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  1. Castaño-Rodríguez N, Kaakoush NO, Pardo AL, Goh KL, Fock KM, Mitchell HM
    Hum Immunol, 2014 Aug;75(8):808-15.
    PMID: 24929142 DOI: 10.1016/j.humimm.2014.06.001
    Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.
  2. Miyaji K, Shahrizaila N, Umapathi T, Chan YC, Hirata K, Yuki N
    Hum Immunol, 2014 Nov;75(11):1089-91.
    PMID: 25286001 DOI: 10.1016/j.humimm.2014.09.010
    Ezrin, radixin and moesin, which are strongly expressed in the Schwann cell microvilli, are putative targets for autoantibodies in acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP). An association between anti-moesin IgG antibodies and cytomegalovirus-related AIDP has been postulated. None of 41 AIDP patients, including 8 cytomegalovirus-related AIDP patients, and 23 CIDP had IgG or IgM antibodies to ezrin, radixin and moesin; whereas, one patient with cytomegalovirus-related AIDP had anti-ezrin IgM antibodies. Ezrin, radixin and moesin are unlikely targets for autoantibodies in AIDP and CIDP, and the association of anti-moesin antibodies with cytomegalovirus-related AIDP was not confirmed.
  3. Dhaliwal JS, Wong L, Kamaluddin MA, Yin LY, Murad S
    Hum Immunol, 2011 Oct;72(10):889-92.
    PMID: 21762745 DOI: 10.1016/j.humimm.2011.06.013
    The incidence of aplastic anemia is reported to be higher in Asia than elsewhere. We studied the frequency of human leukocyte antigen (HLA) DRB1 alleles in aplastic anemia patients from 2 genetically similar aboriginal groups, the Kadazan and the Dusun, and compared them with genetically matched community and hospital controls. HLA-DRB1*15 was significantly higher in the patients compared with controls (p = 0.005), confirming similar findings in Japanese and Caucasian studies. Further testing indicated a significantly higher frequency of HLA-DRB1*1501 in patients compared with controls (p = 0.0004) but no significant difference in the frequency of HLA-DRB1*1502. The high frequency of HLA-DRB1*15 in the Kadazan and Dusun population combined with the wide variety of environmental factors associated with aplastic anemia could be the reason for the elevated incidence of aplastic anemia in the Kadazan and Dusun in Sabah.
  4. Idris ZM, Miswan N, Muhi J, Mohd TA, Kun JF, Noordin R
    Hum Immunol, 2011 Jul;72(7):607-12.
    PMID: 21513760 DOI: 10.1016/j.humimm.2011.03.017
    Lymphatic filariasis (LF) is a parasitic disease caused by threadlike worms of the Brugia and Wuchereria species that live in the human lymphatic system. Regulatory T cells (Tregs) may play a key role in the pathogenesis of LF, and cytotoxic T-lymphocyte antigen-4 (CTLA4) expressed by Tregs is a potential candidate gene because it modulates T-cell activation. A case-control study was performed to establish a potential association of 5 CTLA4 gene promoter single nucleotide polymorphisms (SNPs; rs733618, rs11571316, rs5742909, rs231775, and rs16840252) with the occurrence of LF in an East Malaysian population (320 LF-infected individuals and 150 healthy controls). Polymorphisms were evaluated using TaqMan real-time polymerase chain reaction followed by direct sequencing. LF carriers of the rs733618 AG genotypes (p = 0.02) and those with combined minor allele G carriers (AG + GG; p = 0.01) exhibited a significantly decreased risk for LF. Among the asymptomatic amicrofilaremic cases, positive associations were reported for all genotypes and variants of rs733618 with odds ratios (ORs) ranging from 0.27 to 0.45. In the asymptomatic microfilaremic cases, marker rs231775 exhibited a significant decreased risk, with ORs ranging from 0.50 to 0.57. The study has identified SNPs in the CTLA4 promoter gene that may be functionally linked with susceptibility to LF.
  5. Edinur HA, Zafarina Z, Spínola H, Nurhaslindawaty AR, Panneerchelvam S, Norazmi MN
    Hum Immunol, 2009 Jul;70(7):518-26.
    PMID: 19364514 DOI: 10.1016/j.humimm.2009.04.003
