Displaying publications 1 - 20 of 59 in total

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  1. Sen P, R N, Houshmand N, Moghadam Kia S, Joshi M, Saha S, et al.
    Rheumatology (Oxford), 2023 Oct 03;62(10):3291-3301.
    PMID: 36734536 DOI: 10.1093/rheumatology/kead057
    OBJECTIVE: COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.

    METHODS: The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups.

    RESULTS: We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P 

    Matched MeSH terms: Autoimmune Diseases*
  2. Abdullah S, Fadzli F, Ramli N, Tan CT
    Mult Scler Relat Disord, 2017 Feb;12:34-38.
    PMID: 28283103 DOI: 10.1016/j.msard.2016.12.011
    BACKGROUND AND OBJECTIVE: The recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs.

    METHOD: MRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS.

    RESULTS: Thirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005). None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group.

    CONCLUSION: There was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference.

    Matched MeSH terms: Demyelinating Autoimmune Diseases, CNS/blood*
  3. Viswanathan S, Hiew FL
    J Clin Apher, 2019 Aug;34(4):434-444.
    PMID: 30829434 DOI: 10.1002/jca.21696
    There has been an increase in the use of therapeutic plasma exchange (TPE) in immune-mediated neurological disorders in recent years. However, accessibility and availability of TPE remains low and costly, especially for a country with limited healthcare funding like Malaysia. With expanding clinical indications in neurological disorders, and increasingly expensive conventional immunomodulatory treatment such as intravenous immunoglobulin and monoclonal antibodies, TPE remains an effective part of first or second-line treatment. In this article, we detailed the historical aspects of the use of TPE in neurological disorders in Malaysia over the last four decades and discussed the challenges behind the establishment of the first in-house neurology-driven TPE service in the country. Local TPE database from a national neurology centre in Kuala Lumpur over the past 20 years was analyzed. We observed a remarkable three folds increase in the use of TPE at our center over the past 10 years (total 131 TPE treatments) compared to a decade prior, with expanding clinical indications predominantly for central nervous system demyelinating disorders. Besides using membrane filtration method, centrifugal technique was adopted, providing new opportunities for other clinical beneficiaries such as a neurologist driven "in-house TPE unit". However, there were real world challenges, especially having to provide services with limited funding, human resources, and space. In addition, much has to be done to improve accessibility, availability, and sustainability of TPE services at our center and nationwide. Nevertheless, even with limited resources and support, it is possible with concerted efforts to work within the confines of these limitations to establish a safe, successful, and sustainable TPE service.
    Matched MeSH terms: Autoimmune Diseases of the Nervous System/therapy
  4. Panirselvam RR, Ramly SS, Harun NA
    MyJurnal
    Systemic lupus erythematosus (SLE) is a debilitating and chronic autoimmune disease which strikes insidiously. The disease currently has a prevalence of 43/ 100 000 individuals in Malaysia. The presentation of the disease is varied resulting in delay in diagnosis and onset of complications prior to management. The disease commonly presents as joint pain and cutaneous manifestations. Neuropsychiatric presentation accounts for 24% of symptoms during onset of illness. This case report highlights that we encountered a patient who presented with neuropsychiatric manifestations, whereby the patient was managed for the psychiatric symptoms prior to the organic diagnosis being made.
    Matched MeSH terms: Autoimmune Diseases
  5. Latiff AH, Kerr MA
    Ann. Clin. Biochem., 2007 Mar;44(Pt 2):131-9.
    PMID: 17362578 DOI: 10.1258/000456307780117993
