IgG Anticardiolipin Antibodies Research Articles

P030 Multiple autoantibody formation post COVID-19 infection

Abstract Background/Aims COVID-19 has been linked to the formation of a number of autoantibodies. This case is an important reminder to clinicians interpreting autoantibody results in conjunction with clinical manifestations. A previously fit 51 year old gentleman, with no prior history of autoimmune disease required admission with respiratory symptoms in April 2020 consistent with COVID-19 infection. His acute respiratory illness was complicated by empyema and left-sided pneumothorax requiring left pleural decortication and adhesiolysis under (VATS). Persistent respiratory symptoms and fatigue lead to investigations for long COVID. Positive antibodies detected were dsDNA 166IU/ml, Proteinase 3 antibodies 20IU/ml, Myeloperoxidase antibodies 32IU/ml, IgG anticardiolipin antibodies 90IU/ml and Glomerular basement membrane antibodies 351 IU/ml. Negative autoantibodies included ANA, RF, aCCP, b2GPI, smooth muscle, AMA and myositis related antibodies. Methods There were no clinical signs or symptoms of inflammatory arthropathy, vasculitis, thrombosis or connective tissue disease. Other investigations included a CT thorax showing no new lung lesions, unremarkable urine dipstick, normal urine ACR, normal US abdomen, CT sinuses and MRI brain. Results Trial course of prednisolone was given therapeutically due to long COVID symptoms. There was no significant impact on symptoms/ autoantibody titres thus steroids were discontinued. The patient was followed closely by the rheumatology team for two years. During that time, the autoantibody levels gradually decreased, and he did not develop clinical signs of autoimmune disease. His long COVID symptoms persisted, and he remains under the long COVID clinical team. Conclusion COVID-19 infection is known to cause an immune response. There have been published cases of positive ANA, U1-snRNP anti-SS-B/La, ANCA, anti-phospholipid and anti-SRP antibody formation following COVID-19 infection. The link between the pathophysiology of COVID-19, autoantibody formation and the role of autoimmunity is still unclear. This man's case was unusual in the number and variety of autoantibodies formed post COVID, this has not been reported in the literature to date. Some of the autoantibodies detected are highly specific for certain conditions, for example anti-GBM antibodies have a high specificity for Goodpasture’s syndrome, thus this case also illustrates the need to interpret positive autoantibodies in the context of clinical findings and history. Disclosure S. Islam: None. N. Erb: None.

E031 Retinal vasculitis with Libman-Sacks endocarditis as presenting features of a systemic lupus erythematosus with antiphospholipid antibody syndrome patient

Abstract Background/Aims Ocular manifestations of systemic lupus erythematosus (SLE) are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with the active generalised disease. We report a case of a 22-year-old lady who was diagnosed with SLE with antiphospholipid antibody syndrome (APS) as the initial presentation of retinal vasculitis and Libman-Sacs endocarditis. Methods A 22-year-old lady with a background history of benign hypermobility spectrum disorder, presented to the eye casualty with a 4-week history of right-sided visual disturbances and was diagnosed with retinal vasculitis associated with uveitis, central retinal vein occlusion with multiple emboli in the retinal artery of the right eye and a single embolus in the left eye. In terms of family history, both father and brother were diagnosed with spondyloarthropathy, and the maternal uncle had Sjogren’s syndrome. She was then referred to the medical team for proper evaluation. On query, she mentioned photosensitive rash on her face getting worse in sunlight, a history of Raynaud’s phenomenon, significant hair loss, and one miscarriage before the 10 weeks of gestation. On examination, mild alopecia and a faint butterfly rash on the face were noted. Cardiac auscultation revealed pansystolic murmur. The rest of the systemic examinations were unremarkable. Results The blood test showed thrombocytopenia (130 u/L), positive antinuclear antibody (1:80, speckled pattern) with anti-double stranded DNA (26 IU/L), low complement (C3-0.74, C4- 0.12), markedly raised anticardiolipin antibody IgG (2016 u/ml), anti beta 2 glycoprotein 1 IgG ( >6100 u/ml) including presence of lupus anticoagulant. Her urinary protein creatinine ratio was 66mg/mmol. 3 sets of blood cultures came back negative. Transthoracic echo showed vegetation on the posterior mitral valve leaflet (0.95x 1.2cm) with moderate mitral regurgitation while transesophageal echo additionally found the possibility of perforation at the junction of leaflets of the mitral valve which was later confirmed by cardiac magnetic resonance imaging (MRI). The head MRI scan did not show any central nervous system abnormality. She was initially treated with 500mg intravenous methylprednisolone for 3 days followed by 20mg oral prednisolone daily with gradual tapering. Hydroxychloroquine and mycophenolate mofetil were added. Her case was discussed in the cardiology multidisciplinary team meeting and an opinion from the cardiothoracic surgery was taken to consider valve replacement in the future. Due to aspirin allergy, only warfarin was considered for APS. She had 2 sessions of pan-retinal photocoagulation as well. In subsequent follow-up, it was noted significant improvements in terms of her symptoms. Conclusion Vaso-occlusive retinopathy is a rare, potentially vision-threatening initial manifestation of SLE, which can be an indicator of active disease. Early identification of patients is necessary for timely intervention and multidisciplinary team involvement is required for comprehensive treatment plans. Disclosure M. Islam: None. S. Quddus: None. M. Hughes: None. R. Kumar: None.

