ABSTRACT
BACKGROUND: The clinical relevance of different antiphospholipid antibody (aPL) profiles, including low level anticardiolipin (aCL) and anti-ß2-glycoprotein-I (aß2GPI) antibodies, is ill-defined in the pediatric population. Our purpose is to describe the demographic, clinical, and laboratory characteristics of aPL positive pediatric patients based on different aPL profiles. FINDINGS: In this single center retrospective cohort study, based on the screening of our pediatric (age ≤ 18) rheumatology electronic medical records (2016-2022), we identified patients who had at least one "positive" aPL (lupus anticoagulant [LA], aCL IgG/M, or aß2GPI IgG/M) result. Patients were grouped into high- (LA positive and/or aCL/aß2GPI IgG/M > 40U [ELISA]) and low-risk (LA negative and aCL/aß2GPI IgG/M 20-39U) aPL profiles; those with persistently positive aPL were descriptively analyzed for demographic and clinical characteristics. Of 57 included patients, 34 (59%) had initial high- and 23 (40%) had initial low-risk profiles. Based on subsequent aPL results available in 42/57 (74%) patients, 25/27 (93%) in the high-, and 7/15 (47%) in the low-risk groups remained still positive. Of these 32 patients with persistently positive aPL, moderate-to-large vessel or microvascular thrombosis occurred in nine (28%) patients with high-risk and in none with low-risk aPL profiles; non-thrombotic aPL-related manifestations were reported in 15 (47%) patients with persistent aPL positivity. CONCLUSION: An initial high-risk aPL profile was persistent in approximately 90% of our cohort, a third of whom had thrombosis, and half had non-thrombotic aPL manifestations. Our results underscore the need for a large-scale effort to better characterize aPL-related manifestations in pediatric patients with persistent high-risk aPL-profiles.
Subject(s)
Antibodies, Anticardiolipin , Antibodies, Antiphospholipid , beta 2-Glycoprotein I , Humans , Female , Male , Child , Retrospective Studies , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Adolescent , beta 2-Glycoprotein I/immunology , Antibodies, Anticardiolipin/blood , Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/complications , Child, Preschool , Lupus Coagulation Inhibitor/blood , Lupus Coagulation Inhibitor/immunology , Rheumatic Diseases/immunology , Rheumatic Diseases/blood , Thrombosis/etiology , Thrombosis/immunology , Clinical RelevanceABSTRACT
OBJECTIVE: This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). METHODS: Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. RESULTS: There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiß2GP1) positivity had an increased risk of fetal loss. CONCLUSIONS: Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiß2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth.PROSPERO (CRD42023388122).
Subject(s)
Antibodies, Antiphospholipid , Lupus Erythematosus, Systemic , Pregnancy Complications , Pregnancy Outcome , Humans , Pregnancy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/complications , Female , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Pregnancy Complications/immunology , Pregnancy Complications/epidemiology , Antibodies, Anticardiolipin/blood , Antibodies, Anticardiolipin/immunology , Lupus Coagulation Inhibitor/blood , Lupus Coagulation Inhibitor/immunology , Risk Factors , Risk , Premature Birth/epidemiology , Premature Birth/immunology , beta 2-Glycoprotein I/immunologyABSTRACT
OBJECTIVE: To compare clinical and laboratory data obtained from patients with primary Antiphospholipid Syndrome (pAPS) with and without Thrombotic Microangiopathy (TMA). PATIENTS AND METHODS: A cross-sectional study with 66 (83.3% female) pAPS patients was performed. Demographic, clinical, drug use, antiphospholipid antibodies data were evaluated. Patients were subdivided into one of two groups: pAPS with TMA and pAPS without TMA and were compared. RESULTS: In this sample, 5/66 (7.6%) of patients had TMA. Primary APS with TMA group exhibited a higher frequency of arterial events (100% vs. 54.1%, p=0.02), stroke (100% vs. 32.8%, p=0.001) and a lower frequency of deep venous thrombosis (0 vs. 68.9%, p=0.0009) compared to the patients without TMA. Analysis of therapy used in these patients showed a higher frequency of current (40% vs. 6.6%, p=0.0006) and previous glucocorticoid use (80% vs. 36%, p=0.0007) and statin use (50% vs. 22.9%, p=0.037) in the first group. The two groups exhibited no differences in the frequency of positive autoantibodies, except for higher IgG anticardiolipin titers (86 ± 52 vs. 34.5 ± 39 GPL, p=0.003). CONCLUSIONS: Patients with pAPS and TMA have distinct clinical and laboratory spectra from those without TMA, that is characterized by an increased frequency of arterial events, stroke, and higher titers of IgG anticardiolipin; they have deep venous thrombosis less frequently.