    IgA deficiency is the most common primary immunoglobulin deficiency. The prevalence in Caucasians is around one in 500, whereas in some Asian populations it is very uncommon. Most individuals with IgA deficiency are clinically asymptomatic. Those with symptoms of immunodeficiency have predominantly sinopulmonary or gastrointestinal infections, which are more severe when associated with IgG2, IgG4 or specific antibody deficiency. IgA deficiency is believed to be one end of a spectrum of immunodeficiency with common variable immunodeficiency at the most severe end. Although primary IgA deficiency is the most commonly encountered form, secondary deficiencies due to drugs or viral infections are recognized. IgA deficiencies can be partial or transient. Primary IgA deficiency is caused by a defect of terminal lymphocyte differentiation, which leads to underproduction of serum and mucosal IgA; affected individuals have normal IgA genes. A number of non-immunoglobulin genes have been implicated in IgA deficiency. There have been many diseases reported in association with IgA deficiency, particularly autoimmune diseases. The most common association is with coeliac disease (CD), which has special significance since CD is usually diagnosed by detection of specific IgA antibodies that are obviously lacking in IgA deficiency. There is no specific treatment for patients with symptomatic IgA deficiency. Antibiotics are prescribed in those with acute infections. A significant proportion of IgA-deficient individuals are reported to have anti-IgA antibodies in their serum. Although blood or blood products given to IgA-deficient individuals can lead to severe, even fatal, transfusion reactions, such reactions are rare.
    Matched MeSH terms: Autoimmune Diseases/immunology; Autoimmune Diseases/metabolism
  6. Bello RO, Chin VK, Abd Rachman Isnadi MF, Abd Majid R, Atmadini Abdullah M, Lee TY, et al.
    Int J Mol Sci, 2018 Apr 11;19(4).
    PMID: 29641433 DOI: 10.3390/ijms19041149
    The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.
    Matched MeSH terms: Autoimmune Diseases/etiology*
  7. Ahmad S, Al-Hatamleh MAI, Mohamud R
    Cell Immunol, 2021 10;368:104412.
    PMID: 34340162 DOI: 10.1016/j.cellimm.2021.104412
    Autoimmunity is the assault of immune response towards self-antigens, resulting to inflammation and tissue injury. It is staged into three phases and caused by malfunction of immune tolerance. In our body, immune tolerance is synchronized by several immunosuppressor cells such as regulatory T cells and B cells as well as myeloid-derived suppressor cells, which are prominently dysregulated in autoimmunity. Hence, targeting these cell populations serve as a significant potential in the therapy of autoimmunity. Nanotechnology with its advantageous properties is shown to be a remarkable tool as drug delivery system in this field. This review focused on the development of therapeutics in autoimmune diseases utilizing various nanoparticles formulation based on two targeting approaches in autoimmunity, passive and active targeting. Lastly, this review outlined the approved present nanomedicines as well as in clinical evaluations and issues regarding the lack of translation of these nanomedicines into the market, despite the abundant of positive experimental observations.
    Matched MeSH terms: Autoimmune Diseases/immunology*
  8. Okuda K, Fu HY, Matsuzaki T, Araki R, Tsuchida S, Thanikachalam PV, et al.
    PLoS One, 2016;11(8):e0160944.
    PMID: 27501378 DOI: 10.1371/journal.pone.0160944
    Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.
    Matched MeSH terms: Autoimmune Diseases/drug therapy*; Autoimmune Diseases/metabolism
  9. Ishak SH, Yaacob LH, Ishak A
    Malays Fam Physician, 2020;15(1):47-49.
    PMID: 32284805
