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  1. Cheng HM
    Autoimmunity, 1994;19(2):127-33.
    PMID: 7772702 DOI: 10.3109/08916939409009540
    Matched MeSH terms: Antibodies, Antiphospholipid/blood; Antibodies, Antiphospholipid/immunology*
  2. Islam MA, Alam F, Cavestro C, Calcii C, Sasongko TH, Levy RA, et al.
    Autoimmun Rev, 2018 Aug;17(8):755-767.
    PMID: 29885542 DOI: 10.1016/j.autrev.2018.01.025
    BACKGROUND: Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive.

    AIMS: The aim of this systematic review and meta-analysis was to evaluate the presence of aPLs in epileptic patients as compared to healthy controls.

    METHODS: Five electronic databases (PubMed, Web of Science, Embase, Scopus and Google Scholar) were searched systematically. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). L'Abbé plots were generated to visually inspect heterogeneity while publication bias was evaluated via visualization of contour- enhanced funnel plots, and Begg's and Egger's tests.

    RESULTS: Based on the inclusion criteria, 14 studies were selected involving 1248 epilepsy patients and 800 healthy controls. The majority of epilepsy was categorised as generalised or partial and none had comorbidity with autoimmune diseases. Significant presence of both anticardiolipin (aCL) antibodies (OR: 5.16, 95% CI: 3.21-8.28, p 
    Matched MeSH terms: Antibodies, Antiphospholipid/immunology*
  3. Ismail R, Cheng HM
    Thromb Res, 1994 Jan 15;73(2):143-7.
    PMID: 8171414 DOI: 10.1016/0049-3848(94)90090-6
    Matched MeSH terms: Antibodies, Antiphospholipid/pharmacology*
  4. Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH
    CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
    PMID: 27658514 DOI: 10.2174/1871527315666160920122750
    Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
    Matched MeSH terms: Antibodies, Antiphospholipid/blood; Antibodies, Antiphospholipid/metabolism*
  5. Islam MA, Alam SS, Kundu S, Prodhan AHMSU, Khandker SS, Reshetnyak T, et al.
    PLoS One, 2020;15(1):e0227836.
    PMID: 31929597 DOI: 10.1371/journal.pone.0227836
    Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-β2-glycoprotein I (β2-GPI) antibodies and lupus anticoagulant (LA) are detected in systemic autoimmune diseases which contribute to thrombosis. The aim of this systematic review and meta-analysis was to evaluate the prevalence of aPLs in patients with BD as compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42018088125) and a systematic literature search was conducted through PubMed, Web of Science, Embase, Scopus and ScienceDirect databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualisation of contour- enhanced and trim and fill funnel plots along with Begg's and Egger's tests. We included ten case-control studies (a total of 999 participants from 380 BD patients and 619 controls) based on the inclusion criteria. The prevalence of aCL (OR: 12.10, 95% CI: 5.15-28.41, p<0.00001) and anti-β2-GPI antibodies (OR: 23.57, 95% CI: 1.31-423.63, p = 0.03) were statistically significant, however, the prevalence of LA was not significant (OR: 13.77, 95% CI: 0.65-293.59, p = 0.09). The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 50.0% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's and Egger's tests. This meta-analysis established that there is a significantly high prevalence of aPLs (i.e., aCL and anti-β2-GPI antibodies) in patients with BD when compared to controls.
    Matched MeSH terms: Antibodies, Antiphospholipid/blood; Antibodies, Antiphospholipid/immunology*
  6. Islam MA, Alam F, Wong KK
    Autoimmun Rev, 2017 May;16(5):512-522.
    PMID: 28279839 DOI: 10.1016/j.autrev.2017.03.005
    BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients.

    AIMS: The aim of this study was to evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls.

    METHODS: Studies were searched through PubMed, ISI Web of Science and Google Scholar databases without restricting the languages and year (up to October 2016) and were selected based on the inclusion criteria. Two authors independently extracted data from the included studies. All analyses were conducted by using random effects model to calculate the odds ratio (OR) and 95% confidence interval (CI). Quality assessment was carried out by using the modified Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualization of funnel plots, Begg's and Egger's tests.

    RESULTS: The database searches produced 1995 articles, 13 of which were selected (912 migraineurs and 822 healthy controls). 8.59%, 15.21% and 4.11% of the migraineurs exhibited aCL, anti-β2GPI and LA which was 4.83, 1.63 and 3.03 times higher, respectively, than healthy controls. A significant presence of aCL (OR: 3.55, 95% CI: 1.59-7.95; p=0.002) or anti-β2GPI antibodies (OR: 2.02, 95% CI: 1.20-3.42; p=0.008) was observed in migraine patients, however, LA was not significantly associated (OR: 2.02, 95% CI: 0.50-8.37; p=0.320). Majority of the studies (n=10 of 13) demonstrated NOS score of 7 or above and no significant publication bias was observed.

