Detection of antiphospholipid antibody levels in normal pregnant women by chemiluminescence immunoassay and comparison between different trimesters / 中华围产医学杂志

Objective:Chemiluminescence immunoassay was used to detect the levels of anticardiolipin antibody (aCL) -IgA/IgG/IgM and anti-β2-glycoprotein Ⅰ antibody (aβ2GPⅠ) -IgA/IgG/IgM in healthy non-pregnant and pregnant women to explore the changes of antiphospholipid antibody in different pregnancy periods.Methods:This prospective study was conducted in Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, involving normal pregnant women who underwent prenatal examination and healthy non-pregnant women with no history of adverse pregnancy who underwent progestational eugenic health examination from April 2020 to August 2021. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM were detected using BIO-FLASH chemiluminescence immunoassay analyzer and P95 as well as P99 were calculated, respectively. The difference in the six data between non-pregnant and pregnant women was compared using Mann-Whitney U test. Kruskal-Wallis H test was used to compare the change of each antibody in different pregnancy periods and Spearman correlation was used to analyze the correlation between different trimester and the levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM. Results:A total of 454 cases met the inclusion criteria, and 435 cases were included in the analysis after excluding 19 cases, among them 110 were non-pregnant women and 325 were pregnant women, including 110 cases in the first trimester (≤13 +6 weeks), 110 cases in the second trimester(14 +0-27 +6 weeks), and 105 cases in the third trimester (≥28 weeks). P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM in the non-pregnant women were 7.31, 14.70, 7.92, 3.58, 13.60, and 4.95 CU, which in the pregnant women were 5.90, 12.78, 5.70, 1.60, 10.65, and 3.90 CU, and were all lower than the cut-off value of 20 CU that given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM, and aβ2GPⅠ-IgG/IgM in the pregnant women were significantly decreased comparing with the non-pregnant women [aCL-IgA: 1.90 CU (1.40-2.70 CU) vs 2.90 CU (2.20-3.83 CU), Z=－7.14; aCL-IgG: 3.00 CU (2.20-4.50 CU) vs 6.10 CU (4.20-7.83 CU), Z=－10.26; aCL-IgM: 1.40 CU (1.10-2.30 CU) vs 2.65 CU (2.08-3.73 CU), Z=－8.87; aβ2GPⅠ-IgG: 3.50 CU (2.60-4.90 CU) vs 4.75 CU (3.60-5.93 CU), Z=－5.45; aβ2GPⅠ-IgM: 0.70 CU (0.50-1.20 CU) vs 1.00 CU (0.60-1.53 CU) , Z=－3.73; all P<0.001]. The aCL-IgA level in the third trimester was higher than those in the first and second trimester (both P<0.05). The levels of aCL-IgG/IgM in the second trimester and aβ2GPⅠ- IgG in the second and third trimesters were significantly decreased than those in the first trimester (all P<0.05). Spearman analysis showed that aCL-IgG/IgM, aβ2GPⅠ-IgA/IgM had no significant correlation with the pregnancy period (the first, second and the third trimester) (all P>0.05). However, a weak correlation between the aCL-IgA, aβ2GPⅠ- IgG and the pregnancy period was observed ( r=0.28 and－0.49, both P<0.001) Conclusions:P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM levels in normal pregnant women and non-pregnant women are lower than the cut-off value of 20 CU given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgG/IgM during pregnancy are lower than those before pregnancy and fluctuate with the pregnancy period, but have no significant correlation with the pregnancy period. The clinical diagnosis of antiphospholipid syndrome should be made according to the cut-off values of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM determined by each laboratory.

Correlations of anti-cardiolipin antibody and anti-β2 glycoprotein I antibody with ischemic stroke in patients with systemic autoimmune diseases / 中国基层医药

Objective:To correlate anti-cardiolipin antibody (aCL) and anti-β2 glycoprotein I antibody (aβ2GPI) with ischemic stroke (IS) in patients with systemic autoimmune diseases (SADs).Methods:A total of 104 patients with SADs who received treatment in the Affiliated Hospital of North Sichuan Medical College during January to December 2019 were included in this study. They were divided into two groups whether they had IS (IS group, n = 42) or not (non-IS group, n = 62). aPL positive rate was qualitatively compared between the IS and non-IS groups. aCL and aβ2GPI expression levels were quantitatively compared between the IS and non-IS groups. Logistic regression analysis was performed to evaluate the risk factors for IS in patients with SADs. Results:aPL positive rate in the IS group was significantly higher than that in the non-IS group [61.9% (26/42) vs. 40.3% (25 /62), χ2 = 4.66, P = 0.031]. The aCL-IgM and aβ2GPI-IgM levels in the IS group were (22.82 ± 27.27) RU/mL and (18.70 ± 23.95) RU/mL, respectively, which were significantly higher than those in the non-IS group [(13.34 ± 8.43) RU/mL, (7.61± 5.80) RU/mL, t = -2.18, -2.76, P = 0.034, 0.009]. Logistic regression analysis showed that aPL is an independent risk factor for IS ( P = 0.037). Conclusion:aCL and aβ2GPI are closely related to the occurrence of IS and are the independent risk factors for IS in patients with SADs.

