IgM Anticardiolipin Antibodies Research Articles

Recurrent miscarriage and low-titer antiphospholipid antibodies

ObjectiveTo evaluate the clinical features and pregnancy outcomes in patients experiencing recurrent miscarriage (RM) with either low-titer or medium-high titer positivity of antiphospholipid antibodies (aPL).MethodsA retrospective review of medical records was conducted for patients with aPL positivity and recurrent miscarriage between 2018 and 2022. The clinical features, treatment strategies, outcomes were compared between the patients with low (n = 92) and medium (n = 32) titer of aPL.ResultsA total of 118 patients, resulting in 124 obstetric episodes (pregnancies), with a mean age of 33. 15 ± 4.56 and 31.47 ± 4.41 years between the two groups. The low-titer group exhibited a higher frequency of anti-cardiolipin antibodies IgM (P < 0.001), whereas the medium-high titer group demonstrated a higher frequency of anti-β2-glycoprotein 1 antibodies IgG (P < 0.001) and IgM (P = 0.032). Moreover, the medium-high titer group displayed a significantly elevated erythrocyte sedimentation rate compared to the low-titer group (P < 0.05). In the low-titer group, 71 patients (77.2%) received appropriate treatment, resulting in 48 live births (67.6%) and 23 repeat abortions (32.4%). In the medium-high titer group, 29 patients (90.6%) received relevant treatment, leading to 23 live births (79.3%) and 6 repeat abortions (20.7%). No significant differences were observed in live births or maternal-fetal complications between the two groups (all P > 0.05).ConclusionNoteworthy distinctions in laboratory parameters were identified between the low-titer and medium-high titer groups. However, when appropriately treated, the fetal-maternal outcomes were comparable in both groups. Timely intervention by clinicians is imperative to enhance pregnancy outcomes in patients experiencing recurrent miscarriage with low levels of aPL.Key Points• This study challenges the conventional belief that only the higher antiphospholipid antibodies (aPL) titers directly correlated with worse pregnancy outcomes, which emphasized the importance of patients with low titer positive aPL-positive RM.• The results underscore the need for timely intervention in women with low titer aPL-positive RM, as it leads to favorable maternal–fetal outcomes.

Clinical profiles in pediatric systemic lupus erythematosus: a retrospective study

Aims: This study aimed to analyse clinical and laboratory findings, prognosis, and survival of systemic lupus erythematosus (SLE) patients, differentiating according to gender, pubertal status, and renal involvement. Methods: Ninety-six pediatric SLE patients, diagnosed using ACR criteria, were retrospectively analyzed. Inclusion criteria comprised age under 18, meeting at least four ACR criteria, and six months of monitoring. Data encompassed demographics, symptoms, diagnosis, organ involvement, autoantibodies, treatment, prognosis, and survival. Categorization was based on gender and pubertal status. Renal biopsies followed WHO-ISN classification, with asymptomatic findings termed “silent lupus nephritis.” Biopsied patients were divided into proliferative and non-proliferative lupus nephritis categories, excluding irreversible damage cases. Outcomes studied included remission, relapse, end-stage renal failure, and mortality. Results: Among 96 participants, females constituted 82.3%, males 17.7%, resulting in a female-to-male ratio of 4.6:1. Mean age at diagnosis was 11.9 years, with 37 prepubertal (38.5%) and 59 pubertal (61.5%) cases. Oral-nasal ulcers (p=0.01) were more prevalent in males related to system involvement. Nephrotic syndrome prevalence increased from 21.6% in prepubertal to 44.1% in pubertal cases (p=0.025). Positive Anticardiolipin IgM antibodies decreased from 56.2% in prepubertal to 25.9% in pubertal cases (p=0.047). Type IV lupus nephritis was predominant, followed by Type II, in prepubertal and pubertal groups and both genders. Proliferative lupus nephritis showed higher rates of renal involvement (95.7% vs. 65.6%), nephrotic syndrome (46.8% vs. 21.9%), proteinuria (89.4% vs. 62.5%), hematuria (57.4% vs. 28.1%), elevated creatinine (43.5% vs. 9.7%), and low albumin (67.4% vs. 23.3%). Cases with proliferative lupus nephritis had higher neuropsychiatric involvement (36.2% vs. 12.5%), seizures (25.5% vs. 3.1%, p=0.008), and increased hemolytic anemia rates (78.7% vs. 56.2%, p=0.033). Thirteen had silent lupus nephritis, revealing various types through biopsy. All reported deaths occurred within the first five years, resulting in stable 91% survival rates at 5, 10, and 15 years. Conclusion: This study provides insights into the clinical, prognostic, and survival characteristics of pediatric systemic lupus erythematosus (SLE), revealing notable patterns related to gender, pubertal development, and renal involvement. There is an association between proliferative lupus nephritis and renal involvement, nephrotic syndrome, and neuropsychiatric symptoms. Significantly, silent lupus nephritis highlights the complex renal implications, necessitating diligent surveillance for prompt intervention.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-β2-glycoprotein I(β2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and β2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Hematological Manifestations of Antiphospholipid Antibodies: A Case Series from South India