Subject(s)
Antiphospholipid Syndrome/complications , Stroke/epidemiology , Thrombotic Microangiopathies/complications , Venous Thrombosis/epidemiology , Adult , Antibodies, Anticardiolipin/immunology , Antibodies, Antiphospholipid/immunology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Risk Factors , Stroke/etiology , Venous Thrombosis/etiologyABSTRACT
Background: Diagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China. Methods: A total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and aß2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features. Results: CLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or aß2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems. Conclusion: CLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.
Subject(s)
Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Pathology, Molecular/methods , Reagent Kits, Diagnostic , Adult , Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/diagnosis , Cohort Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Pathology, Molecular/instrumentation , Reproducibility of Results , Sensitivity and Specificity , Young Adult , beta 2-Glycoprotein I/immunologyABSTRACT
PURPOSE OF REVIEW: COVID-19 patients have a procoagulant state with a high prevalence of thrombotic events. The hypothesis of an involvement of antiphospholipid antibodies (aPL) has been suggested by several reports. Here, we reviewed 48 studies investigating aPL in COVID-19 patients. RECENT FINDINGS: Prevalence of Lupus Anticoagulant (LA) ranged from 35% to 92% in ICU patients. Anti-cardiolipin (aCL) IgG and IgM were found in up to 52% and up to 40% of patients respectively. Anti-ß2-glycoprotein I (aß2-GPI) IgG and IgM were found in up to 39% and up to 34% of patients respectively. Between 1% and 12% of patients had a triple positive aPL profile. There was a high prevalence of aß2-GPI and aCL IgA isotype. Two cohort studies found few persistent LA but more persistent solid phase assay aPL over time. aPL determination and their potential role is a real challenge for the treatment of this disease.
Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , Thrombosis/immunology , Antibodies, Anticardiolipin/immunology , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/complications , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/immunology , SARS-CoV-2 , Severity of Illness Index , Thrombosis/blood , Thrombosis/etiology , beta 2-Glycoprotein I/immunologyABSTRACT
PURPOSE OF THE REVIEW: Elevated levels of anti-phospholipid (aPL) antibodies are the most important criterion in the diagnosis of anti-phospholipid syndrome (APS) and are usually responsible for promoting the risk of thrombotic complications. Now, in the course of the global coronavirus disease 2019 (COVID-19) pandemic, measurable aPL antibodies have also been detected in a noticeable number of patients showing a variety ranging from studies with only isolated positive tests to cohorts with very high positivity. Thus, the question arises as to whether these two different clinical pictures may be linked. RECENT FINDINGS: The ambivalent results showed a frequent occurrence of the investigated aPL antibodies in COVID-19 patients to an individually varying degree. While some question a substantial correlation according to their results, a number of studies raise questions about the significance of a correlation of aPL antibodies in COVID-19 patients. Within the scope of this review, these have now been described and compared with each other. Ultimately, it is necessary to conduct further studies that specifically test aPL antibodies in a larger context in order to make subsequent important statements about the role of APS in COVID-19 and to further strengthen the significance of the described comparisons.
Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , Antibodies, Anticardiolipin/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/immunology , SARS-CoV-2 , beta 2-Glycoprotein I/immunologyABSTRACT
BACKGROUND: Systemic lupus erythematosus (SLE) may have a different serological and clinical profile according to age of disease onset. AIM: To compare clinical presentation and serological data from patients with SLE onset in childhood (cSLE) with disease onset in adulthood (aSLE) in a sample of Brazilian patients. METHODS: Retrospective study of 614 SLE patients from a single Rheumatology Unit from Brazil: 77 (12.5%) cSLE and 537 (87.4%) aSLE. Clinical and serological data were obtained from the charts. Comparisons of cSLE with aSLE in general and according to patient's gender were made. RESULTS: The comparison of whole sample showed that children had more malar rash (p = 0.04), seizures (p < 0.0001), psychosis (p = 0.02), glomerulonephritis (p = 0.001), anti-dsDNA (p = 0.008), anticardiolipin IgM (p = 0.04) but less discoid lesions (p = 0.01), anti-Ro (p < 0.0001) and anti-La antibodies (p = 0.007). When only the male sample was compared, no differences in glomerulonephritis and anti-dsDNA frequencies were found. CONCLUSION: Children had a higher frequency of severe manifestations (glomerulonephritis and central nervous system) than adults. The difference in glomerulonephritis occurrence disappeared when only males were compared.