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

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 < 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

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.

ANAESTHETIC CONSIDERATIONS OF ANTI-PHOSPHOLIPID ANTIBODY SYNDROME IN PREGNANCY

Anti-phospholipid syndrome (APS) is a systemic autoimmune acquired disease characterised by vascular thrombosis or pregnancy complications with the presence of antiphospholipid antibodies. It is a rare disease affecting 40-50/100,000 population and 10%-15% of recurrent abortions. Perioperative management in obstetric APS undergoing caesarean section stresses on the management of anticoagulation and prior choice of anaesthetic technique. We report the case of 26 year old multigravida ,37 weeks of gestation diagnosed with APS since 8 weeks of gestation. She had previous three miscarriages with lupus anticoagulant(LAC) value of 45.6 (normal – 36.8), IgM and IgG anticardiolipin antibody values were 8.5µ/ml and 3.8µ/ml, respectively. She was prophylactically put on Aspirin 75mg orally and Enoxaparin 0.4IU subcutaneously every 24 hours. She presented to the obstetric department and was planned for emergency caesarean section . She received her usual dose of enoxaparin on the day of surgery but aspirin was omitted. Surgery was conducted under subarachnoid blockade. Anticoagulation resumed 12 hours after surgery .No maternal and fetal complications were noted

Lupus Anticoagulant and Anticardiolipin Antibody IgG are Associated with Increased Atherosclerosis at the Suprainguinal Elastic and Infrainguinal Muscular Arteries in the Abdomen and Lower Extremities

PurposeWhether antiphospholipid antibodies (aPLs) cause atherosclerosis in certain arteries with specific compositions and locations remains unknown. We investigated the relationship between aPLs and their association with locations of atherosclerosis in the arteries of the abdomen and lower extremities.MethodsOf 2273 patients, 697 who underwent computed tomography angiography of the abdomen and lower extremities and aPL evaluation were included. Atherosclerosis distribution score (ADS) was employed to quantify atherosclerosis severity. Multiple linear regression analysis was performed using the ADS of the suprainguinal elastic and infrainguinal muscular arteries as dependent variables and all aPLs, conventional risk factors of atherosclerosis, and coagulation-related factors as independent variables.ResultsIn the suprainguinal elastic and infrainguinal muscular arteries, common risk factors for higher ADS were age, smoking, hypertension, higher glycated hemoglobin, male sex, decreased protein S, and increased homocysteine. Lupus anticoagulant (LA) and increased triglyceride level in the suprainguinal elastic arteries and anticardiolipin antibody (aCL) immunoglobulin (Ig)G, longer alcohol consumption duration, and increased fibrinogen level in the infrainguinal muscular arteries were also risk factors for higher ADS.ConclusionLA and aCL IgG were associated with atherosclerosis in the suprainguinal elastic and infrainguinal muscular arteries, respectively. aPLs could predict the location of atherosclerosis.

SUBCLINICAL PREDICTORS OF HEART FAILURE IN UNTREATED SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITHOUT KNOWN HEART DISEASE

SUBCLINICAL PREDICTORS OF HEART FAILURE IN UNTREATED SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITHOUT KNOWN HEART DISEASE

Antinuclear antibody-negative systemic lupus erythematosus: How many patients and how to identify?