Introduction: Antiphospholipid syndrome (APS) is known for its association with unexplained vascular thrombosis and pregnancy-related complications. However, APS can also present with various hematological abnormalities, including thrombocytopenia, autoimmune hemolytic anemia, Evan's syndrome, and thrombotic microangiopathy. While APS is often considered in patients with these manifestations, its laboratory testing yield and patterns in hematology clinics remain underexplored. In this study, we aimed to investigate the prevalence of laboratory positivity for APS in patients attending hematology clinics, even in the absence of meeting the clinical criteria for APS. Methodology: This retrospective study was conducted at two tertiary care centers in southern India from January 2018 to June 2023. Patients who visited hematology clinics and underwent APS workup were included. The APS workup involved evaluating Anti Cardiolipin IGG and IGM, Anti Beta2 Glycoprotein IGG and IGM, Lupus Anticoagulant, and ANA. The laboratory criteria for APS were based on the ACR/EULAR APS Criteria. Patients with transiently positive results were excluded from the study. Chi Square test was used for statistical analysis. Results: Among the 624 patients who underwent APS workup, 100 patients (16.03%) tested positive for at least one of the laboratory criteria for APS. Remarkably, a significant proportion (56%)of these patients did not fulfill the clinical criteria for APS. The most common hematological manifestations prompting APS testing in these 100 patients were thrombocytopenia (38%) and unprovoked thrombosis (35%). Additional hematological abnormalities included autoimmune hemolytic anemia (13%), prolonged activated partial thromboplastin time (APTT) (5%), Evan's syndrome (4%), pancytopenia (4%), and thrombotic thrombocytopenic purpura (TTP) (1%). Baseline characterstics of our study subjects are shown in Table 1 Anti-beta2 glycoprotein IGG or IGM antibodies were detected in 74% of APS-positive patients, and Anti-cardiolipin IGG or IGM antibodies were found in 57%. Lupus Anticoagulant (LA) was present in 59%. Additionally, 28% of the patients showed positivity for all three antibodies, indicating a significant overlap in laboratory findings. No statistically significant difference in antibody positivity patterns was observed between patients satisfying the clinical criteria for APS and those without, as shown in Table 2 Conclusion: Our study sheds light on the hematological presentations of APS in patients attending hematology clinics in southern India. Importantly, a substantial number(56%)of patients with APS lab test positivity did not meet the clinical criteria for APS. These findings emphasize the importance of considering APS as a potential diagnosis in patients presenting with hematological manifestations, especially thrombocytopenia and autoimmune hemolytic anemia. Identifying APS in such cases can guide appropriate therapeutic interventions and may help prevent pregnancy-related complications in affected females. Raising awareness among healthcare professionals about the diverse hematological presentations of APS is vital for improving patient outcomes and ensuring timely and accurate diagnoses

Prevalence, clinical significance, and persistence of autoantibodies in COVID-19

BackgroundInterest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19.MethodsWe enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit.ResultsA total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes.ConclusionA significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

HELLP Syndrome Developing at 14 Weeks of Gestation: An Extremely Rare Case Report and a Literature Review