    Dengue is known to cause high morbidity and mortality worldwide. In recent years, there have been increasing cases of dengue fever associated with a rare complication: hemophagocytic syndrome (HPS), which is a dangerous disorder that carries high mortality. It is associated with infections, autoimmune disorders, and malignancies. Prolonged duration of fever and cytopenia together with multi-organ dysfunction out of proportion to the plasma leakage phase should alert clinicians to consider this condition. In this case study, we highlight a 45-year-old woman with underlying diabetes who was admitted due to dengue fever with warning signs. Her conditions deteriorated quickly: she had spontaneous bleeding, evidence of plasma leakage, severe hepatitis, and coagulopathy on the 11th day of illness. With the support of other blood results, such as raised serum ferritin and lactate dehydrogenase, she was diagnosed with severe dengue with hemophagocytosis syndrome. She responded well to intravenous dexamethasone and recovered on the 19th day of illness.
    Matched MeSH terms: Autoimmune Diseases
  10. Singh KK, Wan-Nurfahizul-Izzati W, Ismail A
    Gut Pathog, 2010;2(1):9.
    PMID: 20727206 DOI: 10.1186/1757-4749-2-9
    Neopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.
    Matched MeSH terms: Autoimmune Diseases
  11. Miptah HN, Badlishah Sham SF, Lloyd S, Ramli AS
    MyJurnal
    Septic arthritis is uncommon in immunocompetent young adults. It typically presents in individuals with underlying risk factors. Isolation of Group A Streptococcus (GAS) as the causative agent of septic arthritis is usually associated with autoimmune diseases, chronic skin infections or trauma. Here we report a case of a young lady who is immunocompetent without any prior history of trauma, who presented with an abrupt onset of left knee pain and swelling to the emergency department. An initial diagnosis of acute gout was made and she was treated with non-steroidal anti-inflammatory drug (NSAID). She presented again two days later to a primary care clinic with worsening knee pain and severe left calf pain. A clinical diagnosis of septic arthritis was suspected and the patient was urgently referred to the Orthopaedic team. Synovial fluid from the knee joint aspiration showed growth of GAS. A diagnosis of necrotizing fasciitis was also made as the culture taken from the left calf during incision and drainage (I&D) procedure showed a mixed growth. She eventually underwent surgical debridement twice, together with the administration of several courses of intravenous antibiotics leading to her full recovery after 45 days. This case demonstrates the challenge in making a prompt diagnosis of septic arthritis and probable Type II necrotizing fasciitis in an immunocompetent adult without underlying risk factors. Any delay in diagnosis and treatment would have increased the risk of damage to her knee joint and this may be fatal even in a previously healthy young adult.
    Matched MeSH terms: Autoimmune Diseases
  12. Ch’ng CC, Wong SM, Tan CT
    Neurology Asia, 2016;21(3):261-264.
    MyJurnal
    Background & Objective: Symptomatic sarcocystosis has been said to be rare until recent years, when there were reports of outbreaks of febrile myositis for travellers returning from the Malaysian island resorts. In 2012, an outbreak of Sarcocystis nesbitti infection involving 92 college students and staff occurred after returning from Pangkor Island, Malaysia. A few months after recovering from the febrile illness, some patients complained of hair loss. This study aimed to determine the prevalence, clinical features and outcome of this disorder.
    Methods: All patients who became sick in the outbreak were asked whether they had the hair loss. For those who had, they were interviewed with standard questionnaires, examined and investigated. Patients were followed-up via an online survey 2 years later.
    Results: Out of 89 patients who were ill, 19 patients (21.4%) complained of alopecia. The mean peak onset was 4 months after the initial illness. Eleven patients (57.9%) reported the hair fall of more than 100 per day. The other symptoms were itch 10 (52.6%), scaling 10 (52.6%), erythema 4 (21.1%), none had scarring. Eleven patients (57.8%) had positive antinuclear factor with high titre (speckled or nucleolar pattern). Two years after the event, 10 had complete or near complete spontaneous recovery, 1 had partial response and 1 had no improvement.
    Conclusions: A delayed transient diffuse alopecia is seen in close to half of patients with Sarcocystis nesbittiinfection. This high frequency of positive ANF suggested an immune-mediated mechanism.

