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Origin and pathogenesis of antiphospholipid antibodies
Celli, C.M.;Gharavi, A.E.;
Brazilian Journal of Medical and Biological Research , 1998, DOI: 10.1590/S0100-879X1998000600002
Abstract: antiphospholipid antibodies (apl) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, aids) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of apl designating the antiphospholipid syndrome. in contrast, apl from patients with infectious disorders are not associated with any clinical manifestation. these findings led to increased interest in the origin and pathogenesis of apl. here we present the clinical features of the antiphospholipid syndrome and review the origin of apl, the characteristics of experimentally induced apl and their historical background. within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.
Origin and pathogenesis of antiphospholipid antibodies  [cached]
Celli C.M.,Gharavi A.E.
Brazilian Journal of Medical and Biological Research , 1998,
Abstract: Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.
Antiphospholipid antibodies: Paradigm in transition
Lawrence L Horstman, Wenche Jy, Carlos J Bidot, Yeon S Ahn, Roger E Kelley, Robert Zivadinov, Amir H Maghzi, Masoud Etemadifar, Seyed Mousavi, Alireza Minagar
Journal of Neuroinflammation , 2009, DOI: 10.1186/1742-2094-6-3
Abstract: After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed.The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology.This manuscript critically compares the many theories and concepts of anti-phospholipid antibodies (aPL) as they pertain to the antiphospholipid syndrome (APS) and other clinical conditions where they occur. This review is not primarily concerned with clinical diagnosis and management, except peripherally. Although the topic of aPL has been reviewed many times, this review was inspired by findings in our laboratory and others suggesting that aPL may play roles in a variety of disorders apart from APS, not necessarily thrombotic.According to Eng [1] and others, it was Pangborn who in 1941, following Wasserman's test for syphilis in 1903, identified an acidic phospholipid (PL) as the apparent target antigen of the test, specifically, cardiolipin (CL). CL is named for the bovine heart muscle from which it was obtained, heart being rich in mitochondria, a main source of CL. In 1952, Conley and Hartmann first described the lupus anticoagulant (LA), later interpreted as a consequence of aPL, in association with a hemorrhagic diathesis [2]. However, this and other early clinical observations were later overshadowed by frequent findings of thrombosis associated with positive anti-CL (aCL) test, leading to recognition of the aPL syndrome (APS) in the 1980s by Harris et al [3,4] and by
Seroprevalence of torch infection in bad obstetric history  [cached]
Turbadkar D,Mathur M,Rele M
Indian Journal of Medical Microbiology , 2003,
Abstract: Primary infection with TORCH complex [Toxoplasma, Rubella, Cytomegalovirus (CMV), and Herpes simplex virus II (HSV-II)] in pregnant women can lead to adverse outcome which are initially inapparent or asymptomatic and thus difficult to diagnose on clinical grounds. Over a one-year period 380 serum samples were collected from pregnant women having bad obstetric history, attending antenatal clinic. In the present study we have shown the prevalence of Toxoplasma, Rubella, CMV, HSV-II infection in pregnant women by demonstrating the presence of IgM and IgG antibodies by ELISA test. It was found that, IgM antibodies were positive in 40 (10.52%) for Toxoplasma, 102 (26.8%) for Rubella, 32 (8.42%) for CMV and 14 (3.6%) for HSV-II. IgG antibodies were positive in 160 (42.10%) for Toxoplasma, 233 (61.3%) for Rubella, 346 (91.05%) for CMV 145 (33.58%) for HSV-II. Hence all antenatal cases with bad obstetric history should be routinely screened for TORCH as early diagnosis and appropriate intervention, will help in proper management of these cases.