Introduction: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a disease of pregnancy that occurs very rarely before 20 weeks of gestation. We report a case of HELLP syndrome developing at 14 weeks and 2 days of gestation. Case Presentation: A 33-year-old Asian primipara at 14 weeks and 2 days of gestation visited the emergency room with a fever and headache. Initial blood pressure was 140/70 mm Hg, tempera.ture 38.5°C, heart rate 130 beats/min with tachycardia. Her prenatal examination has been unre.markable, and fetal ultrasonography was within normal range. The laboratory results showed low platelet count with elevated liver enzymes, D-dimer, and fibrinogen but no sign of jaundice. Her WBC differential suggested a bacterial infection. Thus, we diagnosed early HELLP syndrome and immediately started conservative treatments. One day after admission, symptoms and laboratory results showed aggravation of the disease. We performed termination, followed by dilation and curettage for retained placenta. Her general condition improved rapidly after the operation. Placen.tal biopsy showed both acute and chronic inflammation. She also had anticardiolipin antibody IgM, and after discharge, she was referred to a rheumatology specialist to address the antiphospho.lipid syndrome issue. Discussion: Although the triggers of HELLP syndrome are unclear, a recent inflammatory hypothesis suggests that placenta-derived inflammatory cytokines are involved. In our case, the anti-cardiolipin antibody may have triggered microangiopathy of the placenta. Our analysis of published HELLP cases revealed that, apart from the three diagnostic criteria, the most common abnormal laboratory finding was antiphospholipid antibodies. Therefore, despite its rarity, if a sign of inflammation is present in a patient, it is important to consider HELLP syndrome regardless of gestational age

FRI259 Antiphospholipid Syndrome And Adrenal Insufficiency: An Underrated Association

Abstract Disclosure: S. Khalid: None. M. Arumugam: None. P. Passarella: None. Introduction: Catastrophic Antiphospholipid Syndrome (CAPS) is a rare and life-threatening subtype of Antiphospholipid Syndrome (APS) that causes widespread vascular thrombi. Endocrine complications of APS are very rare, however the most common is Adrenal Insufficiency (AI). Overt AI is only found in 0.4% of patients with APS while only 0.5% of patients with AI are diagnosed with APS. Either thrombosis leading to infarction or hemorrhage can cause AI in patients with APS. Sometimes, adrenal insufficiency or crisis can be the primary presentation of APS. Here, we present a case of AI in the setting of CAPS. Case Presentation: A 17-year-old woman with past medical history of chronic immune thrombocytopenia was admitted to the intensive care unit due to cardiogenic and distributive shock. One week prior to her presentation she had developed a sore throat followed by progressive lethargy that eventually evolved into a state of unconsciousness and she was brought to the emergency department. Her presenting vital signs included temperature of 40.7 C and blood pressure of 89/36 mmHg. On physical exam, she appeared somnolent and pale, and had cool extremities. Labs on admission (11 pm) revealed cortisol level of 3.6 UG/DL (reference range 3.8-19.4 UG/DL), TSH 4.61 UIU/ml (reference range 0.45-4.5 UIU/ml), free T4 1.3 ng/dl (reference range 0.6-1.3 ng/dl), aldosterone 11.3 ng/dl (reference range supine &amp;lt; 3-39.2 ng/dl), sodium 135 MEQ/L (reference range 135-145 MEQ/L), and potassium 4.7 MEQ/L (reference range 3.5-5.2 MEQ/L). Echocardiogram was remarkable for new onset reduced ejection fraction of 25-30% and left ventricular thrombi. Additionally, brain MRI showed acute infarcts. Due to concern for an underlying rheumatological disease, extensive autoimmune work up was initiated, and she was started empirically on methylprednisolone 30 mg intravenous twice daily. To further evaluate thrombi, CT scan of the abdomen and pelvis was performed, revealing bilaterally enlarged and hypoenhancing adrenal glands likely related to ischemia or infarction along with left renal vein thrombosis. Laboratory work-up returned positive for anti-cardiolipin IgM and IgG antibodies. In the setting of multiple vascular thrombi and positive antibodies, she was diagnosed with CAPS. The diagnosis of AI was made due to a low cortisol level in a state of shock and was deemed secondary to CAPS. For the treatment of CAPS she was continued on methylprednisolone with a plan for a slow taper. To ensure mineralocorticoid replacement was adequate fludrocortisone was also added at a dose of 0.1 mg with close monitoring of electrolytes and vital signs. Conclusion: Our case illustrates a rare though potentially fatal endocrine complication of CAPS and highlights the importance of its awareness. Undiagnosed and untreated adrenal insufficiency can lead to extremely poor outcomes, including death. Presentation: Friday, June 16, 2023

A double-blind, randomized controlled trial of hydroxychloroquine for cognitive dysfunction and antibody biomarkers in systemic lupus erythematosus patients