Systemic lupus erythematosus with extensive intracranial calcification: a case report / 中华神经科杂志

Extensive intracranial calcification is rare in patients with systemic lupus erythematosus. This article reported a patient with antiphospholipid antibody syndrome secondary to systemic lupus erythematosus, complicated with bilateral symmetrical extensive intracranial calcification. By reviewing literature, the results suggested that the flare of neuropsychiatric systemic lupus erythematosus and the presence of antiphospholipid antibodies may be risk factors for intracranial calcification. Therefore, in order to prevent the formation of intracranial calcification, it is necessary to maintain continuous disease remission and anticoagulant therapy.

Non-criteria Antiphospholipid Antibodies: a narrative review

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

RESUMO A classificação de Sapporo revisada para a síndrome antifosfolipídica definida de 2006 incluiu como critérios laboratoriais aqueles testes para anticorpos antifosfolípides cuja acurácia era considerada satisfatória de acordo com a evidência então disponível. Porém, na prática, a sensibilidade e especificidade desses anticorpos antifosfolípides "critério" são por vezes insuficientes para identificar ou descartar a síndrome antifosfolípide. Tem-se estudado se a acurácia do diagnóstico laboratorial da síndrome poderia ser melhorada por meio da testagem de anticorpos antifosfolípides não critério. Neste trabalho revisamos a evidência a respeito das associações clínicas e valor diagnóstico dos anticorpos não critério mais estudados, nomeadamente: anticorpos antifosfatidiletanolamina, antianexina A5, antiprotrombina, anticomplexo fosfatidilserina/protrombina, IgA anticardiolipina e IgG antidomínio I da anti-β2 glicoproteína I.

Clinical study of Jiawei-Cuyun Decoction on autoimmunity recurrent spontaneous abortion in recurrent spontaneous abortion / 国际中医中药杂志

Objective@#To observe the effect of Jiawei-Cuyun Decoction on autoimmunity recurrent spontaneous abortion in recurrent spontaneous abortion.@*Methods@#To include eighty patients with autoimmunity recurrent spontaneous abortion from January 2016 to January 2018 in our hospital. The patients were divided into treatment group (36 cases) and control group (44 cases). The control group was treated with aspirin, and the treatment group was treated with Jiawei-Cuyun Decoction. The two groups, who were in the menstrual cycle, both were treated for 5 days until menstruation ends. The course of treatment for pregnancy should be no more than 3 menstrual cycles, and after pregnancy, the treatment should continue until the end of 12 weeks of pregnancy. During three menstrual cycles, the pregnancy serum anticardiolipin (aCL), anti-β2-1 glycoprotein (aβ2GP1) IgG and IgM were detected, and the adverse of drugs and pregnancy outcomes were recorded.@*Results@#For the third menstrual cycle, the overcast rates of serum aCL IgG [94.4% (34/36) vs. 68.2% (30/44); χ2=5.501, P=0.019], IgM [94.4% (34/36) vs. 77.3% (34/44); χ2=4.579, P=0.032], aβ2GP1 IgG [94.4% (34/36) vs. 75.0% (33/44); χ2=4.165, P=0.041], IgM [97.2% (35/36) vs. 79.5% (35/44); χ2=4.156, P=0.042] in the treatment group were significantly higher than those in the control group. After the treatment, the incidence of adverse reactions of the treatment group was 5.6% (2/36), and the control group was 31.8% (14/44), which showed that there was statistically significant difference between two groups (χ2=8.535, P=0.004). Pregnancy success rate of treatment group was 80.6% (29/36), and the control group was 56.8% (25/44), which showed that there was statistically significant difference between two groups (χ2=4.061, P=0.044).@*Conclusions@#Jiawei-Cuyun Decoction can effectively reduce the aCL, aβ2GP1 is IgG and IgM positive expression, reduce adverse drug reactions and improve the successful rate of pregnancy.

Research progress of relationship between anticardiolipin antibody and ischemic stroke / 心血管康复医学杂志

Ischemic stroke is a most frequent type of cerebrovascular disease .In recent years ,along with continuous deepening research on cause of cerebrovascular diseases ,autoimmune—mediated cerebrovascular diseases receive a lot of attention .Researches have found that anticardiolipin antibody (ACA) plays an important role in pathogenesis of ischemic stroke .The present article made following review on relationship between ACA and ischemic stroke and its current situation of research .

Clinical Phenotype of a First Unprovoked Acute Pulmonary Embolism Associated with Antiphospholipid Antibody Syndrome / 결핵및호흡기질환

BACKGROUND: Antiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS. METHODS: We retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006–2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups. RESULTS: On multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025–162.343), low PE severity index (OR, 0.948; 95% CI, 0.917–0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040–1.307). Model II included age (OR, 0.930; 95% CI, 0.893–0.969) and aPTT (OR, 1.104; 95% CI, 1.000–1.217). CONCLUSION: We conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I–II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.