This study aims to the prevalence of antinuclear antibody (ANA)-negative systemic lupus erythematosus (SLE) and their clinical characteristics in a large single-center SLE inception cohort to provide guidance for early diagnosis. Between December 2012 and March 2021, the medical records of a total of 617 firstly diagnosed SLE patients (83 males, 534 females; median age [IQR]: 33+22.46 years) who fulfilled the selection criteria were retrospectively analyzed. The patients were divided into groups with ANA-negative SLE and ANA-positive SLE, or with prolonged use of glucocorticoids or immunosuppressants (SLE-1) and without (SLE-0). Demographic, clinical characteristics, and laboratory features were collected. The total prevalence of ANA-negative SLE patients was 2.11% (13/617). The prevalence of ANA-negative SLE in SLE-1 (7.46%) was significantly higher than that in SLE-0 (1.48%) (p<0.01). The ANA-negative SLE patients had a higher prevalence of thrombocytopenia (84.62%) than ANA-positive SLE patients (34.27%). As with ANA-positive SLE, ANA-negative SLE also had a high prevalence of low complement (92.31%) and anti-double-stranded deoxyribonucleic acid (anti-dsDNA) positivity (69.23%). The prevalence of medium-high titer anti-cardiolipin antibody (aCL) IgG (50.00%) and anti-ß2 glycoprotein I (anti-ß2GPI) (50.00%) of ANA-negative SLE was significantly higher than that of ANA-positive SLE (11.22% and 14.93%, respectively). The prevalence of ANA-negative SLE is very low, but it exists, particularly under the influence of prolonged use of glucocorticoids or immunosuppressants. Thrombocytopenia, low complement, positive anti-dsDNA, and medium-high titer antiphospholipid antibody (aPL) are the main manifestations of ANA-negative SLE. It is necessary to identify complement, anti-dsDNA, and aPL in ANA-negative patients with rheumatic symptoms, particularly thrombocytopenia.

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.

Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms.

BackgroundProliferative vasculopathy (PV) associated antiphospholipid syndrome (APS) in the central nervous system is a rare un(der)recognized form of extra-criteria manifestations of APS. This study investigated the angiographic characteristics of cerebral and cervical arteries in patients with PV associated with antiphospholipid antibodies (aPLs).MethodsPatients with aPLs, neurologic symptoms and diffuse luminal narrowing on brain or neck magnetic resonance angiography were selected from electronic medical records. Vascular wall and intraluminal pathology were examined by high-resolution vessel wall MR imaging (VW-MRI).ResultsA total of 11 patients (six men and five women) with PV-aPL, of median (interquartile range) age 42 (34–61) years, were included. Median anticardiolipin antibodies IgG titer was 78.9 (28.2–134.0) units and anti-beta 2 glycoprotein I antibodies (aB2GPIs) IgG titer was 227.2 (0.0–1012.1) units. All patients had diffuse luminal narrowing in the carotid basilar and/or cerebral arteries, five in the internal carotid artery (ICA); two each in the middle cerebral artery (MCA) and vertebral artery; and one each in the basilar artery (BA) and posterior cerebral artery. On VW-MRI, four patients showed concentric thickening of the vascular walls of the ICA and/or MCA and two showed mild eccentric wall thickening of the ICA or BA. All patients received antithrombotic treatment. In two patients with extremely high aB2GPIs titer, diffuse narrowing progressed despite treatment with antithrombotic agents on follow-up imaging.ConclusionsThis study suggests that PV-aPL might be a distinct extra-criteria manifestation of APS that can manifest as long-segmental diffuse stenosis of cerebral and cervical arteries. It should be considered in relatively young patients with neurologic symptoms and aPLs.

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.

Retiform Purpura of the Lower Limbs Associated with Levamisole-Adulterated Cocaine.

A young man was treated in hospital for sepsis, disseminated intravascular coagulation and multi-organ failure. He was a regular intranasal cocaine user up to 1 day prior to symptom onset. Clinical examination revealed extensive retiform purpura affecting both his lower limbs. Skin biopsy revealed widespread thrombosis in the small- and medium-sized vessels of the mid dermis and the subcutaneous fat with surrounding leucocytoclasis. There was also extensive ischaemic necrosis of the upper reticular and papillary dermis and focal ischaemic necrosis of the epidermis. These findings were in keeping with a thrombotic vasculopathy with associated cutaneous ischaemic necrosis, likely associated with levamisole-adulterated cocaine (LAC). An autoimmune screen showed extremely raised levels of anti-B2-glycoprotein IgM, IgG and anti-cardiolipin IgG antibodies, usually seen in antiphospholipid syndrome (APS). The literature describes how APS could be secondary to various underlying conditions, including LAC, and that levamisole toxicity may mimic APS and hence be missed.LEARNING POINTSLevamisole is a common adulterant found in cocaine; the resultant toxicity can present with cutaneous manifestations, namely retiform purpura and skin necrosis, similar to antiphospholipid syndrome.Patients presenting with such features should be asked about illicit drug use, specifically cocaine, and investigated by screening urine for drugs of abuse and serum antihuman elastase antibody when possible.

Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters.

