Anti-cardiolipin antibody English name: anticardiolipin antibody; ACA Definition: a group of autoantibodies against various negatively charged phospholipids. They include anti-cardiolipin, anti-phosphatidylserine, anti-phosphatidylglycerol, anti-phosphatidic acid and other antibodies, which can be used as one of the diagnostic indicators of antiphospholipid antibody syndromes (including thrombosis, spontaneous abortion, thrombocytopenia and central nervous system lesions).
Applied disciplines.
Immunology (primary discipline);
Immune system (secondary subject);
Anticardiolipin (ACA) is an autoantibody that uses negatively charged cardiolipin on platelets and endothelial cell membranes as a target antigen. It is commonly found in systemic lupus erythematosus (SLE) and other autoimmune diseases. The antibody is closely associated with thrombosis, platelets, spontaneous abortion, or intrauterine stillbirth. Since Harris et al. established a method for measuring ACA in 1983, research on this antibody has gained widespread attention and developed rapidly worldwide.
I. Clinical manifestations of antiphospholipid syndrome
1.Thrombosis
2.Fetal pregnancy loss
3.The mechanism of fetal death caused by ACA
4.Thrombocytopenia
5.Other clinical manifestations
6.The mechanism of ACA causing neurological pathology guidelines
II. Diagnosis of antiphospholipid syndrome
1.Clinical manifestations
2.Laboratory indicators
3.Diagnostic conditions
Antiphospholipid syndrome treatment principles
Treatment of antiphospholipid syndrome in pregnancy.
1.Aspirin
2.Prednisone
3.Heparin
4.Immunoglobulin
Anti-cardiolipin antibodies and hepatitis B infection
1. Anti-cardiolipin antibodies and hepatitis B infection
ACA is one of the components of anti-phospholipid antibodies (anti-phospholipikantibodies, APA), a group of antibodies that can react with a variety of antigenic substances containing phospholipid structures, including lupus anticoagulant (LA), anti-phosphatidic acid anti (anti- phosphatidicacidantibody) and anti-phosphatidylserineantibody.
ACA is bound to the negatively charged phosphodiester group in the cardiolipin molecule, but this binding requires the glycerol ester portion of the cardiolipin molecule. The fatty acid portion of the ACA molecule is essential for its antigenicity; ACA does not bind to the loaded phosphodiester group in other molecules, but reacts only with this component of the phospholipid molecule.
In recent years, Hotkko et al. found that ACA binds only to oxidized cardiolipin, but not to oxidized reduced cardiolipin analogs, and Koike suggested that binding of cardiolipin to IgG of ACA requires the presence of ACA cofactor β2-glycoprotein I (β2-GPI). The method is considered to be highly sensitive for the complex of cardiolipin and β2-GPI, and was later modified by Loizou et al. into a more convenient ELISA method with the same effect as the radioimmunoassay. Because of the high sensitivity of the method, the quantitative, detectable antibody classes and subclasses, and easy standardization, it has become a worldwide standard for the quantitative determination of ACA. immunological typing of ACA has three categories, IgG and IgA and IgM, and there is no significant difference in the incidence of ACA between men and women.
Studies have confirmed that many factors are closely related to ACA production, and common causes include.
(1) Autoimmune diseases: such as systemic lupus erythematosus (SLE), scleroderma of rheumatoid arthritis (RA), etc. ;
(2) Viral infections: such as adenovirus, rubella virus, varicella virus, mumps virus and other infections;
(3) Other diseases: such as mycoplasma systemic diseases, etc.;
(4) Oral administration of certain drugs: such as chlorpromazine, phenothiazine, etc;
(5) A few normal people without obvious organic diseases, especially the elderly.
Anti-phospholipid syndrome (APS) is a general term for a group of clinical signs caused by anti-phospholipid antibodies (APL antibodies), mainly manifesting as thrombosis, habitual abortion and thrombocytopenia. APS is an autoimmune disease and the accepted diagnostic criteria are that the patient has one of the following clinical features: recurrent miscarriage; fetal death and neonatal death due to early delivery in intrauterine distress; autoimmune thrombocytopenia.
These clinical manifestations are accompanied by the presence of APL including anti-cardiolipin antibodies (ACA) and lupus coagulation factors (LA) in the patient’s serum. In clinical practice, it is also called anti-cardiolipin syndrome (ACS) because the anti-cardiolipin antibodies are more specific and more closely related to the above clinical manifestations.