The antiphospholipid antibodies and pathological pregnancy / 中华检验医学杂志

Antiphospholipid antibody is a kind of autoantibodies that can react with different phospholipid components of the body .Many researches have suggested that antiphospholipid antibody can lead to many pathological pregnancies such as recurrent miscarriage , premature birth, stillbirth, pre-eclampsia by promoting placental thrombosis , damaging the functions trophoblast cells and many other pathways.Appropriate anticoagulation and immunotherapy in patients with pathological pregnancy induced by antiphospholipid antibodies can significantly improve the outcome of pregnancy .

Clinical analysis of 12 patients with pediatric antiphospholipid syndrome with pulmonary embolism / 中华儿科杂志

Objective@#To identify the clinical and immunological characteristics of pediatric antiphospholipid syndrome (APS) patients with pulmonary embolism.@*Method@#Among 47 pediatric APS patients from Peking Union Medical College Hospital during the year of 2000 to 2015, 12 patients were diagnosed of pulmonary embolism, who were investigated and compared with APS patients without pulmonary embolism.@*Result@#Twelve patients (among whom 6 cases were primary and the other 6 were secondary APS)had pulmonary embolism and all of them were non-shock type, which was the first presenting manifestation in 6 of them.Eight cases were misdiagnosed as infection, while 3 cases were missed.Among patients with pulmonary embolism, 10 patients suffered from deep vein thrombosis at the same time, mainly in lower extremities.2 cases had thrombotic recurrence, which happened only in primary APS patients, because of irregular monitoring of International Normalized Ratio, or not taking aspirin after quitting warfarin.Positive anticardiolipin (ACL) and lupus anticoagulant (LA) were found in 10 and 9 patients respectively.Four primary APS patients had positive anti-nuclear antibodies (ANA). During follow-up of 3-100 months (median 23 months) of primary APS, no one had evolved manifestations of systemic lupus erythematosus.Primary APS was more often seen in males (M∶F 5∶1 vs. 0∶6) and the patients were much younger ((15±1) vs. (17±0) years old) than those with secondary APS.Besides that, no statistically significant difference was seen between primary and secondary APS (P all>0.05). Compared with APS patients without pulmonary embolism, pulmonary hypertension was more common in patients suffered from pulmonary embolism (3/12 vs. 0, P<0.05).@*Conclusion@#Pulmonary embolism can be the first symptom in pediatric APS patients and all of them are non-shock type, which tends to be misdiagnosed or missed. A majority of them suffer from deep vein thrombosis in the lower extremities.Rethrombosis takes place when the anticoagulant therapy is irregular.Positive anti-nuclear antibodies can be seen in primary APS patients, but no manifestations of lupus come out during follow-up.There is no significant difference between primary APS and secondary APS.Pulmonary hypertension is more common in APS patients suffered from pulmonary embolism.

Lúpus eritematoso sistêmico e gravidez: uma revisão da literatura / Lupus erythematosus and pregnancy: a review of the literature

INTRODUÇÃO: O lúpus eritematoso sistêmico (LES) é uma doença autoimune, crônica, com envolvimento variável dos órgãos, principalmente pele e articulações, que afeta, predominantemente, mulheres jovens em idade reprodutiva associação do lúpus eritematoso sistêmico e gravidez é relativamente frequente, uma vez que não há diminuição da fertilidade nas pacientes. OBJETIVOS: Revisar as evidências disponíveis na literatura a cerca das situações clínicas e complicações que podem ocorrer durante o período gestacional de pacientes com lúpus eritematoso sistêmico, como a Síndrome do Anticorpo Antifosfolípide (SAF), a nefrite lúpica e o lúpus neonatal, a correlação entre a atividade do lúpus eritematoso sistêmico e a gravidez, além do uso de medicamentos no período da gestação. MÉTODOS: Foram utilizados banco de dados da Medline, Lilacs, Conchrane, Science Direct e PubMed, fazendo a seleção de artigos de revisão e estudos clínicos randomizados. Foram selecionados 23 artigos dos últimos 10 anos, sendo 21 na língua inglesa e 2 na língua portuguesa, seguindo a classificação Qualis (Capes): A1, A2 e B1. RESULTADOS: Estudos demonstraram a o impacto negativo da gravidez sobre a atividade da doença. Abortamento, natimorto, bebês pequenos para a idade gestacional, prematuridade e pré-eclâmpsia são as principais complicações que podem ocorrer na gestação de paciente com lúpus eritematoso sistêmico. As principais complicações relacionadas à Síndrome do Anticorpo Antifosfolípide relatadas na literatura foram aborto fetal precoce, início precoce de pré-eclâmpsia, retardo do crescimento intrauterino, descolamento prematuro da placenta e parto prematuro. Em relação aos medicamentos, os estudos apontam para a necessidade do uso da aspirina e da heparina de baixo peso molecular para a profilaxia de complicações da Síndrome do Anticorpo Antifosfolípide na gravidez, além do uso dos corticosteroides fluorados para o tratamento da doença em atividade. O uso da hidroxicloroquina em caso de atividade da doença durante a gestação também está indicado. Foram encontradas divergências quanto ao uso da azatioprina e da ciclofosfamida, havendo consenso quanto à contraindicação do metotrexato. CONCLUSÃO: A exacerbação do lúpus eritematoso sistêmico ocorre principalmente quando a doença não está bem controlada, sendo importante o aconselhamento destas pacientes, para que a concepção ocorra apenas quando o lúpus eritematoso sistêmico estiver inativo por pelo menos seis meses. O lúpus A nefrite lúpica, o lúpus neonatal e Síndrome do Anticorpo Antifosfolípide são condições que podem estar presentes em gestação de paciente com lúpus eritematoso sistêmico. A hidroxicloroquina não deve ser interrompida para que não haja exacerbação da doença. A maioria dos imunossupressores, como o metrotrexato e a ciclofosfamida, são contraindicados na gravidez.