Subject(s)
Antibodies, Anticardiolipin/immunology , Antibodies, Antinuclear/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Adolescent , Adult , Age of Onset , Brazil/epidemiology , Case-Control Studies , Child , Exanthema/diagnosis , Exanthema/epidemiology , Female , Glomerulonephritis/diagnosis , Glomerulonephritis/epidemiology , Humans , Immunoglobulin M/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Male , Prevalence , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Retrospective Studies , Seizures/diagnosis , Seizures/epidemiology , Severity of Illness IndexABSTRACT
BACKGROUND: Reports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking. METHODS: 22 COVID-19+ and 20 COVID-19- patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anticardiolipin (aCL), anti-ß2glycoprotien 1 (ß2GP1), antidomain 1 ß2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance was used for continuous variables and Fisher's exact test was used for categorical variables with α=0.05 and the false discovery rate at q=0.05. RESULTS: APLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19+. CONCLUSIONS: Positive APLA serology was associated with more severe disease regardless of COVID-19 status. TRIAL REGISTRATION NUMBER: NCT04747782.
Subject(s)
Antibodies, Anticardiolipin/immunology , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , COVID-19/immunology , Aged , Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , COVID-19/blood , COVID-19/complications , Critical Illness , Female , Humans , Male , Middle Aged , SARS-CoV-2ABSTRACT
BACKGROUND: The relationship between anticardiolipin (aCL) antibodies and cardiovascular events is uncertain and may vary according to arterial location. MATERIALS AND METHODS: FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral artery disease (PAD). The rate of subsequent ischaemic events was cross-referenced with the presence of aCL antibodies (any isotype, IgG or IgM). RESULTS: As of June 2017, 1387 stable outpatients were recruited. Of these, 120 (8.7%) showed positive levels of aCL antibodies. Over an average follow-up of 18 months, 250 patients developed subsequent events: 101 myocardial infarction, 57 ischaemic stroke and 92 critical leg events. Patients with positive aCL antibodies had a higher risk of distal artery events (a composite of ischaemic stroke or critical leg events) than patients with undetectable or low levels (rate ratio: 1.66; 95% CI: 1.07-2.60). However, an association with central coronary events was not found. The multivariate Cox analysis after adjustment for relevant clinical covariates showed that positivity of aCL antibodies is an independent risk factor for distal events (hazard ratio: 1.60; 95% CI: 1.01-2.55; P < .05). CONCLUSIONS: Positivity of aCL antibodies is associated with an increased risk of subsequent distal artery ischaemic events (cerebral or leg arteries) but not coronary artery events. Anticardiolipin antibodies appear to have a different relationship on the localisation of ischaemic events in patients with symptomatic artery disease.
Subject(s)
Antibodies, Anticardiolipin/immunology , Cerebrovascular Disorders/immunology , Coronary Artery Disease/immunology , Ischemic Stroke/immunology , Myocardial Infarction/immunology , Peripheral Arterial Disease/immunology , Aged , Female , Humans , Ischemia/epidemiology , Ischemia/immunology , Ischemic Stroke/epidemiology , Lower Extremity/blood supply , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/epidemiology , Proportional Hazards Models , Recurrence , RegistriesABSTRACT
Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced against a variety of phospholipids and phospholipid-binding proteins. The purpose of this article is to review cutaneous findings in patients with APS diagnosis. An overview regarding prevalence, description, pathogenesis and histopathology, are described for cutaneous manifestations of APS.