Link of Video Abstract: https://youtu.be/51QxGpETzG0 Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to persistent inflammation, resulting in organ tissue damage. Cognitive dysfunction is one of the symptoms often found in NPSLE, and hydroxychloroquine is recommended for all levels of SLE from mild to severe. However, studies on the efficacy of hydroxychloroquine for cognitive dysfunction have not been studied. Therefore, this study aimed to evaluate the effect of hydroxychloroquine administration on antibody levels and cognitive function in lupus patients with cognitive dysfunction. Methods: A Randomized Controlled Trial (RCT) was conducted in patients with SLE who experienced cognitive dysfunction. The treatment group consisted of 20 subjects subjected to standard therapy along with a daily dosage of hydroxychloroquine (200 mg/day) for 8 weeks. Furthermore, the control group comprised 20 subjects who only received standard therapy. The primary outcome of this trial focused on the evaluation of MoCA-INA and sub-MoCA-INA scores, while the secondary outcome included the measurement of anti-NMDA, anti-β2-glycoprotein-1, anticardiolipin IgM and IgG antibodies, as well as lupus anticoagulant levels. Data analysis for unpaired variables used the independent t-test or the Mann-Whitney test. Results: There was a relationship between giving hydroxychloroquine administration to increasing the sub-MOCA-INA attention score (p&lt;0.05). However, there was no relationship between giving hydroxychloroquine to increasing MoCA-INA scores and decreasing biomarker levels of anti-NMDA, anti-β2-glycoprotein-1, IgM-IgG anticardiolipin, and lupus anticoagulant (p&gt;0.05) Conclusion: Administration of hydroxychloroquine only affected attentional MoCA-INA sub-scores but did not affect other MoCA-INA sub-scores, overall MoCA-INA scores, and antibody levels.

Bilateral retinal hemorrhages after sequential endovascular treatment of bilateral unruptured cerebral aneurysms.

To report a case of bilateral retinal hemorrhages in a patient undergoing two separate endovascular interventions for bilateral cerebral aneurysms. A comprehensive ophthalmic examination was performed after the patient underwent each of two separate endovascular interventions for bilateral cerebral aneurysms. Multimodal imaging including widefield pseudocolor fundus photography, optical coherence tomography, and widefield fluorescein angiography (FA) was obtained. A systemic workup including genetic testing and hypercoagulability studies was performed. Dilated fundus examination revealed new visually significant ipsilateral retinal hemorrhages after each endovascular procedure. FA showed evidence of a peripheral retinal microangiopathy present in both eyes before the patient underwent her second endovascular procedure. Systemic workup revealed persistently elevated serum anticardiolipin IgM antibody levels at >99th percentile. Retinal complications after endovascular intracranial interventions are uncommon. This patient who developed bilateral retinal complications was found to have persistently elevated anticardiolipin antibody levels, a risk factor for thrombosis. Patients who develop retinal complications after endovascular intracranial intervention may benefit from systemic workup for hypercoagulable conditions.

Antiphospholipid Antibodies Occurrence in Acute SARS-CoV-2 Infection without Overt Thrombosis.

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-β2 glycoprotein I antibodies (aβ2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aβ2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases (p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer (p = 0.016), aPTT (p = 0.001), ferritin (p = 0.012), C-reactive protein (CRP) (p = 0.027), lymphocyte (p = 0.040), and platelet (p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Abstract Number ‐ 225: COVID‐19 As A Potential Inducer Of Antiphospholipid Syndrome In A Patient With Acute Ischemic Stroke