INTRODUCTION: The systemic lupus erithematosus (SLE) is a autoimmune disease, chronic, with variable involvement of organs, especially skin and joints, which predominantly affects young women of reproductive age. The association of Systemic Lupus Erithematosus and pregnancy is relatively frequent, since there is no decrease in patients fertility. GOALS: Review the evidence in the literature about the clinical situations and complications that can occur during pregnancy in patients with Systemic Lupus Erithematosus, like the Antiphospholipid Antibody Syndrome (APS), thelupus nephritis and the neonatal lupus, the correlation between the activity of lupus and pregnancy, besides the use of drugs in the period of gestation. METHODS: Were used database from Medline, Lilacs, Cochrane, Science Direct and PubMed, making the selection of review articles and randomized clinical trials. Twenty-three articles were select, published over the past 10 years, with 21 in the English language and 2 in Portuguese, following the Qualis classification (Capes): A1, A2 e B1. RESULTS: Most articles show a negative impact of pregnancy on the disease activity. Abortion, stillbirth, small babies for the gestational age, preterm birth and preeclampsia are the major complications that may occur in pregnant patients with Systemic Lupus Erithematosus. Major complications related to APS in the literature were early miscarriage, early onset preeclampsia, intrauterine growth retardation, placental abruption and preterm delivery. Among medications used to treat Systemic Lupus Erithematosus and related diseases, aspirin and low molecular weight heparin may be used for the prophylaxis of complications of Antiphospholipid Antibody Syndrome and fluorinated corticosteroids for the reatment of disease activity. Hydroxychloroquine is also indicated to treat Systemic Lupus Erithematosus exacerbation during pregnancy. Differences were found, regarding the use of azathioprine and cyclophosphamide. However there is consensus regarding the contraindication of methotrexate. CONCLUSIONS: The exacerbation of Systemic Lupus Erithematosus occurs mainly when it is not well controlled. Being important the counseling of these patients that conception should occur at least after 6 months of inactivity. Nephritis, neonatal lupus and Antiphospholipid Antibody Syndrome are conditions that may be present in pregnant women with Systemic Lupus Erithematosus. Hydroxychloroquine should not be interrupted in order to prevent exacerbation of Systemic Lupus Erithematosus. The majority of immunosuppressive drugs such as cyclophosphamide and methotrexate, are contraindicated in pregnancy.

Anticardiolipin antibodies and recurrent spontaneous abortion in Brazilianwomen / Anticardiolipin antibodies and recurrent spontaneous abortion in Brazilianwomen

Aims: To determine the frequency of anti-cardiolipin antibodies (aCL) in women with previous history of recurrent spontaneous abortion (RSA).Methods: Medical records from pregnant women seen from April 2005 to December 2008 at the High-Risk Pregnancy Unit at the Hospital de Base from FUNFARME (Fundação Faculdade Regional de Medicina), in São José do Rio Preto, São Paulo, Brazil, were revised. Patients olderthan 18 years who had at least two spontaneous abortions and who were tested for aCL wereincluded in the study. Data on maternal age, number of miscarriages and the results of serological tests for aCL were recorded. The exact Fisher's test was used to compare the results. A p value less than 0.05 was considered significant.Results: During the study period a total of 294 pregnant women were seen, from whom 44 consecutive women fulfilled the inclusion criteria. The overall mean age was 33.8±5.4 years (range: 22 to 44; median: 34). Eighteen (40.9%) patients were reagent for aCL and 26 (59.1%) non-reagent,and the difference between their mean age was not statistically significant (reagent: 34.6±5.8 years; non reagent: 33.2±5.2 years, p=0.4001). Fourteen (77.8%) patients presented IgM aCL and six (33.2%), IgG aCL. Two patients (11%) were reagent for both IgM and IgG aCL. In the most of cases the aCL antibody titers were compatible with low risk for pregnancy morbidity. The number of abortions ranged from two to six. The average number of abortions among those reagent for aCL was 3.5±1.1 and in those non-reagent was 2.9±1.1 (p=0.0813). Conclusions: The frequency of aCL was elevated among patients with a history of RSA,especially those having higher number of fetal losses. Among women with at least two spontaneousabortions, the mean number of abortions was not significantly different between those reagent for aCL and those non reagent.

