications 21 - 36 of 36 in total

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  1. Different serotypes of dengue viruses differently regulate the expression of the host cell antigen processing machinery
    Gan CS, Yusof R, Othman S
    Acta Trop, 2015 Sep;149:8-14.
    PMID: 25981524 DOI: 10.1016/j.actatropica.2015.05.005
    Dengue virus (DV) infection demonstrates an intriguing virus-induced intracellular membrane alteration that results in the augmentation of major histocompatibility complex (MHC) class I-restricted antigen presentation. As oppose to its biological function in attracting CD8(+) T-cells, this phenomenon appears to facilitate the immune evasion. However, the molecular events that attribute to the dysregulation of the antigen presenting mechanism (APM) by DV remain obscure. In this study, we aimed to characterize the host cell APM upon infection with all serotypes of whole DV. Cellular RNA were isolated from infected cells and the gene expressions of LMP2, LMP7, TAP1, TAP2, TAPBP, CALR, CANX, PDIA3, HLA-A and HLA-B were analyzed via quantitative PCR. The profiles of the gene expression were further validated. We showed that all four DV serotypes modulate host APM at the proteasomal level with DV2 showing the most prominent expression profile.
    Matched MeSH terms: Histocompatibility Antigens Class I/genetics*; Histocompatibility Antigens Class I/immunology
  2. The search for a matched bone marrow donor in the Malaysian population
    Chan, L.L., Law, C.W., Hunn, P.S., Yew, C.B., Lim, P.P.L., Teo, L.T., et al.
    Malaysian Journal of Child Health, 1997;9(2):182-188.
    MyJurnal
    In Malaysia, an estimated 50 children per annum suffering from a variety of haematological and inherited disorders would benefit from bone marrow or stem cell trans-plantation. By mendelian inheritance 25% of these children would be able to find a sibling who is a matched histocompatible donor. For the remaining 75% to have a chance at survival, search from another source would have to be made. This could mean a mismatched non-sibling related donor or a matched unrelated donor. We studied the chance of a Malaysian patient finding a matched sibling donor and a matched unrelated donor. Human Leucocyte Antigen (HLA) data from patients and their siblings were analysed. The HLA data were matched against the largest Asian bone marrow donor registry in Taiwan. 95% of the 138,744 donors in this registry come from Taiwanese Hokkien ancestry.
    Matched MeSH terms: Histocompatibility Antigens Class II
  3. Prevalence and risk factors of antibodies towards HLA Class I and Class II in Malaysian renal transplant candidates
    Khairul-Fahmy N, Ismail J, Koay BT, Md-Zakariah MZ, Mansor S, Zulkifli N, et al.
    BMC Nephrol, 2023 Feb 24;24(1):42.
    PMID: 36829106 DOI: 10.1186/s12882-023-03085-6
    Antibody-mediated rejection (AMR) still persists as the major hurdle towards successful renal allograft survival. This paper aims to report on the HLA antibody landscape of renal transplant candidates in Malaysia. A total of 2,219 adult samples from 2016 to 2019 were analysed for anti-HLA antibodies using solid-phase assay. Our findings highlight the prevalence and risk factors for antibodies against HLA antigens in renal transplant settings, which could be beneficial for selecting compatible recipients from deceased organ donors. To the best of our knowledge, this study is the first to demonstrate that ethnic Malay and Chinese showed significantly higher prevalence of anti-HLA antibodies. Based on our multivariate analysis: (i) female gender was associated with higher risk for panel reactive antibodies (PRAs) against Class I, Class II, and Class I and II (p 
    Matched MeSH terms: Histocompatibility Antigens Class I
  4. Effects of macrophage colony-stimulating factor on microglial responses to lipopolysaccharide and beta amyloid
    Vidyadaran S, Ooi YY, Subramaiam H, Badiei A, Abdullah M, Ramasamy R, et al.
    Cell Immunol, 2009;259(1):105-10.
    PMID: 19577228 DOI: 10.1016/j.cellimm.2009.06.005
    A challenge for studies involving microglia cultures is obtaining sufficient cells for downstream experiments. Macrophage colony-stimulating factor (M-CSF) has been used to improve yield of microglia in culture. However, the effects of M-CSF on activation profiles of microglia cultures are still unclear. Microglia activation is characterised by upregulation of co-stimulatory molecules and an inflammatory phenotype. The aim of this study is to demonstrate whether M-CSF supplementation alters microglial responses in resting and activated conditions. Microglia derived from mixed glia cultures and the BV-2 microglia cell line were cultivated with/without M-CSF and activated with lipopolysaccharide (LPS) and beta amyloid (Abeta). We show M-CSF expands primary microglia without affecting microglial responses to LPS and Abeta, as shown by the comparable expression of MHC class II and CD40 to microglia grown without this growth factor. M-CSF supplementation in BV-2 cells had no effect on nitric oxide (NO) production. Therefore, M-CSF can be considered for improving microglia yield in culture without introducing activation artefacts.
    Matched MeSH terms: Histocompatibility Antigens Class II/metabolism
  5. Fulltext SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression
    Ten LC, Chin YM, Tai MC, Chin EF, Lim YY, Suthandiram S, et al.
    Sci Rep, 2017 01 31;7:41400.
    PMID: 28139690 DOI: 10.1038/srep41400
    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