Introduction COVID‐19 has been linked to hypercoagulability and acute ischemic stroke, though the precise mechanism is not well understood [1]. Various mechanisms have been suggested, including the potential release of autoantibodies‐ either via self‐production or exacerbation of the release of already produced autoantibodies [2‐3]. Antiphospholipid antibodies have been identified in severe disease [3‐4] and implicated in thrombosis [1‐2], though the significance is unclear. In this report, we describe a young woman with asymptomatic COVID‐19 presenting with acute ischemic stroke and postulate it was a manifestation of activated autoimmunity from COVID‐19. Methods Case Report Results A 22 year‐old previously healthy woman presented with acute onset dysarthria and right upper extremity weakness and numbness. On presentation, blood pressure was 158/101. NIHSS was 2 for right upper extremity drift and decreased sensation. Neurologic exam was otherwise unremarkable. Thrombolytic therapy was not administered given presentation outside the time window. CT head showed scattered left centrum semiovale hypodensities without hemorrhage. MRI brain demonstrated multifocal areas of diffusion restriction in the left centrum semiovale, anterior frontal lobe, and parietal lobe. CT angiogram demonstrated a possible thrombus at the left carotid bifurcation which was redemonstrated on MR angiography of the neck. No atherosclerotic plaque, hemodynamically significant stenosis, nor other vascular abnormality were appreciated. Heparin drip was started. Hemoglobin was 6.9 for which 1 unit of packed red blood cells was transfused. White blood cell count was 9.02. Platelet count was 761. PT/INR and PTT were 13.4/1.2 and 30.1. HIV was negative, RPR was positive at 1:128 titer, and COVID PCR was positive. She did not experience respiratory symptoms. Urine drug screen was positive for cannabinoids. LDL was 66. Transthoracic echo demonstrated minimal right to left shunting, suggesting patent foramen ovale. Ejection fraction was 60–65% and chamber sizes were normal. Bilateral lower extremity ultrasound was negative for deep vein thrombosis as a potential embolic source given cardiac shunt. Given history of miscarriage and extensive family history of sickle cell trait, possible lupus anticoagulant, and thrombosis at young ages, hypercoagulable workup was sent. Sickle cell preparation and ANA were negative. ESR was 12. High sensitivity CRP was 2.71. Anticardiolipin IgM antibody was elevated significantly at 125.9 MPL and IgG antibody was indeterminately elevated at 19.2 GPL. Beta‐2 glycoprotein IgM antibodies were also elevated at 42 SMUnits. Atypical neurosyphilis was considered given positive titer, middle cerebral artery distribution, and young age, but deemed unlikely given embolic rather than inflammatory stroke pattern [5]. Ultimately, with a possible diagnosis of antiphospholipid syndrome, anticoagulation was transitioned to warfarin via enoxaparin bridge with plan for repeat hypercoagulable workup as outpatient. Conclusions COVID‐19 has been observed in association with hypercoagulable states such as deep venous thrombosis and stroke. Here we present a case of COVID‐19 associated ischemic stroke with concomitant antiphospholipid antibodies. This case highlights the potential for even asymptomatic/mild COVID‐19 to induce autoimmunity through modulation of host antibody activity. This may be more profound in those with a predisposition to thrombosis. Autoimmunity should be considered in cases of concurrent COVID‐19 and acute ischemic stroke without clear etiology.

Decreased protein C activity, lower ADAMTS13 antigen and free protein S levels accompanied by unchanged thrombin generation potential in hospitalized COVID-19 patients

IntroductionCOVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown. Patients and methodsIn 118 adult Caucasian severe but non-critically ill COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram [CAT assay]) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications. ResultsCOVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE. ConclusionsIn COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

BackgroundImmune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19.MethodsStudy included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity.ResultsAntinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135).ConclusionIncreased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

POS0773 AUTOANTIBODIES IN A MULTI-INSTITUTIONAL INDIAN COHORT (INSPIRE) OF SLE PATIENTS: PREVALENCE, CLUSTER ANALYSIS AND PHENOTYPE ASSOCIATION