Subject(s)
Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/pathology , Livedo Reticularis/pathology , Skin Diseases/pathology , Vasculitis/pathology , Adult , Aged , Anetoderma/etiology , Anetoderma/pathology , Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/epidemiology , Antiphospholipid Syndrome/immunology , Biopsy , Female , Gangrene/etiology , Gangrene/pathology , Humans , Livedo Reticularis/diagnosis , Livedo Reticularis/etiology , Livedo Reticularis/immunology , Lupus Coagulation Inhibitor/immunology , Male , Malignant Atrophic Papulosis/etiology , Malignant Atrophic Papulosis/pathology , Middle Aged , Necrosis/diagnosis , Necrosis/etiology , Prevalence , Skin Diseases/immunology , Ulcer/pathology , Vasculitis/etiologyABSTRACT
OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.
Subject(s)
Antiphospholipid Syndrome/epidemiology , Ischemic Stroke/epidemiology , Adult , Antibodies, Anticardiolipin/immunology , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Antiphospholipid Syndrome/immunology , Case-Control Studies , Diabetes Mellitus/epidemiology , Female , Functional Status , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , International Normalized Ratio , Ischemic Stroke/etiology , Ischemic Stroke/immunology , Ischemic Stroke/physiopathology , Lupus Coagulation Inhibitor/immunology , Male , Mesenteric Ischemia/epidemiology , Mesenteric Ischemia/etiology , Mesenteric Vascular Occlusion/epidemiology , Mesenteric Vascular Occlusion/etiology , Middle Aged , Portal Vein , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Risk Factors , Venous Thrombosis/epidemiology , Venous Thrombosis/etiologyABSTRACT
RATIONALE: Idiopathic hypertrophic pachymeningitis (IHP) is a rare neurological disorder without a definite etiology. Diagnosis is mainly based on exclusion of other etiologies. PATIENT CONCERNS: A 41-year-old male patient presented with insidious onset headache of 3-month duration. DIAGNOSES: Contrast-enhanced brain magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement over bilateral cerebral hemispheres and the tentorium cerebelli. Lumbar puncture showed increased pressure, lymphocytic pleocytosis, and elevated protein level with normal glucose concentration. Blood tests detected elevated erythrocyte sedimentation rate (ESR) and C-reactive protein. Pathological examination of the dura mater from the right frontal convexity disclosed coarse collagenous deposition with focal lymphoid aggregation. After malignancy and infectious etiologies were excluded, a diagnosis of IHP was made. INTERVENTIONS: Oral prednisolone and azathioprine followed by methotrexate were administered. OUTCOMES: During the 7-year follow-up period, although the patient was not totally headache-free, medical therapy significantly reduced the severity of headache. Follow-up MRI studies showed a reduction in meningeal enhancement and serial ESR measurements revealed a trend of improvement. LESSONS: Methotrexate therapy may be considered in cases of steroid-resistant IHP. In addition to clinical evaluation, serial ESR testing may be considered to guide the treatment strategy and assess the response to therapy.
Subject(s)
Antibodies, Anticardiolipin/immunology , Headache/immunology , Hypertrophy/immunology , Meningitis/immunology , Adult , Brain/immunology , Brain/pathology , Dura Mater/immunology , Dura Mater/pathology , Humans , MaleSubject(s)
Antibodies, Anticardiolipin/blood , COVID-19/complications , Chilblains/etiology , Immunoglobulin A/blood , Pandemics , SARS-CoV-2 , Adolescent , Adult , Antibodies, Anticardiolipin/immunology , Antibody Specificity , Autoantigens/immunology , COVID-19/immunology , Cell-Derived Microparticles/immunology , Chilblains/blood , Chilblains/immunology , Child , Child, Preschool , Complement C3/deficiency , Convalescence , Humans , Immunoglobulin A/immunology , Membrane Lipids/immunology , Phospholipids/immunology , Retrospective Studies , SARS-CoV-2/physiology , Time Factors , Young AdultSubject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antiphospholipid Syndrome/drug therapy , Complement Inactivating Agents/therapeutic use , Multiple Organ Failure/therapy , Antibodies, Anticardiolipin/immunology , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/genetics , Antiphospholipid Syndrome/immunology , Blood Proteins/genetics , Brachiocephalic Veins/diagnostic imaging , Bronchiolitis, Viral/complications , Complement C3b Inactivator Proteins/genetics , Computed Tomography Angiography , Continuous Renal Replacement Therapy , Evoked Potentials, Visual , Humans , Infant , Intensive Care Units, Pediatric , Jugular Veins/diagnostic imaging , Male , Multiple Organ Failure/etiology , Plasma Exchange , Respiratory Syncytial Virus Infections/complications , Sequence Deletion , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/blood , Thrombocytopenia/drug therapy , Thrombocytopenia/etiology , Thrombophilia/blood , Thrombophilia/etiology , Thrombophilia/therapy , Vasoconstrictor Agents/therapeutic use , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Water-Electrolyte Imbalance/etiologyABSTRACT
We report a patient with severe Covid-19-associated coagulopathy and type 2 diabetes mellitus who tested positive for antiphospholipid antibodies (aPL). Analysis of skin specimens suggested direct SARS-CoV-2 viral-induced and complement-mediated vascular injury and thrombosis, consistent with prior reports. Serial aPL testing demonstrated high levels of anticardiolipin antibodies (aCL) that declined to insignificant levels over a period of 5 weeks. SARS-CoV-2 RNA was detected in nasopharyngeal swab specimens on serial assays performed over the same 5-week period, though it was not detected thereafter. We hypothesize that SARS-CoV-2 viral-induced aPL contributed to severe Covid-19-associated coagulopathy in this patient.