Genome-Wide Association Study of Antiphospholipid Antibodies  [PDF]
M. Ilyas Kamboh,Xingbin Wang,Amy H. Kao,Michael M. Barmada,Ann Clarke,Rosalind Ramsey-Goldman,Susan Manzi,F. Yesim Demirci
Autoimmune Diseases , 2013, DOI: 10.1155/2013/761046
Abstract: Background. The persistent presence of antiphospholipid antibodies (APA) may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS) in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL), lupus anticoagulant (LAC), and anti-β2 glycoprotein I antibodies (anti-β2GPI). Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs). Association of SNPs with the antibody status (positive/negative) was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with . Although they do not meet the conservative threshold of genome-wide significance, many of the suggestive loci are potential candidates for the production of APA. We have replicated the previously reported associations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings. 1. Introduction Antiphospholipid antibodies (APA) are a heterogeneous group of antibodies that are detected in a variety of conditions, including primary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) [1]. The term antiphospholipid antibodies is a misnomer as APA present in autoimmune disease, like SLE, do not bind to phospholipids but recognize phospholipid-binding proteins [2]. Patients with persistent APA who develop pregnancy complications or thrombosis are considered to have primary APS and those who develop these complications in the presence of autoimmune disease are classified having secondary APS. Since the definition of APS is not limited to a single APA assay, it is required to measure more than one APA. Indeed, currently recognized laboratory criteria for APS include having one or more of three APA, including anticardiolipin antibodies (ACL), lupus anticoagulant (LAC), or anti-β2 glycoprotein I antibodies (anti-β2GPI) in conjunction with the presence of thrombosis or pregnancy loss [3]. Although the genetic basis of APA [4] and APS [5] has been suggested, the underlying genetic factors have not been clearly established. Understanding the genetic bases of various APA may help to delineate the mechanisms for APS. The objective of this study was to
Antiphospholipid antibodies syndrome in ′Stroke in young′.  [cached]
Mehndiratta M,Bhattacharya A,Gupta M,Khawaja G
Neurology India , 1999,
Abstract: Antiphospholipid antibodies syndrome has emerged as an important entity responsible for stroke in young. Seven cases of young stroke (< 40 years of age) with mean age of 30.1 years (age range 25-39 years, 2 males and 5 females), who tested positive for antiphospholipid antibodies are being reported. All subjects had completed strokes. Six had arterial ischaemic and one patient had venous stroke. One patient suffered from four episodes, three ischaemic and one intracerebral haemorrhage. Two patients suffered from foetal loss. Generalised tonic clonic seizures occurred in three patients. Deep vein thrombosis was observed in one case. Thrombocytopenia was not observed in any case. All the patients had elevated anticardiolipin antibodies (aCL) IgM or IgG, while Lupus anticoagulant (LA) was elevated in 4 cases. Six cases belonged to primary antiphospholipid antibodies syndrome and one to lupus like illness. Oral anticoagulants were administered to maintain a high intensity international normalized ratio (INR). No recurrences were observed during a follow up period of 6-18 months.
Study of TORCH profile in patients with bad obstetric history  [PDF]
MS Sadik
Biology and Medicine , 2012,
Abstract: Infections caused by TORCH complex - Toxoplasma gondii, Rubella virus, cytomegalovirus (CMV), and herpes simplex virus (HSV) - are causes of bad obstetric history (BOH). TORCH infections are generally mild in the mother but can prove disastrous to the fetus. The degree of severity depends on the gestational age of the fetus; when infected, the virulence can damage the fetus in the developmental stages and also increase the severity of maternal disease. The aim of this study was to evaluate the incidence of TORCH infections in pregnancy wastage in women with BOH in south Indian population. This study reports the prevalence of Toxoplasma, Rubella, CMV, and HSV-II infections in randomly selected 86 pregnant women by demonstrating the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies using ELISA kits. Immunoglobulin M antibodies were positive in six patients (6.97%) for Toxoplasma, four (4.65%) for Rubella, Nil for CMV, and one (1.69%) for HSV-II. Immunoglobulin G antibodies were positive in 18 patients (20.93%) for Toxoplasma, 25 (29.06%) for Rubella, 20 (23.25%) for CMV, and 16 (18.60%) for HSV-II. It was evident that among the TORCH pathogens, our study group did suffer from Toxoplasma and Rubella to a larger extent compared with CMV and HSV-II viruses. Hence, from this study, we conclude that all antenatal cases with BOH should be routinely screened for TORCH for early diagnosis so that appropriate intervention at early stages can help in proper management of these cases.