    In this study, human leukocyte antigen (HLA) class I and II were examined through sequence-specific primer typing in 176 unrelated individuals from six Malay subethnic groups of Peninsular Malaysia: Kelantan (n = 25), Minangkabau (34), Jawa (30), Bugis (31), Banjar (33), and Rawa (23). The most common HLA alleles in all groups were A*24 (26-41%), Cw*07 (24-32%), B*15 (22-30%), DRB1*12 (15-36%), and DQB1*03 (25-51%). The Malay subethnic groups studied demonstrated a close relationship to each other and to other Asian populations, despite specific differences between them. Banjar, Bugis, and Jawa Malays demonstrated no significant difference from each other, which could be a result of their related origin from the islands around the Java Sea. These three Malay subethnic groups were then collapsed into one group, which also helped to increase the sample number and sharpen statistical results. Minangkabau and Rawa Malays exhibited high similarities in allele group and haplotype frequencies, which could be a consequence of their common origin from Sumatera. Kelantan Malays, in addition to their statistically significant differences compared with the other groups, also exhibited differences on the most frequent haplotypes, which are almost absent in the other subethnic groups studied.
  6. Wong RSY
    Hum Immunol, 2015 Oct;76(10):781-8.
    PMID: 26429327 DOI: 10.1016/j.humimm.2015.09.038
    Spondyloarthritis (SpA) is a family of interrelated inflammatory arthritis that includes ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, arthritis related to inflammatory bowel disease and undifferentiated SpA. The classification, epidemiology, pathogenesis and treatment of SpA have been extensively reviewed in the published literature. Reviews on the use of stem cells in various autoimmune diseases in general are also common. However, a review on the role of stem cells in SpA is currently lacking. This review focuses on the involvement of stem cells in the pathogenesis of SpA and the application of different types of stem cells in the treatment of SpA. It also addresses some of the complications which may arise as a result of the use of stem cells in the treatment of SpA.
  7. Tasnim AR, Allia S, Edinur HA, Panneerchelvam S, Zafarina Z, Norazmi MN
    Hum Immunol, 2016 Aug;77(8):618-619.
    PMID: 27296326 DOI: 10.1016/j.humimm.2016.06.009
    The earliest settlers in Peninsular Malaysia are the Orang Asli population, namely Semang, Senoi and Proto Malays. In the present study, we typed the HLA-A, -B and -DRB1 loci of the Kensiu and Semai Orang Asli sub-groups. Sequence-based HLA typing was performed on 59 individuals from two Orang Asli sub-groups. A total of 11, 18 and 14 HLA-A, -B and -DRB1 alleles were identified, respectively. These data are available in the Allele Frequencies Net Database under the population name "Malaysia Kedah Kensiu" and "Malaysia Pahang Semai".
  8. Norhalifah HK, Syafawati WU, Che Mat NF, Chambers GK, Edinur HA
    Hum Immunol, 2016 Apr;77(4):338-9.
    PMID: 26820937 DOI: 10.1016/j.humimm.2016.01.015
    Cytokines are involved in immune responses and the pathogenesis of various diseases. Allelic variations within the genes coding for various ∼30kDa cytokine protein/glycoproteins have been reported for many populations and have been the subjects of many ancestry and health analyses. In this study, we typed 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes of 165 Orang Asli individuals by using sequence specific primer-polymerase chain reaction (SSP-PCR) assay. The volunteers came from all across the Peninsular of Malaysia and belong to six Orang Asli subgroups; Batek, Kensiu, Lanoh, Che Wong, Semai and Orang Kanaq. Here we report our general findings and original genotype data and their associated analyses (Hardy-Weinberg proportions, estimation of allele and haplotype frequencies) can be found in the supplementary files and will be held at Allele Frequency Net Database (AFND).
  9. Too CL, Tan LK, Heselynn H, Nor-Shuhaila S, Eashwary M, Wahinuddin S, et al.
    Hum Immunol, 2019 Nov;80(11):906-907.
    PMID: 31558331 DOI: 10.1016/j.humimm.2019.09.005
    A total of 194 Southeast Asia Chinese from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, the HLA-B, HLA-DRB1 and HLA-DQB1 were in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from HWEP in HLA-A (p 
  10. Jalalonmuhali M, Carroll RP, Tsiopelas E, Clayton P, Coates PT
    Hum Immunol, 2020 Jul;81(7):323-329.
    PMID: 32327243 DOI: 10.1016/j.humimm.2020.04.002
    BACKGROUND: Blood transfusion during the post-operative period of kidney transplantation is common as part of a life-saving procedure, especially in the event of acute blood loss. However, there have been conflicting opinions since the pre-cyclosporine era. The risk of sensitization post-transfusion remains the main limiting factor following transfusion in kidney transplant recipients. Thus, the objective of this study is to assess the development of de novo HLA-DSA, HLA-Ab and allograft rejection post blood transfusion.

    METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.

    RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).

    CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.

  11. Tan LK, Mohd-Farid B, Salsabil S, Heselynn H, Wahinuddin S, Lau IS, et al.
    Hum Immunol, 2016 Oct;77(10):818-819.
    PMID: 27370684 DOI: 10.1016/j.humimm.2016.06.022
    A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), -B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).
  12. Carroll RP, Deayton S, Emery T, Munasinghe W, Tsiopelas E, Fleet A, et al.
    Hum Immunol, 2019 Aug;80(8):573-578.
    PMID: 31014826 DOI: 10.1016/j.humimm.2019.04.005
    High levels of angiotensin receptor antibodies (ATRab) are associated with acute cellular and humoral rejection, vascular occlusion, de novo human leucocyte antigen donor specific antibody (HLA DSA) and poor graft survival in kidney transplant recipients (KTR). Since 2015 we proactively managed patients "at risk" (AR) with ATRab >17 U/ml with perioperative plasma exchange (PLEX) and/or angiotensin receptor blockade (ARB). 44 patients were treated with this protocol. 265 KTR with ATRab ≤17 U/ml deemed "low risk" (LR) were transplanted under standard conditions. PLEX and ARB were not associated with increased risk of: delayed graft function requiring haemodialysis (HDx), hyperkalaemia >5.5 mmol/l requiring HDx, and the combined clinical end-point of severe hypotension, blood transfusion and re-operation for bleeding. Rejection rates were similar at 90 days: 8/44 (18%) in the AR group and 36/265 (14%) in the LR group (p = 0.350). Death censored graft survival was the same between the AR and LR groups with a 94% 48-month graft survival - hazard ratio (log-rank) 1.16 [95% CI 0.2-5.8] p = 0.844. Proactive treatment of ATRab >17 U/ml with PLEX and/or ARB is not associated with increased rates of perioperative complications and comparable rates of rejection and death censored graft survival at 4 years compared to KTR <17 U/ml ATRab.
  13. Ayakannu R, Abdullah NA, Radhakrishnan AK, Lechimi Raj V, Liam CK
    Hum Immunol, 2019 Sep;80(9):755-763.
    PMID: 31054782 DOI: 10.1016/j.humimm.2019.04.018
    Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
  14. Azid NA, Ahmad S, Boer JC, Al-Hatamleh MAI, Mohammad N, Mohd Ashari NS, et al.
    Hum Immunol, 2020 08 06;81(10-11):634-643.
    PMID: 32771274 DOI: 10.1016/j.humimm.2020.07.006
    The interaction of tolerogenic CD103+ dendritic cells (DCs) with regulatory T (Tregs) cells modulates immune responses by inducing immune tolerance. Hence, we determined the proportion of these cells in the peripheral blood mononuclear cells (PBMC) of asthmatic patients. We observed lower trends of CD11b-CD103+ DCs and CD86 within CD11b-CD103+ DCs, while increased levels of Foxp3 expressing CD25+/-TNFR2+ cells in asthmatics. There was a positive correlation in the expression of Foxp3 within CD3+CD4+CD25+TNFR2+ Tregs and CD11b-CD103+ as well as the expression of CD86 within HLA-DR+CD11c+CD11b-CD103+ DCs. In conclusion, we suggest that the increased levels of Tregs in blood could continuously suppress the T helper 2 (Th2) cells activation in the circulation which is also supported by the increase of anti-inflammatory cytokines IL-10 and TNF. Overall, functional immunoregulation of the regulatory cells, particularly Tregs, exhibit immune suppression and induce immune tolerance linked with the immune activation by the antigen presenting cells (APC).
  15. Hoh BP, Umi-Shakina H, Zuraihan Z, Zaiharina MZ, Rafidah-Hanim S, Mahiran M, et al.
    Hum Immunol, 2015 Jun;76(6):421-6.
    PMID: 25858769 DOI: 10.1016/j.humimm.2015.03.019
    Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.
  16. Jalalonmuhali M, Caroll R, Deayton S, Emery T, Humphreys I, Lim SJ, et al.
    Hum Immunol, 2020 Dec;81(12):679-684.
    PMID: 32736900 DOI: 10.1016/j.humimm.2020.07.005
    BACKGROUND: Angiotensin II type 1 receptor antibody (AT1R-Ab) is a non-HLA antibody that has been reported to cause antibody-mediated rejection and graft loss in kidney transplantation. The prevalence of positive AT1R-Ab varies between 8% and 18% in different regions. Thus, this study aims to determine the prevalence of AT1R-Ab among the Malaysian population.