Subject(s)
COVID-19/virology , Diabetes Mellitus, Type 2/complications , SARS-CoV-2/pathogenicity , Thrombosis/etiology , Antibodies, Anticardiolipin/immunology , COVID-19/complications , COVID-19/diagnosis , Diabetes Mellitus, Type 2/virology , Female , Humans , Middle AgedSubject(s)
Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/diagnosis , COVID-19/immunology , Thrombophilia/immunology , Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/immunology , COVID-19/blood , Humans , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/immunology , SARS-CoV-2 , Thrombophilia/blood , Thrombosis/blood , Thrombosis/immunology , beta 2-Glycoprotein I/immunologyABSTRACT
OBJECTIVE: We evaluated which aPL combinations increase the risk of future thrombosis in patients with SLE. METHODS: This prospective cohort study consisted of SLE patients who had been tested for all seven aPL (LA, aCL isotypes IgM, IgG and IgA, and anti-ß2-glycoprotein I isotypes IgM, IgG and IgA). Pooled logistic regression was used to assess the relationship between aPL and thrombosis. RESULTS: There were 821 SLE patients with a total of 75 048 person-months of follow-up. During the follow-up we observed 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous and 3 with both arterial and venous thrombosis. In individual models, LA was the most predictive of any [age-adjusted rate ratio 3.56 (95% CI 2.01, 6.30), P < 0.0001], venous [4.89 (2.25, 10.64), P < 0.0001] and arterial [3.14 (1.41, 6.97), P = 0.005] thrombosis. Anti-ß2-glycoprotein I IgA positivity was a significant risk factor for any [2.00 (1.22, 3.3), P = 0.0065] and venous [2.8 (1.42, 5.51), P = 0.0029] thrombosis. Only anti-ß2-glycoprotein I IgA appeared to add significant risk to any [1.73 (1.04, 2.88), P = 0.0362] and venous [2.27 (1.13, 4.59), P = 0.0218] thrombosis among those with LA. We created an interaction model with four categories based on combinations of LA and other aPL to look at the relationships between combinations and the risk of thrombosis. In this model LA remained the best predictor of thrombosis. CONCLUSION: Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-ß2-glycoprotein I IgA.
Subject(s)
Antibodies, Anticardiolipin/immunology , Lupus Coagulation Inhibitor/immunology , Lupus Erythematosus, Systemic/immunology , Thrombosis/immunology , beta 2-Glycoprotein I/immunology , Adult , Antibodies, Antiphospholipid/immunology , Cohort Studies , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Ischemia/epidemiology , Ischemia/immunology , Logistic Models , Male , Myocardial Infarction/epidemiology , Myocardial Infarction/immunology , Prospective Studies , Pulmonary Embolism/epidemiology , Pulmonary Embolism/immunology , Risk Factors , Stroke/epidemiology , Stroke/immunology , Thrombosis/epidemiology , Venous Thrombosis/epidemiology , Venous Thrombosis/immunologyABSTRACT
Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-ß2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-ß2GPI antibodies was not reported. Objective: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-ß2GPI antibodies. Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. Results: Anti-ß2GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of ß2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-ß2GPI nor with thrombosis. Conclusions: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against ß2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.