    CONCLUSION: Migraine might be an autoimmune-associated neurologic disorder. The presence of aCL or anti-β2GPI antibodies was significant in migraine patients compared to healthy controls, suggesting an involvement of these autoantibodies in migraine attack.
    Matched MeSH terms: Antibodies, Antiphospholipid/adverse effects*; Antibodies, Antiphospholipid/immunology
  7. Teh CL, Leong TS
    Clin Rheumatol, 2015 Jan;34(1):175-8.
    PMID: 24831689 DOI: 10.1007/s10067-014-2671-6
    We performed a cross-sectional study of all antiphospholipid syndrome (APS) patients during an 8-year period (2006-2013) to describe the clinical features, serology profiles, treatment regimes, and outcomes in our center. There were a total of 59 patients in our study with the female to male ratio of 9:1. They have a mean age of 41.6 ± 12.1 years and a mean duration of illness of 38.4 ± 68.5 months. The majority of patients presented with vascular thrombosis (69.5 %) with equal arterial and venous involvements. Twenty-six patients (44.1 %) presented with obstetric complications with recurrent abortions (32.2 %) as the main manifestation. Most patients were on daily warfarin doses of 2-6 mg (91.0 %) with target INR of 2-3. There was neither recurrent thrombosis nor bleeding complications documented. There were 80 % live births following treatment in our patients.
    Matched MeSH terms: Antibodies, Antiphospholipid/blood*
  8. Ching YM, Arip M, Jegasothy R, Baskaran TP, Yusof AY, Bakhtiar F, et al.
    Malays J Pathol, 2013 Dec;35(2):147-51.
    PMID: 24362478 MyJurnal
    The presence of antiphospholipid antibodies (aPLs) is closely associated with thrombotic events and pregnancy complications such as recurrent pregnancy loss, preeclampsia and placental insufficiency. We investigated the presence of aPLs and its frequency among female patients with a history of fetal loss in a Malaysia population. Serum samples were collected from 108 patients who had (1) one or more unexplained deaths of morphologically normal fetuses at or beyond the 22nd week of gestation, or (2) one or more premature births of morphologically normal neonates at or before the 24th week of gestation due to eclampsia or preeclampsia, or recognized features of placental insufficiency, or (3) three or more unexplained, consecutive, spontaneous miscarriages before the 20th week of gestation. Serum was tested for aPLs subtypes: anticardiolipin (aCL), anti-beta-2- glycoprotein I (aβ2GPI), anti-beta-2-glycoprotein I dependent cardiolipin (aβ2GPI dependent CL), anti-phosphatidylcholine (aPC), anti-phosphatidylethanolamine (aPE), anti-phosphatidylinositol (aPI), anti-phosphatidylserine (aPS) and anti-sphingomyeline (aSph) by using the enzyme-linked immunosorbent assay (ELISA) method. The mean age of patients was 30±5. Four patients (3.7%) were found positive for at least one aPLs subtype. Four aPLs subtypes were detected. The most common subtypes was aβ2GPI dependent CL (3.7%), followed by aCL (2.7%), aβ2GPI (0.9%), and aPE(0.9%). In conclusion, frequency of aPLs among women with fetal loss (3.7%) in Malaysia was low with subtype aβ2GPI dependent CL being the most prevalent aPLs.
    Matched MeSH terms: Antibodies, Antiphospholipid/blood*
  9. Islam MA, Alam F, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(28):4451-69.
    PMID: 27229722
    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear. Therefore, patients are treated with anticoagulant and/or antiplatelet regimens just as in other thrombotic disorders even though the thrombotic pathophysiology is mainly aPLs-mediated. In this review, we provided an update of the cellular, auto-immune and genetic factors known to play important roles in the generation of thrombi. Current successful regimens are also outlined along with potential emerging treatment strategies that may lead to the optimum management of thrombotic APS patients.
    Matched MeSH terms: Antibodies, Antiphospholipid/immunology*
  10. Lee MK, Cheng HM, Ng SC, Menaka N, Tan CT, Wang F
    Med J Malaysia, 1993 Sep;48(3):330-5.
    PMID: 8183147
    Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.
    Matched MeSH terms: Antibodies, Antiphospholipid/blood*
  11. Sugai S
    Curr Opin Rheumatol, 1992 Oct;4(5):666-71.
    PMID: 1419500
    Over the past year, many reports have been published on a variety of clinical manifestations related to antiphospholipid antibodies. The low prevalence of anticardiolipin antibodies with the rare occurrence of thrombosis and a low rate of fetal loss in studies in Malaysia and China showed a potential role for local factors. A study of cross-reactive idiotype of the anticardiolipin antibody suggested that anticardiolipin antibodies are derived from a set of natural autoreactive clones. Regarding the pathogenic role of the antiphospholipid antibody, evidence has been presented that the epitopes formed between cardiolipin and beta 2 glycoprotein I are the targets of the antiphospholipid antibody. Complement activation, abnormalities of natural anticoagulants such as protein S deficiency, and genetic association with DR4, DR7, and DRw53 have also been studied.
    Matched MeSH terms: Antibodies, Antiphospholipid*
  12. Islam MA
    Semin Cancer Biol, 2020 08;64:108-113.
    PMID: 31351197 DOI: 10.1016/j.semcancer.2019.07.019
    Antiphospholipid antibodies (aPLs) are autoantibodies with laboratory significance in developing thrombosis and pregnancy morbidity in antiphospholipid syndrome (APS). High prevalence of aPLs namely - anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant, antiphosphatidylcholine, antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidylethanolamine and antiprothrombin antibodies have been observed in patients with different types of haematological malignancies and solid tumours. Although cancer patients have high risk of developing thrombosis, the risk becomes even higher in aPLs carriers. Although the relationship between aPLs and cancer has to be further investigated, however, the presence of aPLs in neoplastic patients can possibly increase the risk of developing thrombosis. As the pathogenic role of aPLs in cancer is still a matter of debate, more researches should be conducted on the association between the aPLs and malignancies towards the potential impact on understanding the pathogenicity and treatment when cancer and APS coexists.
    Matched MeSH terms: Antibodies, Antiphospholipid/immunology*
  13. Cheng HM, Ngeow YF
    Int Arch Allergy Immunol, 1993;101(3):297-8.
    PMID: 8324391
    Matched MeSH terms: Antibodies, Antiphospholipid/immunology*
  14. Barber BE, Grigg MJ, Piera K, Amante FH, William T, Boyle MJ, et al.
    J Infect Dis, 2019 09 26;220(9):1435-1443.
    PMID: 31250022 DOI: 10.1093/infdis/jiz334
    BACKGROUND: Anemia is a major complication of vivax malaria. Antiphosphatidylserine (PS) antibodies generated during falciparum malaria mediate phagocytosis of uninfected red blood cells that expose PS and have been linked to late malarial anemia. However, their role in anemia from non-falciparum Plasmodium species is not known, nor their role in early anemia from falciparum malaria.