    Study site: Dermatology Clinic, Universiti Malaya Medical Centre (UMMC)
    Matched MeSH terms: Autoimmune Diseases
  13. Das B
    Biomed Imaging Interv J, 2007 Oct;3(4):e45.
    PMID: 21614297 DOI: 10.2349/biij.3.4.e45
    Radiosynovectomy is a novel method of treatment for several acute and chronic inflammatory joint disorders. A small amount of a beta-emitting radionuclide is injected into the affected joint delivering a radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is destroyed, secretion of fluid and accumulation of inflammation causing cellular compounds stops and the joint surfaces become fibrosed, providing long term symptom relief. The radionuclides are injected in colloidal form so that they remain in the synovium and are not transported by lymphatic vessels causing radiation exposure to other organs. Complete reduction of knee joint swelling has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow, shoulder, ankle and hip joints showed significant improvement in 50-60% and restoration of normal function and long term pain relief has been achieved in about 70% of small finger joints. In hemophilic arthropathies complete cessation of bleeding in about 60% and improved mobility in 75% of patients has been reported.

    Matched MeSH terms: Autoimmune Diseases
  14. Zanna MY, Yasmin AR, Omar AR, Arshad SS, Mariatulqabtiah AR, Nur-Fazila SH, et al.
    Int J Mol Sci, 2021 Jul 28;22(15).
    PMID: 34360810 DOI: 10.3390/ijms22158044
    Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most efficient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this review has elucidated the general aspects of DCs as well as the current dynamic perspectives and distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, cat, horse, cattle, sheep, pig, and non-human primates. Besides the role that DCs play in immune response, they also play a pathogenic role in many diseases, thus becoming a target in disease prevention and treatment. In addition, its roles in clinical immunology have also been addressed, which include its involvement in transplantation, autoimmune disease, viral infections, cancer, and as a vaccine target. Therefore, based on the current knowledge and understanding of the important roles they play, DCs can be used in the future as a powerful tool for manipulating the immune system.
    Matched MeSH terms: Autoimmune Diseases/immunology
  15. McShane CM, Murray LJ, Landgren O, O'Rorke MA, Korde N, Kunzmann AT, et al.
    Cancer Epidemiol Biomarkers Prev, 2014 Feb;23(2):332-42.
    PMID: 24451437 DOI: 10.1158/1055-9965.EPI-13-0695
    BACKGROUND: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma.

    METHODS: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011.

    RESULTS: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. "Any autoimmune disorder" was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80).

    CONCLUSIONS: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin.

    IMPACT: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma.

    Matched MeSH terms: Autoimmune Diseases/immunology*; Autoimmune Diseases/epidemiology
  16. Lee YH, Lew PH, Cheah CW, Rahman MT, Baharuddin NA, Vaithilingam RD
    J Int Acad Periodontol, 2019 07 01;21(3):99-110.
    PMID: 31473702
    Periodontitis (PD), a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss, is a major oral health problem. Rheumatoid arthritis (RA), with a global prevalence of 1%, is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of cartilage and bone. Studies have reported an association between PD and RA whereby PD is reportedly more severe in patients with established RA. Justification for the plausible link between both conditions is based on shared characteristics and pathogenic similarities with regard to risk factors, immunogenetics and tissue destruction pathways. The search for the possible mechanism linking PD to RA continues as it can play an important role in enabling early intervention in the form of prevention and treatment of infection. This will ultimately improve patients' oral health related quality of life and reduce societal burden related to increased patient discomfort and treatment costs. The current review provides an update on the cellular and molecular events that have thus far explained the link.
    Matched MeSH terms: Autoimmune Diseases*
  17. Lim TT
    Parkinsonism Relat Disord, 2017 Nov;44:106-109.
    PMID: 29097081 DOI: 10.1016/j.parkreldis.2017.08.017
    PURPOSE OF REVIEW: To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders.

    RECENT FINDINGS: The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome.

    SUMMARY: Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy.

    Matched MeSH terms: Autoimmune Diseases*
  18. Mohamed SIA, Jantan I, Haque MA
    Int Immunopharmacol, 2017 Sep;50:291-304.
    PMID: 28734166 DOI: 10.1016/j.intimp.2017.07.010
    Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.
    Matched MeSH terms: Autoimmune Diseases
  19. Kozielewicz P, Alomar H, Yusof S, Grafton G, Cooper AJ, Curnow SJ, et al.
    FEBS Open Bio, 2017 12;7(12):1982-1993.
    PMID: 29226084 DOI: 10.1002/2211-5463.12339
    A number of members of the G protein-coupled receptor class of cell surface receptors are 'orphans' with no known endogenous ligand. One of these orphan receptors is GPR61; there are little data about its expression in human cells and tissues. In this study, we investigated the post-translational modification of GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12) and the impact of this modification upon the subcellular expression of the protein. The N-glycosylation inhibitor tunicamycin reduced the apparent molecular weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant with disrupted consensus N-glycosylation site. Analysis of GPR61 expression demonstrated that tunicamycin treatment reduced considerably heterologous expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being readily expressed at the cell surface. These results demonstrate that GPR61 is subject to N-glycosylation but suggest this is not a prerequisite for cell surface expression, although N-glycosylation of other proteins may be important for cell membrane expression of GPR61. Expression of GPR61 protein was demonstrated at the cellular level in human hippocampus and human peripheral blood mononuclear cells. In the latter, there was a significantly higher expression of GPR61 in the Th17 cell subset in comparison with resting CD4+ cells, which may point toward a potential role for the GPR61 receptor in autoimmune diseases. This is the first report that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus. These findings will help guide studies to investigate the function of GPR61.
    Matched MeSH terms: Autoimmune Diseases
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