Subject(s)
Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/immunology , COVID-19/immunology , SARS-CoV-2 , Aged , Aged, 80 and over , Antibodies, Anticardiolipin/blood , Antiphospholipid Syndrome/blood , COVID-19/blood , COVID-19/virology , Critical Illness , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Luminescent Measurements , Male , Middle Aged , Phosphatidylserines/immunology , Prothrombin/immunology , Thrombosis/immunology , beta 2-Glycoprotein I/immunologyABSTRACT
BACKGROUND: Small case-series have reported overt myocardial dysfunction to be associated with positive antiphospholipid antibodies in patients of systemic lupus erythematosus (SLE). However, there is no case-control study that has examined this association. METHODS: This case-control study recruited patients of SLE (fulfilling SLICC criteria) with overt myocardial dysfunction as cases and those without this as controls. Overt myocardial dysfunction was defined by echocardiography as global left ventricular dysfunction and reduced ejection fraction (<50%). Those patients with a prior diagnosis of anti-phospholipid antibody syndrome, coronary artery disease, rheumatic heart disease or severe pulmonary artery hypertension were excluded. Antibodies tested included lupus anticoagulant, anticardiolipin antibodies (IgM and IgG) and anti-beta 2 glycoprotein 1 antibodies (IgM and IgG). Patients with positive tests underwent repeat testing for persistent positivity after 12 weeks. RESULTS: This study included 51 patients (21 cases and 30 controls) having a mean (SD) age of 33 (13.3) years, and disease duration (median, IQR) of 28 months (12-38 months). The mean ejection fraction of cases was 31.7 (9.3)% while that of controls was 55.7 (1.7)% (p = 0.03). The frequency (percentage) of positive antiphospholipid antibodies was not significantly different between cases and controls (43%, 40%, p = 0.8). The frequency (percentage) of anti-cardiolipin antibody was also not significant between the groups (38%, 37%, p = 0.57). Serositis and leucopenia were more prevalent in SLE patients with myocardial dysfunction (p = 0.005). CONCLUSION: This study did not find any significant association of anti-phospholipid antibodies with overt myocardial dysfunction in patients of SLE.
Subject(s)
Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/blood , Cardiomyopathies/diagnostic imaging , Lupus Coagulation Inhibitor/blood , Lupus Erythematosus, Systemic/blood , Adult , Antibodies, Anticardiolipin/immunology , Antibodies, Antiphospholipid/immunology , Case-Control Studies , Cross-Sectional Studies , Echocardiography , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Prevalence , Young Adult , beta 2-Glycoprotein I/immunologyABSTRACT
BACKGROUND: High incidence of thrombosis in COVID-19 patients indicates a hypercoagulable state. Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest. OBJECTIVES: To illustrate the incidence of criteria (lupus anticoagulant [LAC], anticardiolipin [aCL] immunoglobulin G [IgG]/IgM, antibeta2-glycoprotein I antibodies [aß2GPI] IgG/IgM) and noncriteria (anti-phosphatidyl serine/prothrombin [aPS/PT], aCL, and aß2GPI IgA) aPL in a consecutive cohort of critically ill SARS-CoV-2 patients, their association with thrombosis, antibody profile and titers of aPL. PATIENTS/METHODS: Thirty-one consecutive confirmed COVID-19 patients admitted to the intensive care unit were included. aPL were measured at one time point, with part of the aPL-positive patients retested after 1 month. RESULTS: Sixteen patients were single LAC-positive, two triple-positive, one double-positive, one single aCL, and three aCL IgG and LAC positive. Seven of nine thrombotic patients had at least one aPL. Sixteen of 22 patients without thrombosis were aPL positive, amongst them two triple positives. Nine of 10 retested LAC-positive patients were negative on a second occasion, as well as the double-positive patient. Seven patients were aPS/PT-positive associated to LAC. Three patients were aCL and aß2GPI IgA-positive. CONCLUSION: Our observations support the frequent single LAC positivity during (acute phase) observed in COVID-19 infection; however, not clearly related to thrombotic complications. Triple aPL positivity and high aCL/aß2GPI titers are rare. Repeat testing suggests aPL to be mostly transient. Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID-19 patients.