BackgroundSystemic Lupus Erythematosus (SLE) is characterized by an array of autoantibodies. Different autoantibodies have been associated with different clinical features like anti-dsDNA antibodies with nephritis and anti-phospholipid antibodies with pregnancy loss. However, the prevalence of autoantibodies has been variable across different ethnic groups. Data on the Indian population is limited.ObjectivesTo assess the prevalence of different autoantibodies in a multi-institutional cohort (INSPIRE) of Indian SLE patients and to test their association with various clinical features using cluster analysisMethodsThe patients (n=1053) enrolled in a multi-institutional cohort of Indian patients (Indian SLE inception cohort for Research [INSPIRE]) were included.1 Antibodies were assayed using Immunoline (Euroimmune, Germany) 17 antigen kit. Anti-phospholipid antibodies (IgG and IgM anti-cardiolipin antibodies (ACLs), IgG anti-Beta 2 GpI antibodies) were measured using ELISA (Euroimmune). Lupus anticoagulant was available in a subset of patients.The prevalence data for autoantibodies were analyzed using an intensity of only ++ and above on Immunoline assay as significant. Univariate analysis by Chi-square test was done to identify associations between individual autoantibodies and their clusters with clinical manifestations.ResultsThe clinical features were fever in 702, alopecia in 813, oral ulcers in 628, acute cutaneous lupus (ACLE) in 520, proteinuria in 400, pleural effusion in 181, thrombocytopenia in 250 and autoimmune hemolytic anemia in 137 patients.The prevalence of various autoantibodies by ELISA was anti-dsDNA antibodies in 70.2% (551/784), IgG Anti- beta-2 GpI in 4.47% (42/938), IgG ACL in 6.14% (61/992) and IgM ACL in 7.1% (54/760). Lupus anticoagulant was present in 13.9% (112/ 805). By Immunoline assay, the prevalence for anti-Ro 52, anti-Ro 60, anti-La and anti-Ribosomal P was 28.49%, 33.14%, 10.07% and 24.03% respectively (Table 1).Table 1.Prevalence of different autoantibodies in the INSPIRE lupus cohortS. No.AutoantibodyPrevalence (%) (n=1053)1.dsDNA28.112.Nucleosomes27.833.Histones24.884.Ro_52_SSA28.495.Ro_60_SSA33.146.SSB-La10.077.Ribosomal P24.038.nRNP36.759.Sm33.1410.Scl-703.2311.PM-Scl0.3812.Jo-10.0913.CENP-B0.3814.PCNA1.3315.AMA-M22.28Cluster analysis (Figure 1) revealed association (Odds ratio with 95% confidence interval) of Cluster 1 (antibodies against dsDNA, histones and nucleosomes) with arthritis (1.51 [1.18-1.94]), proliferative nephritis (3.05[2.08-4.48]) and pleural effusion (1.49[1.08-2.05]), cluster 2 (antibodies against Sm, nRNP, Ro52, Ro60 and Ribosomal P) with ACLE (1.3[1.02-1.65]) and non-proliferative nephritis (1.64[1.09-2.46]) and cluster 3 (antiphospholipid antibodies) with thrombocytopenia (3.34[1.57-7.11]).Figure 1.Cluster analysis of autoantibodies (Cluster 1: dsDNA, histone and nucleosome; cluster 2: Sm, nRNP, Ro52, Ro60 and Ribosomal P; cluster 3: cardiolipin, β2GP1 and La and lupus anticoagulant; cluster 4: Scl-70, Jo-1, PCNA, AMA-M2, PM-SCL and CENP-B)ConclusionThe prevalence of anti-Sm antibody and Anti-Ribosomal P antibody is higher whereas that of anti-La antibody is lesser in the Indian SLE patients as compared to other cohorts of SLE patients with different ethnicities.2 Cluster analysis reveals co-occurrence of different autoantibodies in our patients and their significant association with various clinical manifestations which suggests a possible pathogenic role of autoantibodies or a common genetic basis for it.

Aksiyel Spondiloartrit, Sistemik Lupus Eritematozus, Sjögren Sendromu ve Sekonder Antifosfolipid Sendromunun Birlikte Görüldüğü Olgu Sunumu

Hereby we report a 55-year-old female patient having the association of non-radiographic axial spondyloarthritis (nr-AxSpA), systemic lupus erythematosus (SLE), secondary antiphospholipid antibody syndrome (APS), and Sjögren's Syndrome (SjS). Diagnosis of nr-AxSpA was made based upon the presence inflammatory low-back pain, human leukocyte antigen B27 positivity, and presence of sacroiliitis only in magnetic resonance imaging (MRI). SLE was diagnosed with butterfly-shaped rash on her cheeks, inflammatory arthritis, photosensitivity, erythema involving dorsal inter-joint area of hand fingers, alopecia together with antinuclear antibody (ANA) and anti-dsDNA positivity, low serum complement levels, leucopenia and thrombocytopenia. Additional presence of sicca symptoms, low Schirmer I test, anti SSA/Ro and anti-SSB/La positivity, supported by positive labial salivary gland biopsy led to the diagnosis of SjS. Furthermore, this patient also had miscarriage at 16th week and cerebral vascular disease at 33 years. Besides, IgG and IgM anticardiolipin antibodies were found to be positive twice. Therefore, she was also diagnosed as secondary APS. She fulfilled the relevant classification criteria for AxSpA, SLE, SjS and APS. To our knowledge, this is the first case report showing the association of these four diseases, with different genetic, etiopathogenetic and clinical systemic inflammatory diseases.