Objetivos: Avaliar a frequência de anticorpos anticardiolipina (aCL) em mulheres comhistória prévia de aborto espontâneo recorrente (AER).Métodos: No período de abril de 2005 a dezembro de 2008 foram avaliados os dados deprontuários de gestantes atendidas no Ambulatório de Gestação de Alto Risco do Hospital de Baseda Fundação Faculdade Regional de Medicina (FUNFARME), em São José do Rio Preto, SãoPaulo, Brasil. Foram incluídas neste estudo pacientes com idade acima de 18 anos que tiveram pelomenos dois abortos espontâneos e foram avaliadas para aCL. O teste exato de Fisher foi usado paracomparar os resultados. Valor de p menor que 0,05 foi considerado significante.Resultados: Um total de 294 mulheres gestantes foram avaliadas durante o período doestudo, das quais 44 atendiam aos critérios de inclusão. A média de idade foi 33,8±5,4 anos(variação: 22 a 44; mediana: 34). Dezoito pacientes (40,9%) foram reagentes para aCL e 26 (59,1%)não reagentes, e a diferença entre a média de idade não foi estatisticamente significante (reagentes:34,6±5,8 anos; não reagentes: 33,2±5,2 anos, p=0,4001). Quatorze (77,8%) pacientes apresentaramaCL IgM e seis (33,2%) aCL IgG. Duas pacientes (11%) foram reagentes para ambas as classes deaCL, IgM e IgG. Na maioria dos casos os títulos de anticorpos aCL foram compatíveis com baixorisco para morbidade na gravidez. O número de abortos variou de dois a seis. O número médio deabortos entre as reagentes para aCL foi de 3,5±1,1 e entre as não reagentes foi de 2,9±1,1(p=0,0813).Conclusões: A frequência de aCL foi alta entre as pacientes com história de AER,especialmente entre aquelas que tiveram um maior número de perdas fetais. Entre as mulheres compelo menos dois abortos espontâneos, a média do número de abortos não foi significativamentediferente entre aquelas reagentes e não reagentes para aCL.

Clinical application and standardization of antiphospholipid antibodies tests / 中华检验医学杂志

According to the consensus criteria of antiphospholipid syndrome (APS),the diagnosis of APS requires the persistent presence of antiphospholipid antibodies (aPLs),indicating the critical role of aPLs in the diagnosis of APS.During the last decade,great efforts have been made to improve the laboratory detection and standardization of aPLs testing.Unfortunately,the heterogeneous nature of aPLs,lacking of standardization in aPLs test,and significant inter-laboratory variation have hampered the clinical application of aPLs test.In this commentary,the clinical application and standardization of aPLs test are focused on,and how to establish the standardization system in aPLs test in order to improve the performance of aPLs test in clinical practice are discussed.

Clinical significance of detection for anti-M-type phospholipase A2 receptor antibody in elderly patients with membranous nephropathy / 中华老年医学杂志

Objective To detect serum level of anti-M-type phospholipase A2 receptor (PLA2R) antibody in elderly patients with idiopathic membranous nephropathy (IMN) and to explore its clinical significance in IMN disease.Methods A total of 134 patients with renal biopsy-proved glomerular diseases were enrolled in this study,including 42 elderly cases with IMN,45 non-elderly cases with IMN,19 elderly cases with minimal change nephropathy (MCN),12 elderly cases with IgA nephropathy (IgAN),8 elderly cases with hepatitis B-associated membranous nephropathy (HBV-MN) and 8 elderly cases with focal segmental glomerulosclerosis (FSGS).Western blotting was used to detect serum anti-PLA2R antibody and the correlation of anti-PLA2R antibody with laboratory parameters in elderly IMN patients was analyzed.Results The elderly and non-elderly patients with IMN showed that the positive rate of anti-PLA2R antibody was 71.4％ and 73.3％,respectively (P＞ 0.05).The positive rate of anti-PLA2R antibody in elderly IgA nephropathy,HBV-MN and MCN patients was 16.7 ％,12.5％ and 5.3％ respectively.Anti-PLA2R antibody was not detected in serum from elderly FSGS patients.The positive rates of serum anti-PLA2R antibody were significantly higher in both elderly and non-elderly IMN patients than in elderly patients with secondary MN and other types of glomerlonephritis (P ＜ 0.01).Furthermore,anti-PLA2R autoantibody level was positively correlated with 24-hour urine protein level and negatively correlated with the concentration of serum albumin in elderly patients with IMN (P＜0.01).Conclusions Anti-PLA2R antibody is a sensitive serological marker of IMN.Detection for anti-PLA2R antibody might be helpful for the diagnosis of both elderly and non-elderly IMN and for the monitor of IMN disease severity.

