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Immunology in Malaysia--a review

Bosco J

Ann Acad Med Singap, 1988 Apr;17(2):251-3.
PMID: 3044263

Immunology is a discipline that traverses all branches of clinical medicine. Thus since about ten years ago major hospitals in Malaysia established routine clinical immunology services particularly in the diagnosis of autoimmune/connective tissue disorders. More recently these laboratories have ventured into basic research in Dengue Haemorrhagic Fever, Leukaemia Immunology, Nasopharyngeal Cancer and Leprosy. The rationale for these projects together with early results from them are discussed.

Matched MeSH terms: Autoimmune Diseases/immunology
Autoimmune disease and cancer comorbidity: Current understandings of immune-mediated pathogenesis and treatment

Islam MA, Kamal MA, Gan SH, Alam F

Semin Cancer Biol, 2020 08;64:iii-iv.
PMID: 31589922 DOI: 10.1016/j.semcancer.2019.10.001
Matched MeSH terms: Autoimmune Diseases/immunology
Fulltext Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species

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
Interleukin 23 and autoimmune diseases: current and possible future therapies

Abdo AIK, Tye GJ

Inflamm Res, 2020 May;69(5):463-480.
PMID: 32215665 DOI: 10.1007/s00011-020-01339-9

PURPOSE: IL-23 is a central proinflammatory cytokine with a wide range of influence over immune response. It is implicated in several autoimmune diseases due to the infinite inflammatory loops it can create through the positive feedbacks of both IL-17 and IL-22 arms. This made IL-23 a key target of autoimmune disorders therapy, which indeed was proven to inhibit inflammation and ameliorate diseases. Current autoimmune treatments targeting IL-23 are either by preventing IL-23 ligation to its receptor (IL-23R) via antibodies or inhibiting IL-23 signaling by signaling downstream mediators' inhibitors, with each approach having its own pros and cons.
METHODS: Literature review was done to further understand the biology of IL-23 and current therapies.
RESULTS: In this review, we discuss the biological features of IL-23 and its role in the pathogenesis of autoimmune diseases including psoriasis, rheumatoid arthritis and inflammatory bowel diseases. Advantages, limitations and side effects of each concept will be reviewed, suggesting several advanced IL-23-based bio-techniques to generate new and possible future therapies to overcome current treatments problems.

Matched MeSH terms: Autoimmune Diseases/immunology*
Fulltext Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: a systematic review

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*
The clinical significance of immunoglobulin A deficiency

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
Cyclosporine rescue therapy in autoimmune liver cirrhosis: a case report

Wah-Kheong C, Jaganathan V, Sanjiv M

Turk J Gastroenterol, 2012;23(5):599-603.
PMID: 23161309

Autoimmune hepatitis is an inflammatory condition of the liver that can lead to significant morbidity and mortality. Corticosteroids with or without azathioprine have been shown to improve outcome and are the current standard of care in autoimmune hepatitis patients. However, long-term use of corticosteroids and use of azathioprine could be associated with significant adverse effects that prevent their continued use at optimal dosages or may even require complete cessation. We present a patient with autoimmune liver cirrhosis who was intolerant of corticosteroid and azathioprine, who was successfully treated with cyclosporine. To our knowledge, cyclosporine use has not been reported previously in autoimmune cirrhosis, although it has been used in autoimmune hepatitis patients with reported success and good tolerability. We conclude that cyclosporine seems to be an effective alternative to azathioprine as a steroid-sparing agent in both non-cirrhotic and cirrhotic autoimmune hepatitis.

Matched MeSH terms: Autoimmune Diseases/immunology
Targeting immunosuppressor cells with nanoparticles in autoimmunity: How far have we come to?

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*
Current vision of systemic autoimmune diseases - from diagnosis to management

Islam A, Kamal MA

Endocr Metab Immune Disord Drug Targets, 2018 02 13;18(2):96-97.
PMID: 29508678 DOI: 10.2174/187153031802180213144657
Matched MeSH terms: Autoimmune Diseases/immunology
Immunomodulation by statins: mechanisms and potential impact on autoimmune diseases

Chow SC

Arch Immunol Ther Exp (Warsz), 2009 Jul-Aug;57(4):243-51.
PMID: 19578811 DOI: 10.1007/s00005-009-0038-5

Statins are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and they are the most effective agents for lowering cholesterol in clinical practice for the treatment of cardiovascular diseases. However, it has become clear that statins also have pleiotropic immunomodulatory effects in addition to their lipid-lowering properties. As a result, much attention has been focused on their potential as therapeutic agents for the treatment of inflammatory autoimmune diseases. In this review the effect of statins on the expression and function of a variety of immune-relevant molecules will be discussed alongside the underlying mechanisms that contribute to the immunomodulatory effects of statins.

Matched MeSH terms: Autoimmune Diseases/immunology*
IgG4-related disease: features and treatment response in a multi-ethnic cohort in Singapore

Fong W, Liew I, Tan D, Lim KH, Low A, Leung YY

Clin Exp Rheumatol, 2018 05 24;36 Suppl 112(3):89-93.
PMID: 29846168

OBJECTIVES: To describe the features and treatment outcomes of IgG4-RD in multi-ethnic patients in Singapore.
METHODS: Retrospective study was performed on IgG4-RD patients identified from patient databases in a tertiary hospital.
RESULTS: Fourty-two patients (76% male) were included; 79% fulfilled the 2011 comprehensive diagnostic criteria for IgG4-RD for definite IgG4-RD. 81% were Chinese and 19% were Malays. Common initial manifestations included jaundice (52%), abdominal pain (36%) and swollen salivary glands (26%). Only 36% had a history of allergy. 83% had ≥ 1 organ involvement. Erythrocyte sedimentation rate, immunoglobulin E, IgG2 and IgG4 levels were elevated in 84%, 100%, 70% and 44% of patients, respectively. The most common histopathological feature was >10 IgG4+ cells per high power field (66%). 94% (34/36) of patients were treated with moderate to high doses of glucocorticoids, including 17 patients with combination immunosuppressants. Of these, all patients responded to therapy by 3 months. With a median (range) follow-up of 4.1 (0.4-13.8) years, 69% (25/36) needed low dose of glucocorticoids to maintain disease remission. Twenty-six per cent had relapse of disease, of which 82% had disease recurrence in the same organs.
CONCLUSIONS: Pancreatitis, lymphoadenopathy and cholangitis were the commonest manifestations in Asians with IgG4-RD. All patients responded to glucocorticoid therapy by 3 months, two-thirds required maintenance therapy with glucocorticoids, and one-quarter developed relapse of disease.

Matched MeSH terms: Autoimmune Diseases/immunology