    METHODS: We measured PS immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in Malaysian patients with vivax, falciparum, knowlesi, and malariae malaria, and in healthy controls, and correlated antibody titres with hemoglobin. PS antibodies were also measured in volunteers experimentally infected with Plasmodium vivax and Plasmodium falciparum.

    RESULTS: PS IgM and IgG antibodies were elevated in patients with vivax, falciparum, knowlesi, and malariae malaria (P < .0001 for all comparisons with controls) and were highest in vivax malaria. In vivax and falciparum malaria, PS IgM and IgG on admission correlated inversely with admission and nadir hemoglobin, controlling for parasitemia and fever duration. PS IgM and IgG were also increased in volunteers infected with blood-stage P. vivax and P. falciparum, and were higher in P. vivax infection.

    CONCLUSIONS: PS antibodies are higher in vivax than falciparum malaria, correlate inversely with hemoglobin, and may contribute to the early loss of uninfected red blood cells found in malarial anemia from both species.

    Matched MeSH terms: Antibodies, Antiphospholipid/blood*
  15. Islam MA, Alam F, Gan SH, Cavestro C, Wong KK
    Cephalalgia, 2018 03;38(3):568-580.
    PMID: 28952322 DOI: 10.1177/0333102417694881
    Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.
    Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.
    Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p 
    Matched MeSH terms: Antibodies, Antiphospholipid/blood*
  16. Islam MA, Wong KK, Sasongko TH, Gan SH, Wong JS
    Eur J Rheumatol, 2016 Sep;3(3):139-141.
    PMID: 27733946 DOI: 10.5152/eurjrheum.2015.0068
    Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.
    Matched MeSH terms: Antibodies, Antiphospholipid
  17. Ng HK, Chong MF, Azhany Y, Zunaina E
    Clin Ophthalmol, 2014;8:2359-63.
    PMID: 25473262 DOI: 10.2147/OPTH.S71712
    Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease that can affect any part of the human body including the eyes. Common blinding ocular manifestations include central retinal artery occlusion (CRAO), central retinal vein occlusion (CRVO), severe vaso-occlusive retinopathy, and optic nerve involvement. Antiphospholipid syndrome (APS) in lupus is usually associated with large vessel occlusions and needs prompt treatment with anticoagulant. We are reporting two cases of APS in SLE patients that presented with CRVO (case 1) and vaso-occlusive lupus retinopathy (case 2). Both cases were positive for antiphospholipid antibody (APA) and were treated with immunosuppression, anticoagulant, and laser treatment. Thus, screening for APA is vital in SLE patients with lupus retinopathy, as prompt treatment with anticoagulants is important to prevent further vascular thrombosis, which worsens the visual prognosis.
    Study site: Ophthalmology clinic, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia
    Matched MeSH terms: Antibodies, Antiphospholipid
  18. Islam MA, Alam F, Wong KK, Kamal MA, Gan SH
    Curr Vasc Pharmacol, 2017;15(4):313-326.
    PMID: 28056758 DOI: 10.2174/1570161115666170105120931
    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS.
    Matched MeSH terms: Antibodies, Antiphospholipid
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