Aborto Recurrente de Etiología Autoinmune / Autoimmune Recurrent Abortion

El curso normal del embarazo implica una serie de cambios inmunológicos que permiten el desarrollo armónico fetal. En mujeres con pérdida recurrente de la gestación, diversas etiologías se han relacionado como desencadenantes de dichas pérdidas; jugando el factor autoinmune un papel cada vez más importante. En el presente artículo, a partir de una búsqueda sistemática de información, se exponen en detalle los aspectos inmunológicos del embarazo normal, así como las alteraciones que a este nivel se presentan en mujeres con aborto recurrente. Además, se realiza una orientación diagnóstica y se exponen las diversas opciones terapéuticas utilizadas, haciendo énfasis en la necesidad de establecer protocolos estandarizados para el manejo de esta entidad.

Normal development of the pregnancy involves a number of immunological changes that allow harmonic fetal development. In women with recurrent pregnancy loss several etiologies have been implicated as triggers of such losses; autoimmune factor is nowadays playing an increasingly more important roll. In this article, based on a systematic search of information, are exposed in details the immunological aspects of normal pregnancy, as well as the immune alterations that occur in women with recurrent abortion. In addition, a diagnostic guidance is made and the various therapeutic options used are pointed out, emphasizing the need to establish standardized protocols for the management of this entity.

Anticorpos antifosfolipídeos em pacientes gravemente enfermos / Antiphospholipid antibodies in critically ill patients

Os anticorpos antifosfolipídeos são responsáveis por um amplo espectro de manifestações clínicas. A trombose venosa, arterial e microvascular, e casos graves e catastróficos são responsáveis por importante morbidade/mortalidade. Por meio da conexão dos sistemas imune, inflamatório e hemostático, é possível que esses anticorpos contribuam para o desenvolvimento de disfunções orgânicas e sejam associados com um pior prognóstico, tanto em curto quanto em longo prazos, em pacientes gravemente enfermos. Realizamos uma pesquisa do período entre janeiro de 2000 e fevereiro de 2013, utilizando a base de dados PubMed/MedLine, para avaliar a frequência de anticorpos antifosfolipídeos em pacientes gravemente enfermos e seu impacto nos desfechos desses pacientes. Encontramos apenas oito estudos originais envolvendo pacientes gravemente enfermos. Contudo, o desenvolvimento de anticorpos antifosfolipídeos parece ser frequente em pacientes gravemente enfermos, sendo porém necessários mais estudos para esclarecer seu papel patogênico e suas implicações na prática clínica.

Antiphospholipid antibodies are responsible for a wide spectrum of clinical manifestations. Venous, arterial and microvascular thrombosis and severe catastrophic cases account for a large morbidly/mortality. Through the connection between the immune, inflammatory and hemostatic systems, it is possible that these antibodies may contribute to the development of organ dysfunction and are associated with poor short and long-term prognoses in critically ill patients. We performed a search of the PubMed/MedLine database for articles written during the period from January 2000 to February 2013 to evaluate the frequency of antiphospholipid antibodies in critically ill patients and their impact on the outcomes of these patients. Only eight original studies involving critically ill patients were found. However, the development of antiphospholipid antibodies in critically ill patients seems to be frequent, but more studies are necessary to clarify their pathogenic role and implications for clinical practice.

Anticorpos antifosfolípides em adultos com púrpura trombocitopênica imune / Assessment of antiphospholipid antibodies in adult patients with immune thrombocytopenic purpura

Introdução: a púrpura trombocitopênica imune (PTI) é doença autoimune adquirida, caracterizada por trombocitopenia. A PTI em adultos usualmente apresenta evolução crônica e o diagnóstico é sugerido pela exclusão de outras causas de trombocitopenia. Anticorpos antifosfolípides (AAF) com perda fetal ou trombose vascular definem a síndrome antifosfolípide (SAF). AAFs também podem ser identificados em portadores adultos de PTI. O objetivo deste estudo foi avaliar as associações entre AAF e PTI e entre PTI AAF positivo e TV. Método: trata-se de estudo de coorte incluindo pacientes com PTI atendidos em um ambulatório de um hospital público em Belo Horizonte, entre 1981 e 2006. Os dados relativos ao diagnóstico e ao acompanhamento foram extraídos de prontuários médicos, de laudos laboratoriais e por pesquisa telefônica. Resultados: foram diagnosticados 65 adultos com PTI, dos quais 28 (43,1%) foram avaliados para AAF. Cinco pacientes foram AAF positivo (18% dos pacientes avaliados, intervalo de confiança de 95% - 7,3% a 33,9%). Não houve diferença entre os grupos AAF positivo e AAF negativo em relação à idade e evolução clínica. Houve tendência ao predomínio de pacientes masculinos no grupo AAF positivo (valor p 0,08, teste qui- -quadrado). Nenhum evento trombótico foi observado em 956 meses acumulados de observação. Conclusão: observou-se AAF em 18% dos pacientes com PTI de adultos, mas não se constatou evento trombótico em pacientes com PTI.