APL is a group of specific autoantibodies against phospholipid negatively charged protein complexes in the body. Some plasma proteins in the body, such as β2-glycoprotein (β2-GPI), have antigenic determinants of ACA on their molecules. GPI has the ability to inhibit platelet aggregation caused by thrombinogen, adenosine diphosphate (ADP), and thrombin generation on its surface, and to block phospholipid-dependent coagulation reactions, which predispose to thrombus formation when ACA reacts with it. Therefore, when ACL binds to cells and induces procoagulant activity through protein-bound phospholipids, phospholipids play a role in the mechanism of APS embolism, and when this syndrome occurs in systemic lupus erythematosus (SLE), it is referred to as secondary antiphospholipid syndrome, while in non-SLE patients it is referred to as primary phospholipid syndrome.
Clinical manifestations of antiphospholipid syndrome
1. Thrombosis
The most prominent manifestation of the antiphospholipid syndrome is thrombosis, which can occur in arteries or veins. The most common of these are recurrent deep vein thrombosis, including renal, retinal, and inferior vena cava thrombosis, but the greater threat to patients is arterial thrombosis. Histopathology in ACA-positive SLE patients reveals non-inflammatory obstructive vascular lesions that are segmental in nature, with few but severe lesions. There was fibrous thrombosis in the intracardiac arteries and caused myocardial infarction, and capillaries and small arteries were obstructed by fibrous material; all of these pathological changes were likely the result of APL antibody action. It is believed that the possible mechanisms of thrombosis caused by ACA are: ACA reacts with platelets or membrane phospholipids of vascular endothelial cells with antigen and antibody and inhibits the synthesis of prostacyclin (PG12) by vascular endothelial cells, thus increasing the factors of thrombosis; ACA damages vascular endothelial cells, causing them to release less fibrinogenic substances and reduce fibrinolytic activity, thus increasing the tendency of thrombosis; ACA- IgG also causes direct immune damage to endothelial cells, which triggers platelet adhesion, aggregation, and factor Ⅻ activation; ACA inhibits thrombomodulin, which reduces activated protein C and increases coagulation activity in vivo, contributing to thrombosis. Approximately 1/3 of pregnancies with combined APS are asymptomatic, 1/3 of patients are considered to have systemic lupus erythematosus (SLE), and 1/3 present with recurrent miscarriage, stillbirth, preterm delivery, or IUGR. The incidence of recurrent miscarriage and intrauterine death in LA-positive untreated cases is over 90%; the incidence of stillbirth in CA-positive patients is about 76%; IUGR accounts for 60% of the live infants delivered with APS. Pregnancy with APS has an increased chance of preeclampsia, and the rate of positive APA in patients with preeclampsia is significantly higher than in normal pregnancies. One case of APS with recurrent miscarriage and a second delivery of a malformed child with renal atrophy and oral-maxillary hypoplasia has been reported, suggesting that APS pregnancy has the potential to cause congenital malformations.
2. Fetal pregnancy loss
ACA-positive women are more likely to have recurrent miscarriages in early pregnancy and intrauterine fetal death in mid- and late pregnancy, especially those with moderate to highly elevated ACA-IgG levels. The occurrence of intrauterine fetal death is a more characteristic type of miscarriage than early pregnancy. The study by Lockshin et al. revealed that ACA predicted spontaneous miscarriage earlier and more sensitively.
3. The mechanism of fetal death caused by ACA
may be.
(1) ACA can cause a decrease in PG12 level in the myometrium, making the placenta prone to infarction and leading to miscarriage.
(2) ACA causes placental vasculitis, resulting in fetal death due to insufficient oxygen supply and nutrition.
(3) ACA acts on placental thrombosis and vasoconstriction, reducing placental blood flow, resulting in fetal distress and death.
4.Thrombocytopenia
APL is an antibody that directly targets the cell membrane and can cause autoimmune hemolytic anemia. 30% of patients with idiopathic thrombocytopenic purpura are reported to be positive for APL, which binds to platelet membrane phospholipids and activates platelets and accelerates their aggregation, resulting in thrombocytopenia. ACA binds to platelet phospholipids and increases platelet phagocytosis and destruction by the mononuclear macrophage system, leading to thrombocytopenia; ACA promotes platelet activation, which leads to easy formation of thrombus, while platelet consumption decreases.
5.Other clinical manifestations
Reticular cyanosis is the most common cutaneous manifestation of APS and is seen in about 80% of patients. Non-stroke neurological manifestations are often caused by small vessel embolic disease and can be psychiatric disorders or transient ischemic attacks. Recent literature reports that ACA is associated with neuropsychiatric disorders, and those with positive ACA in central nervous system lesions can manifest as epilepsy, migraine, temporary cerebral ischemia and transient blackouts, psychiatric abnormalities, hemiparesis, cerebral infarction, stroke, etc. Some non-embolic neurological diseases such as chorea, Guillain-Barre syndrome are also associated with ACA.