    Matched MeSH terms: Histocompatibility Antigens Class II/genetics*
  6. Fulltext Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa
    Mohamed M, Gardeitchik T, Balasubramaniam S, Guerrero-Castillo S, Dalloyaux D, van Kraaij S, et al.
    J Inherit Metab Dis, 2020 11;43(6):1382-1391.
    PMID: 32418222 DOI: 10.1002/jimd.12255
    Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P2 were decreased. Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4-kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3 . Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature ageing and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics.
    Matched MeSH terms: Minor Histocompatibility Antigens/genetics*
  7. Expression profile of immune-related genes in Lates calcarifer infected by Cryptocaryon irritans
    Mohd-Shaharuddin N, Mohd-Adnan A, Kua BC, Nathan S
    Fish Shellfish Immunol, 2013 Mar;34(3):762-9.
    PMID: 23296118 DOI: 10.1016/j.fsi.2012.11.052
    Cryptocaryon irritans causes Cyptocaryonosis or white spot disease in a wide range of marine fish including Lates calcarifer (Asian seabass). However, the immune response of this fish to the parasite is still poorly understood. In this study, quantitative polymerase chain reaction (qPCR) was performed to assess the expression profile of immune-related genes in L. calcarifer infected by C. irritans. A total of 21 immune-related genes encoding various functions in the fish immune system were utilized for the qPCR analysis. The experiment was initiated with the infection of juvenile fish by exposure to theronts from 200 C. irritans cysts, and non-infected juvenile fish were used as controls. Spleen, liver, gills and kidney tissues were harvested at three days post-infection from control and infected fish. In addition, organs were also harvested on day-10 post-infection from fish that had been allowed to recover from day-4 up to day-10 post-infection. L. calcarifer exhibited pathological changes on day-3 post-infection with the characteristic presence of white spots on the entire fish body, excessive mucus production and formation of a flap over the fish eye. High quality total RNA was extracted from all tissues and qPCR was performed. The qPCR analysis on the cohort of 21 immune-related genes of the various organs harvested on day-3 post-infection demonstrated that most genes were induced significantly (p 
    Matched MeSH terms: Histocompatibility Antigens Class II/genetics; Histocompatibility Antigens Class II/metabolism
  8. Fulltext The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus
    Azizah MR, Ainoi SS, Kuak SH, Kong NCT, Normaznah Y, Rahim MN
    Asian Pac J Allergy Immunol, 2001 Jun;19(2):93-100.
    PMID: 11699726
    The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
    Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Histocompatibility Antigens Class II/genetics; Histocompatibility Antigens Class II/immunology*
  9. In vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumours
    Khairuddin N, Blake SJ, Firdaus F, Steptoe RJ, Behlke MA, Hertzog PJ, et al.
    Immunol Cell Biol, 2014 Feb;92(2):156-63.
    PMID: 24217808 DOI: 10.1038/icb.2013.75
    Small interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-α (IFNα) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNα were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies.
    Matched MeSH terms: Histocompatibility Antigens Class I/immunology
  10. Fulltext Human Leukocyte Antigen (HLA) class I and II datasets for sudanese
    Dafalla AM, Edinur HA, Abdelwahed M, Elemam AA, Ibrahim AA, Mohamadani A, et al.
    Data Brief, 2019 Jun;24:104027.
    PMID: 31193964 DOI: 10.1016/j.dib.2019.104027
    Sudan is located in the heart of Africa and surrounded by eight countries with people of different ethnic origins. Historical records show that the population of the Sudan is a mixture of Arabic, West Asian Arabic and sub-Saharan African elements. The present survey provides data on allele lineages, and haplotype frequencies of Human Leukocyte Antigen (HLA) class I (HLA-A and HLA-B) and class II (HLA-DR and -HLA-DQ) loci in 11 Sudanese populations. The sampled individuals are all local transplant donors who provided informed consent for HLA analyses on their blood samples and were registered at National Cancer Institute, University of Gezira, Wad Medani. The HLA class I and II data reported here can be subjected for future analyses of genetic structure and health in Sudan. These include as reference datasets for identifying the association between HLA and diseases and for designing donor recruitment strategies.
    Matched MeSH terms: Histocompatibility Antigens Class I
  11. Allele HLA-DQB1*06 reduces fibrosis score in patients with non-alcoholic fatty liver disease
    Tan HL, Zain SM, Eng HS, Mohamed Z, Mahadeva S, Chan WK, et al.
    Hepatology research : the official journal of the Japan Society of Hepatology, 2020 May 14.
    PMID: 32410320 DOI: 10.1111/hepr.13525
    AIM: Human leukocyte antigen (HLA) regions were highlighted as important genetic markers for various liver diseases by hepatology-related genome-wide association studies. Replication studies in non-alcoholic fatty liver disease (NAFLD) are limited and none has investigated the association of HLA alleles with non-alcoholic steatohepatitis (NASH) and other histological characteristics. In the current study, we examined the association of HLA-DQA1 and HLA-DQB1 alleles with NAFLD spectrum and its histological characteristics.