Introduction: Immune Thrombocytopenic Purpura (ITP) is an acquired autoimmune disease characterized by low-platelet counts. ITP in adults usually runs a chronic course and the diagnosis is suggested by ruling out other diseases that may cause thrombocytopenia. Antiphospholipid antibodies (aPL) may be associated with vascular thrombosis or fetal loss as defined by the Antiphospholipid Syndrome (APS). aPL may also be found in adul ITP. The aim of this study was to evaluate the association between aPL and ITP between aPL and venous thrombosis. Material and methods: The study is a cohort comprising adult IPT patients who attended a large public hematological unit in Belo Horizonte, Minas Gerais, from 1981 to 2006. Data on diagnosis and follow-up were abstracted from medical record, laboratory databases and by telephone interviews. Results and discussion: A total of 65 adults were identified with adult ITP of whom 28 (43,1%) had aPL tested. Five ITP patients were aPL positive (18%, 95% CI 7.3 to 33.9). There was no difference between aPL positive and negative ITP patients regarding age and clinical evolution but there was a tren towards male overrepresentation in aPL positive ITP patients (p value 0.08, chi-squared test). No venous thromboembosis was observed in 956 cumulative months of observation. Conclusion: We observed aPL in 18% of adult ITP patients but no thrombosis in adult ITP patients.

Current status and prospects of antiphospholipid antibodies tests / 中华检验医学杂志

Antiphospholipid antibodies (APLs) are important for the diagnosis of antiphospholipid syndrome (APS),especially for predicting the risk of thrombosis and pathological pregnancy.However,the heterogeneity of antiphospholipid antibodies,lacking of standardization and significant interlaboratory variation binder the clinical application of APLs and better understanding of APS diagnosis and treatment.Therefore,it is urgent to establish a standardize system for antiphospholipid antibodies test and to improve the performance of the test and perform well-designed clinical evaluation.

The evaluation of clinical value of antiphospholipid syndrome related autoantibodies / 中华检验医学杂志

Objective To evaluate the clinical application value of anti-β2 glycoprotein I ( anti-β2 GPI) and anti-cardiolipin antibodies ( ACA ) in the patients with antiphospholipid syndrome ( APS).Methods Serum levels of anti-β2GPI(IgG) and ACA(IgA, IgG, IgM) were determined by enzyme linked immunosorbent assay ( ELISA ) in 53 patients with APS , 27 patients with SLE accompanied by APS , 55 patients with simple SLE , 46 patients with other autoimmune diseases and 40 healthy controls.The sensitivity and specificity of anti-β2 GPI and ACA for the diagnosis of APS and the correlation of serum anti-β2 GPI and ACA-IgG levels were analyzed.The cases were identified in the Affiliated Hospital of Qingdao University during 2012.1 to 2014.2 and the data were analyzed with χ2 test, Mann-Whitney U test and Spearman correlation.Results The positive rates and serum levels of anti-β2 GPI, ACA-IgG/M, ACA-IgG, ACA-IgM were significantly higher in the APS group [77.4%(41/53), 81.1%(43/53), 56.6%(30/53), 52.8%(28/53);14.1 AU/ml, 19.6 U/ml, 17.9 U/ml] than those in the simple SLE group [16.4%(9/55), 32.7%(18/55), 20.0%(11/55), 18.2%(10/55); 4.9 AU/ml, 9.4 U/ml, 8.7 U/ml, χ2 =40.4, 25.7, 15.4, 14.2;U=255.0, 632.5, 476.5, P<0.01], other autoimmune diseases group[0%(0/46), 4.3%(2/46), 2.2%(1/46), 2.2%(1/46); 3.2 AU/ml, 2.6 U/ml, 3.4 U/ml, χ2 =60.7, 58.6, 33.9, 30.5;U=53.5, 87.0, 66.0, P<0.01] and healthy controls [0%(0/40), 2.5%(1/40), 0%(0/40), 2.5%(1/40);3.0 AU/ml, 3.5 U/ml, 2.9 U/ml, χ2 =55.3, 56.5, 33.4, 26.9;U=61.0, 124.0, 152.0, P <0.01 ] separately.The positive rate and serum level of ACA-IgA in the APS group [18.9%(10/53), 11.7 U/ml] were significantly higher than that in the other autoimmune disease group [2.2%(1/46), 2.9 U/ml,χ2 =6.9, U=581.0, P<0.01] and healthy controls[2.5%(1/40),2.1 U/ml,χ2 =4.4,U=764.0,P<0.05] separately.The specificity of anti-β2 GPI (83.6%) for APS diagnosis was significantly higher than that of ACA (67.3%, χ2 =4.0,P<0.05).Conclusions anti-β2 GPI, ACA-IgG and ACA-IgM, have higher clinical application value in the APS diagnosis and identification of SLE with or without APS than ACA-IgA.The specificity of anti-β2 GPI for APS diagnosis is higher than that of ACA.