Primary Antiphospholipid Syndrome with and Without Acute Myocardial Infarction/Angina: A Cross-Sectional Study.

IntroductionAcute myocardial infarct/angina (AMI-A) is a possible complication in primary antiphospholipid syndrome (pAPS) patients. This study compares data obtained from pAPS patients with and without AMI-A.MethodsThis cross-sectional study of 66 (85.2% female) pAPS patients (Sidney criteria). Demographics, clinical data, medication use, and antiphospholipid antibodies were evaluated. Patients were divided into two groups: pAPS with AMI-A and pAPS without AMI-A.ResultsSixty-six patients with primary APS (six with AMI-A and 60 without AMI-A) were selected. They were similar for demographics, disease duration, and anthropometrics (p > 0.05). Patients with AMI-A compared to those patients without AMI-A had more frequently dyslipidemia (66 vs. 28%, p = 0.05), systemic hypertension (83 vs. 37%, p = 0.02), and increased levels of lipoprotein (a) (116 ± 67 vs. 36 ± 35 mg/dl, p = 0.0002). Interesting, current physical activity (66.7 vs. 23%, p = 0.04) was more seen in the first group when compared to the second one. Patients with AMI-A used more statins (66 vs. 22%, p = 0.017) and acetylsalicylic (100 vs. 28%, p = 0.05). Higher median levels of IgM anticardiolipin antibodies [70 (0–120) vs. 9 (0–120), p = 0.03] were observed in the first group.ConclusionspAPS patients and AMI-A have distinct clinical and laboratory spectra from those without AMI-A. It is characterized by dyslipidemia and hypertension, hyper lipoprotein(a), and a lower IgM anticardiolipin frequency.

The Interaction of Sickle Cell Trait and Anticardiolipin Antibodies in Venousthromboembolism

IntroductionAmong the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population.MethodsA case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA.ResultsThe mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p<0.001). Sickle cell trait (Hb AS) occurred in the same number of patients and controls (eleven each). Higher levels of both IgG and IgM anticardiolipin antibodies were found among the VTE patients with sickle cell trait than controls. (Table 1) The mean levels of IgG antibody in Hb AS patients was 31.7 ± 12.8 GPL compared to 25 ± 13.8 GPL in the controls (p= 0.254) and mean IgM anticardiolipin antibodies in Hb AS patients was 18.7 ± 6.2 GPL while that of the controls was 16.8 ± 11.6 GPL (p= 0.633). The global mean levels of IgG and IgM anticardiolipin antibodies in the patients with VTE were 29.7 ± 9.1 GPL and 24.8 ±16.7 GPL respectively versus 28.5 ±13.7 GPL and 25.2 ±16.2 GPL in the controls. A multivariable logistic regression showed age, sedentary lifestyle and anemia as independent risk factors while a positive IgM anticardiolipin antibody appeared protective for VTE. (Table 2)ConclusionThe prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Laboratory Analysis of Antiphospholipid Antibodies with Clinical Correlation: A Hospital-Based 10 Year Study

Abstract Introduction/Objective Antiphospholipid syndrome (APS) is an autoimmune disorder and its diagnosis requires both laboratory evaluation of antiphospholipid antibodies (APAs) and clinical correlation. This study focused on the laboratory analysis of APS with clinical correlation in a hospital-based patient population. Methods/Case Report From 2010-2020, immunological studies for APAs were performed at Department of Pathology, William Beaumont Hospital – Troy, Michigan and patients with positive results were selected for further analysis. Four APAs were included: IgG and IgM beta-2 glycoprotein I antibodies (IgG B2GA and IgM B2GA), and IgG and IgM anticardiolipin antibodies (IgG ACA and IgM ACA). Clinical information was collected from hospital electronic medical chart with focus on thromboembolism and abortion history, autoimmune disorders, antithrombotic therapies and other studies. Results (if a Case Study enter NA) There were 167 patients, 136 females and 31 males (F/M=4.4). The median age for females was 50 and for males, 57. Overall, B2GA was present more than ACA (102/81) in females, and ACA was present slightly more than B2GA (20/17) in males. IgM APAs were much more common than IgG APAs; IgM B2GA/IgG B2GA: 87/32 (p&amp;lt;0.01) and IgM ACA/IgG ACA: 81/20 (p&amp;lt;0.01). Most APAs were at the low-intermediate titer range and increased APAs titer correlated with decreased positive rate: APAs titer at 20-40, 41-80 and &amp;gt;80 with positive results at 115, 61 and 44 respectively. In addition to documented autoimmune disorders, pregnancy miscarriage was a common clinical condition (24/66) in females at age &amp;lt;45. But for females at age &amp;gt;45, vascular thrombosis became more common (18/70). Vascular thrombosis was a common clinical disease in males (16/31) followed by autoimmune disorders (10/31). Most patients with vascular thrombosis received antithrombotic therapies. Conclusion Female patients positive for APAs was significantly more and younger than males in this study. IgM B2GA was the most common type of APAs followed by IgM ACA. IgG B2GA and IgG ACA were much less common. In younger female patients autoimmune disorders and abortion were the most common clinical conditions. In older female and male patients, autoimmune disorders and vascular thrombosis were the most common clinical conditions. The titer of APAs detected was at low-intermediate range in most patients. The relationship between the titer of APAs and clinical conditions needs further study.