    METHODS: Consecutive biopsy-proven NAFLD patients (n = 191) and healthy controls (n = 188) were enrolled and genotyped for HLA-DQA1 and HLA-DQB1 alleles using the sequence-specific oligonucleotide-polymerase chain reaction method.

    RESULTS: No association was found between the HLA alleles and NAFLD or NASH in a case-control setting. Nevertheless, among NAFLD patients, the frequency of HLA-DQB1*06 allele was significantly the lowest in NASH with significant fibrosis (10.4%) and approximately similar for NASH without significant fibrosis (22.9%) and NAFL (22.5%) (P = 0.004). It is noteworthy that the association remains significant after correction for multiple comparisons (Pc  = 0.04). Multivariate analysis revealed that HLA-DQB1*06 allele is also associated with fibrosis score (P = 0.001); the result remains significant after correction for multiple comparisons.

    CONCLUSION: These findings suggest that HLA-DQB1*06 is associated with lower fibrosis score in NAFLD patients.

    Matched MeSH terms: Histocompatibility Antigens Class I
  12. Fulltext Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment
    Loh SW, Ng WL, Yeo KS, Lim YY, Ea CK
    PLoS One, 2014;9(7):e103915.
    PMID: 25079219 DOI: 10.1371/journal.pone.0103915
    H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.
    Matched MeSH terms: Histocompatibility Antigens/metabolism*
  13. Fulltext Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation
    Wen WX, Soo JS, Kwan PY, Hong E, Khang TF, Mariapun S, et al.
    Breast Cancer Res, 2016 05 27;18(1):56.
    PMID: 27233495 DOI: 10.1186/s13058-016-0717-1
    BACKGROUND: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system.

    METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.

    RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values 

    Matched MeSH terms: Minor Histocompatibility Antigens/genetics*
  14. Identification of the amino acids in the Major Histocompatibility Complex class II region of Scottish Blackface sheep that are associated with resistance to nematode infection
    Stear A, Ali AOA, Brujeni GN, Buitkamp J, Donskow-Łysoniewska K, Fairlie-Clarke K, et al.
    Int J Parasitol, 2019 09;49(10):797-804.
    PMID: 31306661 DOI: 10.1016/j.ijpara.2019.05.003
    Lambs with the Major Histocompatibility Complex DRB1*1101 allele have been shown to produce fewer nematode eggs following natural and deliberate infection. These sheep also possess fewer adult Teladorsagia circumcincta than sheep with alternative alleles at the DRB1 locus. However, it is unclear if this allele is responsible for the reduced egg counts or merely acts as a marker for a linked gene. This study defined the MHC haplotypes in a population of naturally infected Scottish Blackface sheep by PCR amplification and sequencing, and examined the associations between MHC haplotypes and faecal egg counts by generalised linear mixed modelling. The DRB1*1101 allele occurred predominately on one haplotype and a comparison of haplotypes indicated that the causal mutation or mutations occurred in or around this locus. Additional comparisons with another resistant haplotype indicated that mutations in or around the DQB2*GU191460 allele were also responsible for resistance to nematode infections. Further analyses identified six amino acid substitutions in the antigen binding site of DRB1*1101 that were significantly associated with reductions in the numbers of adult T. circumcincta.
    Matched MeSH terms: Histocompatibility Antigens Class II/chemistry*
  15. Fulltext Molecular and genomic characterisation of a panel of human anal cancer cell lines
    Guerra GR, Kong JC, Millen RM, Read M, Liu DS, Roth S, et al.
    Cell Death Dis, 2021 Oct 18;12(11):959.
    PMID: 34663790 DOI: 10.1038/s41419-021-04141-5
    Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
    Matched MeSH terms: Histocompatibility Antigens Class I/metabolism
  16. In vitro characterization of chicken bone marrow-derived dendritic cells following infection with very virulent infectious bursal disease virus
    Yasmin AR, Yeap SK, Tan SW, Hair-Bejo M, Fakurazi S, Kaiser P, et al.
    Avian Pathol, 2015;44(6):452-62.
    PMID: 26305169 DOI: 10.1080/03079457.2015.1084997
    Infectious bursal disease is caused by infectious bursal disease virus (IBDV), an immunosuppressive virus that targets immune cells such as B cells and macrophages. However, the involvement of dendritic cells (DCs) during IBDV infection is not well understood. In this study the in vitro effects of live and inactivated very virulent IBDV (vvIBDV) UPM0081 on bone marrow-derived DCs (BM-DC) were characterized and compared with BM-DC treated with lipopolysaccharide (LPS). Morphologically, BM-DC treated with LPS and vvIBDV showed stellate shape when compared to immature BM-DC. In addition, LPS-treated and both live and inactivated vvIBDV-infected BM-DC expressed high levels of double positive CD86 and major histocompatibility complex class II antigens (>20%). vvIBDV-infected BM-DC showed significantly higher numbers of apoptotic cells compared to LPS. Replication of vvIBDV was detected in the infected BM-DC as evidenced by the increased expression of VP3 and VP4 IBDV antigens based on flow cytometry, real-time polymerase chain reaction and immunofluorescence tests. Levels of different immune-related genes such as interleukin-1β (IL-1β), CXCLi2 (IL-8), IL-18, interferon gamma (IFN-γ, IL-12α, CCR7 and Toll-like receptor-3 (TLR3) were measured after LPS and vvIBDV treatments. However, marked differences were noticed in the onset and intensity of the gene expression between these two treatment groups. LPS was far more potent than live and inactivated vvIBDV in inducing the expression of IL-1β, IL-18 and CCR7 while expression of Th1-like cytokines, IFN-γ and IL-12α were significantly increased in the live vvIBDV treatment group. Meanwhile, the expression of TLR3 was increased in live vvIBDV-infected BM-DC as compared to control. Inactivated vvIBDV-treated BM-DC failed to stimulate IFN-γ, IL-12α and TLR3 expressions. This study suggested that BM-DC may serve as another target cells during IBDV infection which require further confirmation via in vivo studies.
    Matched MeSH terms: Histocompatibility Antigens Class II
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