6, ACA to the mechanism of neurological pathology guidelines
(1) Microinfarct foci are formed in brain tissue due to thrombosis, and in a few cases, large infarcts in brain tissue due to large artery embolism cause hemiparesis.
(2) It is possible that ACA cross-reacts with phospholipids of nerve cells, thus causing neurological damage. (3) Neuropathy in SLE patients may be related to the disruption of the blood-brain barrier caused by the inhibition of glial cells by ACA and the action of ACA on nerve cells and nerve fibers.
Diagnosis of antiphospholipid syndrome
1. Clinical manifestations
(1) venous thrombosis
(2) Arterial thrombosis
(3) Habitual abortion
(4)Thrombocytopenia
2.Laboratory indexes
(1)IgG-APL (medium/high level)
(2)IgM-APL
(3)Positive LA
3.Diagnostic conditions
(1)Meet 1 clinical manifestation index plus 1 laboratory index
(2)APL positive for two times with interval >3 months
(3) Follow up for more than 5 years to exclude SLE or other autoimmune diseases.
Principles of antiphospholipid syndrome treatment.
1.Anti-platelet aggregation drugs: aspirin
2.Anticoagulation therapy; Warfarin and heparin
3.Promoting fibrinogenic chain kinase
The relationship between anti-cardiolipin antibodies and intrauterine fetal growth retardation of unknown origin Pregnancy combined with antiphospholipid syndrome (ADS) often causes pregnancy loss, intrauterine fetal growth retardation, and gestational hypertension syndrome, and its mechanism of occurrence has been controversial. It is now believed that thrombosis induced by antiphospholipid antibodies produced in vivo is the main factor in pregnancy failure, as is the formation of placental thrombosis. Combined APS in pregnancy often causes severe maternal pregnancy complications, such as gestational hypertensive syndrome, recurrent miscarriage, intrauterine death, preterm delivery, IUGR and other poor fetal prognosis. These manifestations are associated with pathophysiological changes in the placenta, which can be secondary to placental dysplasia and placental insufficiency when the pregnancy is affected by APS.
The pathological histological changes of the placenta caused by APS include, abnormal uteroplacental vascular exchange, defective placental formation, and chronic inflammation of the placenta, which is associated with placental vascular embolism. Deposition of fibrin-like material on the surface of the villi trophectoderm was found in all placental tissues with APS and increased with gestational age, which can lead to partial to complete obstruction of the uteroplacental vasculature. Blurring of the spiral vascular structure, increased eosinophilia, fibrinoid necrosis and atherosclerosis of the canal wall can be found at the uteroplacental vasculature, and due to damage of these vessels can cause premature placental abruption, chorionic infarction, and terminal chorionic fibrosis. Fibrin deposition, wall thickening and even luminal obstruction of the placenta’s internal villi can also occur, resulting in capillary obstruction and even the appearance of a thick cell-free eosinophilic stroma, leading to decreased placental exchange function.
Research data suggest that cell irritation, endocrine dysfunction and even cell death due to uteroplacental hypoperfusion caused by uteroplacental vascular embolism can lead to premature rupture of membranes or preterm delivery, and the deposition of immune complexes formed by APA, tissue damage caused by tissue ischemia or hypoperfusion can induce coagulation and thus aggravate embolism. Placental proteins are particularly sensitive to ACA because some anticoagulant placental proteins are associated with phospholipids in the trophoblast membrane, and ASA may also affect the growth and maturation of the chorionic trophoblast by reducing the fusion of syncytial cells. The cytotoxicity of antibodies to trophoblast and phospholipids has been demonstrated in chronic inflammatory tissue of the villi in IUGR, and anti-trophoblast antibodies have been found in patients with intrauterine fetal death due to APS. ACA can cause congenital malformation or death of the fetus by exposure to embryonic vascular endothelial cells.
The target organs damaged by ACA include the placenta, fetus and uterine wall, causing extensive placental infarction, chorionic villus aging, and fibrinoid necrosis of the uterine placental vessels. The pathological histological changes of the placenta may be similar in each pregnancy in women with combined APS without treatment, and if the first pregnancy fails due to interstitial chorioamnionitis, the next pregnancy will fail for the same reason of interstitial chorioamnionitis. In the prediction of adverse pregnancy outcomes, routine screening of pregnant women for ACA in early pregnancy is more beneficial than selective screening. yasuda et al, by screening 860 pregnant women for ACA in early pregnancy by ELISA, the ACA positive rate was 7.0% and the negative rate was 93%. In the ACA-positive group, the incidence of IUGR was 11.7%; significantly higher than the 1.9% in the negative group