Immune status in infection by cytomegalovirus in women with bad obstetric history  [PDF]
D Acharya,S Shrestha,B Bogati,JB Sherchan,P Karki,A Yadav,SK Madhup,NR Tuladhar
International Journal of Infection and Microbiology , 2013, DOI: 10.3126/ijim.v2i1.7663
Abstract: Introduction: Viral infections during pregnancy carry a risk for intrauterine transmission which may result in fetal damage. Bad obstetric history implies for previous unfavorable foetal outcome in terms of two or more consecutive spontaneous abortions, history of intrauterine foetal death, intrauterine growth retardation, still birth, early neonatal death and congenital anomalies. Cytomegalovirus, a ubiquitous virus belonging to the herpes family, is known to cause abnormal fetal outcome. We aim to determine the possible involvement of CMV infection among pregnant women with bad obstetric history Materials and Methods: A cross sectional study was carried out among 136 women with bad obstetric outcome attending Dhulikhel Hospital- Kathmandu University Hospital. The cytomegalovirus specific IgG and IgM antibodies were determined by ELISA test. Data were analyzed using SPSS, version 17.0 and interpreted according to frequency distribution and percentage. The data was considered significant if the p-value was <0.05. Results: The results revealed that 87 (63.9%) out of 136 patients were positive for CMV IgG antibodies and only one (0.007%) patient was positive for CMV IgM. The majority of the patients were of the age between 20 and 29 years (99/136) and it was observed that most of the positive CMV IgG were participants of the same age group (63/ 99). There was no significant association of CMV seropositivity with the age of participants (p value 0.9). Conclusion: CMV infection could be the risk factor for BOH and may play a vital role in determining the foetal outcome. Thus we recommend routine serological testing to all pregnant women with or without BOH attending the antenatal clinics for both CMV specific IgG and IgM. DOI: http://doi.dx.org/10.3126/ijim.v2i1.7663 Int J Infect Microbiol 2013;2(1):3-6
Antiphospholipid antibodies and multiple organ failure in critically ill cancer patients
Salluh, Jorge I. F.;Soares, Márcio;Meis, Ernesto De;
Clinics , 2009, DOI: 10.1590/S1807-59322009000200003
Abstract: objectives: to describe the clinical outcomes and thrombotic events in a series of critically ill cancer patients positive for antiphospholipid (apl) antibodies. design: retrospective case series study. setting: medical-surgical oncologic intensive care unit (icu). patients and participants: eighteen patients with sirs/sepsis and multiple organ failure (mof) and positive for apl antibodies, included over a 10-month period. interventions: none measurements and results: apl antibodies and coagulation parameters were measured up to 48 hours after the occurrence of acrocyanosis or arterial/venous thrombotic events. when current criteria for the diagnosis of apl syndrome were applied, 16 patients met the criteria for "probable" and two patients had a definite diagnosis of apl syndrome in its catastrophic form (caps). acrocyanosis, arterial events and venous thrombosis were present in eighteen, nine and five patients, respectively. sepsis, cancer and major surgery were the main precipitating factors. all patients developed mof during the icu stay, with a hospital mortality rate of 72% (13/18). five patients were discharged from the hospital. there were three survivors at 90 days of follow-up. new measurements of lupus anticoagulant (lac) antibodies were performed in these three survivors and one patient still tested positive for these antibodies. conclusions: in this small series of patients, we observed a high frequency of auto-antibodies and micro- and macro-vascular thrombotic events in critically ill cancer patients. the coexistence of sepsis or sirs and apl antibodies was often associated with mof and death. more studies are necessary to determine the pathophysiological significance of antiphospholipid antibodies in severely ill cancer patients.
Antiphospholipid Antibodies in Egyptian Patients with Chronic Renal Failure
Samiha Abo El Yazeed,Nagwa Abd EL-Ghaffar,Khaled Younes,Ahmed El-Ghobary
Journal of Medical Sciences , 2006,
Abstract: The objectives of present research was to detect the incidence of antiphospholipid antibodies among Egyptian patients with chronic renal failure and its relation to their clinical manifestation and vascular access thrombosis. This study including 80 patients with chronic renal disease divided into two groups. Group A, forty patients with impaired renal function and group B, forty patients in chronic renal failure on hemodialysis. In addition to 10 age and sex matched subjects as a control group. All of them were subjected to clinical examination and laboratory investigation including antiphospholipid antibodies. Lupus anticoagulant was present in 21.25%, aCL IgM in 18.75% while aCL IgG in 11.25% of whole chronic renal disease patients. There was higher incidence of antiphospholipid antibodies in-group B end stage renal failure on hemodialysis (28/40(70%)) compared to group A of renal impairment (25/40(62.5%)). Also there was insignificant relationship between antiphospholipid antibodies and age, kidney function or liver function tests. There is increase of antiphospholipid antibodies among patients with chronic renal failure with great liability for thrombosis of vascular access. Also patients with positive LA have a great possibility to be hypertensive. HCV infection in hemodialysis group may be the cause of increased incidence of antibodies. Antiphospholipid antibody profile should be done for patients with recurrent thrombosis of vascular shunt, as it is the main cause of hospitalization of dialysis patients.
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