    METHODOLOGY: All sera for AT1R-Ab were collected at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The sera were centrifuged and kept refrigerated at -80 °C before being transported to the South Australian Transplantation and Immunogenetics Laboratory (SATIS). Enzyme-linked immunosorbent assay kit (One Lambda) was used for the detection of AT1R-Ab, and it was performed according to the manufacturer's instructions. The level of >17.1 U/mL was considered to be AT1R-Ab positive; 10.0-17.1 U/mL at risk, and <10.0 U/mL negative.

    RESULTS: A total of 115 samples were collected from 99 patients pre and post-kidney transplant recipients. From the pre-transplant sera (n = 68) 17.7% were positive, 35.3% were at risk and 47.0% were negative. The positive AT1R-Ab cohort were relatively younger, with a mean age of 34.7 ± 8.3 years old and statistically significant, with a p-value of 0.028. Among the sera that were tested positive, 19.0% were from the Chinese ethnicity, 6.7% from Malay and 16.7% from Indian. There was no difference in the rejection episodes, persistent or de novo HLA-DSA, and graft function between the group (AT1R-Ab negative vs AT1R-Ab at risk and positive) and the results were consistent in a model adjusted for all potential confounders.

    CONCLUSION: The prevalence of positive (>17.1 U/mL) pre-transplant AT1R-Ab was 17.7% and 35.3% were at risk (10.0-17.1 U/mL) in our pre-transplant cohort.

  17. Allia S, Norazmi MN, Panneerchelvam S, Zafarina Z
    Hum Immunol, 2019 Jul;80(7):423-424.
    PMID: 30836128 DOI: 10.1016/j.humimm.2019.02.015
    "Bumiputra" or "son of the soil" is a term used to represent the Malays and other indigenous populations of Malaysia. The Malays are Austronesian speaking population and originated from different parts of the Indo-Malay Archipelago. The migration of Malay population from different parts of Indo-Malay Archipelago were mainly due to trading purposes which shaped the current Malay sub-ethnic groups with unique culture and with distinctive dialects. In this study, HLA typing was carried out using Sequence-based Typing (SBT) method on 109 individuals comprising of four Malay sub-ethnic groups namely Kelantan (n = 28), Champa (n = 29), Patani (n = 25) and Mandailing (n = 27) Malays. The HLA data is available in the Allele Frequencies Net Database (AFND).
  18. Nurul-Aain AF, Tan LK, Heselynn H, Nor-Shuhaila S, Eashwary M, Wahinuddin S, et al.
    Hum Immunol, 2020 Jun;81(6):263-264.
    PMID: 32312605 DOI: 10.1016/j.humimm.2020.04.004
    A total of 271 Southeast Asia Indians from Peninsular Malaysia were genotyped for HLA-A, -B, -C, -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, HLA-B and HLA-DQB1 was in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from the HWEP for HLA-A (p 
  19. Jinam TA, Hosomichi K, Nakaoka H, Phipps ME, Saitou N, Inoue I
    Hum Immunol, 2022 Jan;83(1):17-26.
    PMID: 34615609 DOI: 10.1016/j.humimm.2021.09.005
    The heterogenous population of Malaysia includes more than 50 indigenous groups, and characterizing their HLA diversity would not only provide insights to their ancestry, but also on the effects of natural selection on their genome. We utilized hybridization-based sequence capture and short-read sequencing on the HLA region of 172 individuals representing seven indigenous groups in Malaysia (Jehai, Kintaq, Temiar, Mah Meri, Seletar, Temuan, Bidayuh). Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 revealed several ancestry-informative markers. Using SNP-based heterozygosity and pairwise Fst, we observed signals of natural selection, particularly in HLA-A, -C and -DPB1 genes. Consequently, we showed the impact of natural selection on phylogenetic inference using HLA and non-HLA SNPs. We demonstrate the utility of Next Generation Sequencing for generating unambiguous, high-throughput, high-resolution HLA data that adds to our knowledge of HLA diversity and natural selection in indigenous minority groups.
  20. Kevin-Tey WF, Wen WX, Bee PC, Eng HS, Ho KW, Tan SM, et al.
    Hum Immunol, 2023 Mar;84(3):172-185.
    PMID: 36517321 DOI: 10.1016/j.humimm.2022.11.006
    Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation-maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.
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