P028 Aortic thrombosis with persistently positive antiphospholipid antibodies in a patient with COVID-19 pneumonitis

Background/Aims Arterial thrombosis and positive antiphospholipid antibodies have been reported following COVID-19 infection. We report a case of aortic thrombosis occurring after COVID-19 pneumonitis, with persistently positive anticardiolipin antibodies. Methods A 63-year-old lady presented with sudden onset of abdominal pain radiating to the back, associated with vomiting. She reported feeling slightly breathless, and ten days prior to admission a throat swab for SARS-CoV-2 tested positive. Oxygen saturation was 96% (94-100%) on room air. Respiratory examination revealed minimal basal crackles bilaterally. Her heart sounds were normal, and there was no carotid or subclavian bruit. Radial, ulnar, brachial, subclavian and temporal pulses were intact and symmetrical. The abdomen was soft, but tender over the right upper quadrant and epigastrium. Nailfolds were normal, and there was no livedo reticularis and no vasculitic rash. Initial investigations showed a CRP of 235 mg/L (<5), White blood cell count 15.2 x109/L (4.0-11.0), neutrophil count 12.6 x109/L (1.7-7.5). She was reviewed by the surgical team and CT Thorax, Abdomen and Pelvis requested due to the high CRP. Results CT showed a mild COVID pattern pneumonitis, inflammatory changes around the infrarenal aorta containing irregular circumferential clot, raising the suspicion of aortitis. An autoimmune screen was requested with following Results positive IgM Anti-Cardiolipin Antibodies (ACL) at 34.6 U/mL (0.0-20.0), IgG ACL 8.5 U/mL (0.0-20.0), Anti-B2-GP1 (B2GP1) Antibodies negative, Lupus anticoagulant (LAC) was not tested as patient was already on Low Molecular Weight Heparin (LMWH). ANA screen, Anti-ENA screen, ANCA screen, Crithidia Lucillae (dsDNA), RF, Anti-CCP Antibodies, Complement C3 and C4 were all negative. No steroid treatment was commenced. The patient then self-discharged against medical advice and was reviewed as an out-patient. CT scan was reviewed by a vascular radiologist who confirmed the suspicion of aortitis. Subsequently, a 5-Fluorodeoxyglucose-Positron Emission Tomography (FDG PET) CT scan showed no evidence of active, ongoing large vessel vasculitis. A short, linear focus of mild increased FDG uptake associated with some calcification within the left lateral abdominal aortic wall was more typical of atheromatous disease than vasculitis. LMWH was switched to long-term warfarin. She has now fully recovered from COVID and has remained well. Repeat Antiphospholipid screen taken more than 12 weeks later showed a positive IgM ACL (40.2 U/mL), and negative IgG ACL and B2GP1. Once again LAC was not tested as the patient has continued warfarin. IgM ACL positivity following COVID-19 infection has been reported by several other centres. Conclusion Our understanding of the significance of positive antiphospholipid antibodies and COVID-19 infection is evolving. Further research is needed to establish if there is a relationship between COVID-19 infection, thrombosis and positive ACL or if this is an epiphenomenon. Disclosure M. Curuvija: None. K. Hawkins: None. S. Al-Mudhaffer: None. E.P.M. Humphreys: Honoraria; E.H. has participated in advisory board meetings for Pfizer. Other; E.H. has received sponsorship to attend conferences from Abbvie, UCB and Celgene.

MiR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-β2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.