A meta-analysis of correlation between antiphospholipid antibodies and retinal vein occlusion / 中华眼底病杂志

Objective To evaluate the correlation between antiphospholipid (APLA) antibodies and retinal vein occlusion (RVO).Methods A computerized search was conducted in the Pubmed,Chinese Biological Medicine Database,China National Knowledge Infrastructure,VIP database,Wanfang Database combined with manually searching of literature reference proceedings.The search time was ranged from establishment of each database to August 1st,2012.After the data extraction,quality of RCT was assessed.The meta analysis was performed by Stata 11.0.Results In total,12 case-control studies (1324subjects) that fulfilled the eligibility criteria were included in the meta-analysis involving 505 patients in RVO group and 819 subjects in control group.The odds ratio (OR) and 95％ confidence interval (CI) of APLA,anticardiolipin antibodies (ACA),lupus coagulation inhibitor and RVO were 5.01 and 3.33-7.53,4.38 and 2.38 8.05,1.72 and 0.73-4.04,respectively.The OR and 95％ CI of APLA,ACA and central RVO were 4.80 and 2.59-8.88,6.02 and 2.06-17.63,respectively.The OR and 95％ CI of APLA,ACA,lupus coagulation inhibitor and branch RVO were 4.22 and 1.67-10.63,3.69 and 1.32-10.32,2.07 and 0.79-5.41,respectively.Conclusions APLA may increase the rick of RVO,especially ACA has a prediction function to RVO.It is necessary to screening for APLA in RVO patients.

Sneddon's syndrome: case report and review of its relationship with antiphospholipid syndrome / Síndrome de Sneddon: relato de caso e revisão sobre a relação com a síndrome do anticorpo antifosfolipídio

The Sneddon's syndrome is a rare disorder characterized by the occurrence of cerebrovascular disease associated with livedo reticularis. The antiphospholipid syndrome is the most frequent type of acquired thrombophilia, defined by the occurrence of thrombosis or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. Approximately 80% of Sneddon's syndrome patients have an antiphospholipid antibody marker. These antibodies may play a pathogenetic role in some cases of Sneddon's syndrome, and many authors consider these two syndromes as the same entity. Although clinical features of antiphospholipid syndrome and Sneddon's syndrome may overlap, there is a distinction between clinical and laboratory evidence suggesting that these two entities are different diseases. A recent finding of coagulopathies, including elevated levels of coagulation factor VII, decreased levels of protein S, and activated protein C in Sneddon's syndrome patients suggested a possible biological link between the vasculopathy and a primary coagulopathy. Moreover, the clinical course seems to be progressive in Sneddon's syndrome patients and includes increase of disability and cognitive deterioration, more arterial involvement, and the antiphospholipid syndrome shows a more benign course. Both syndromes share clinical and laboratory features, and whether Sneddon's syndrome represents a spectrum of antiphospholipid syndrome remains unclear. Sneddon's syndrome patients have a worse prognosis and may represent a subgroup of patients who demands more rigorous follow-up. It is important to recognize the Sneddon's syndrome, particularly because stroke episodes may be prevented through appropriate treatment.

A síndrome de Sneddon é um distúrbio raro caracterizado pela ocorrência de doença cerebrovascular associada a livedo reticular. A síndrome do anticorpo antifosfolipídio é o tipo mais frequente de trombofilia, definida pela ocorrência de trombose ou morbidade gestacional na presença de anticorpos antifosfolípides persistentemente positivos. Aproximadamente 80% dos pacientes com síndrome de Sneddon apresentam um marcador de anticorpo antifosfolipídio. Esses anticorpos podem exercer um papel fisiopatológico em alguns casos de síndrome de Sneddon, e muitos autores consideram essa síndrome e a síndrome do anticorpo antifosfolipídio a mesma entidade. Apesar de os quadros clínicos das suas síndromes poderem se sobrepor, há evidência clínica e laboratorial distintiva, sugerindo que as duas entidades são doenças diferentes. Um achado recente de coagulopatia, incluindo níveis elevados do fator VII de coagulação, diminuição dos níveis da proteína S, e proteína C ativada em pacientes com síndrome de Sneddon, sugeriu uma possível ligação biológica entre a vasculopatia e coagulopatia primária. Além disso, o curso clínico pareceu ser progressivo em pacientes com síndrome de Sneddon, visto que há aumento de incapacidade e deterioração cognitiva, além de maior envolvimento arterial, enquanto a síndrome do anticorpo antifosfolipídio apresenta um curso mais benigno. Ambas as síndromes compartilham características clínicas e laboratoriais; até qual ponto a síndrome de Sneddon representa um espectro da síndrome do anticorpo antifosfolipídio permanece desconhecido. Os pacientes com a primeira síndrome apresentam pior prognóstico e podem representar um subgrupo de pacientes que requer um seguimento mais rigoroso. É importante reconhecer a síndrome de Sneddon já que os episódios de acidente vascular cerebral podem ser prevenidos com a terapia apropriada.