BackgroundAntinuclear antibodies (ANA) are major immunodiagnostic tools in systemic lupus erythematosus (SLE); however, their clinical and pathogenic roles are not yet elucidated and are a subject of controversy.ObjectivesThe aim of the study is to explore the pathogenic significance of ANA patterns among SLE patients, by analyzing their association with ANA titers, complement levels and other pathogenic immune markers, namely, anti-double-stranded DNA (anti-dsDNA), complements C3 and C4, rheumatoid factor (RF), anticardiolipin antibodies IgG (ACL IgG) and IgM (ACL IgM), Beta-2 Glycoprotein 1 Antibodies (β2-GP) IgG (β2-IgM) and IgM (β2-IgM), and lupus anticoagulant (LA).MethodA comparative cross-sectional study was conducted among 495 SLE patients, who were diagnosed and classified by consultant rheumatologists according to the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 criteria. SLE immunodiagnostic profiles were analyzed including the following parameters: ANA antibody titers and staining patterns, anti-dsDNA, C3 and C4 levels, aCL, and anti-β2-GP and LA.ResultThe most frequently observed ANA patterns were the speckled (52.1%) and homogeneous (35.2%) patterns, while other patterns were rare representing less than 7% of the patients each. ANA titers were highest in patients with mixed pattern followed by the speckled pattern. Of all the investigated patterns, the peripheral pattern showed the most pathogenic immune profile, namely, highest levels of anti-dsDNA, lowest levels of C4, and highest levels of aCL and β2-GP IgG and IgM.ConclusionThis retrospective study showed that speckled followed by homogeneous ANA patterns were predominant accounting for 52.1 and 35.2% of the patients. The ANA pattern showed several associations with other immune markers that are documented to have significant clinical implications in SLE. Peripheral, mixed, and speckled patterns were associated with higher profiles of immune markers indicative of a potential prognostic value of these patterns in SLE.

Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5-1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39. Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI -12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure. Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Dutch Organization for Health Research and Development, Fonds NutsOhra, Dutch Patient Organization of Thyroid Disorders, the Jan Dekkerstichting and Dr Ludgardine Bouwmanstichting, and a personal donation through the Dutch Patient Organization of Thyroid Disorders.

Context-dependent induction of autoimmunity by TNF signaling deficiency.

TNF inhibitors are widely used to treat inflammatory diseases; however, 30%–50% of treated patients develop new autoantibodies, and 0.5%–1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high-affinity autoantibodies are often made. We found that TNF deficiency in Sle1 mice induced TH17 T cells and enhanced the production of germline encoded, T-dependent IgG anti-cardiolipin antibodies but did not induce GC formation or precipitate clinical disease. We then asked whether a second hit could restore GC formation or induce pathogenic autoimmunity in TNF-deficient mice. By using a range of immune stimuli, we found that somatically mutated autoantibodies and clinical disease can arise in the setting of TNF deficiency via extrafollicular pathways or via atypical GC-like pathways. This breach of tolerance may be due to defects in regulatory signals that modulate the negative selection of pathogenic autoreactive B cells.

Levels and avidities of antiphosphatidylethanolamine antibodies in patients with thrombotic events and immunologically-mediated diseases.

Antiphosphatidylethanolamine antibodies (aPE) represent one type of antiphospholipid antibody (aPL) directed against the neutral phospholipids - phosphatidylethanolamines. The aim of this study was to evaluate levels and avidities of aPE in several groups of patients and compare them with conventional aPLs. aPE were analysed in a cohort consisting of 68 hospitalized patients. The other cohort comprised 22 patients with immunologically-mediated diseases. The control group consisted of 20 healthy persons. ELISA methods were used for determination of aPL. Avidities of aPE were tested by modified ELISA with urea as a chaotropic agent. aPE IgG/IgM were significantly higher in the group of patients with venous thromboembolism than those with non-thrombotic internal disorders (P=0.02 for both Ig classes). aPE IgG/IgM elevated above cut-off values were found in 10.8% of patients with venous thromboembolism and as a single aPL in 6.5%. Levels of aPE IgG higher than our limit (>6 U/mL) were detected in 29% of patients with immunologically-mediated diseases with other positive aPL. Low-, intermediate- and high-avidity aPE IgG were found in patients of both cohorts. The avidities of aPE IgG differed from those of anticardiolipin antibodies IgG. Neither aPE IgG levels nor avidity dynamics significantly changed during follow-up. aPE may be related to venous thromboembolism and may be part of the repertoire of aPL in immunologically-mediated diseases. There are patients with thrombosis negative for conventional aPL but positive for aPE. aPE IgG may have different avidities.

Thrombophilic risk factors and ABO blood group profile for arteriovenous access failure in end stage kidney disease patients: a single-center experience

Introduction Thrombosis of fistula occurs most frequently in end-stage kidney disease (ESKD) patients receiving hemodialysis. However, the role of thrombophilia in arteriovenous fistula (AVF) failure has not been well established. Hence, this study was aimed at assessing the roles of hereditary and acquired thrombophilic factors in association with AVF failure among patients with ESKD undergoing hemodialysis. Methods A cross-sectional study was conducted on 100 ESKD patients, of whom 50 patients with well-functioning AVFs with no fistula failures earlier were enrolled as Group 1, and 50 patients who have had AVF failure were enrolled as Group 2. The hereditary factors as factor V Leiden, factor XIII, prothrombin, and methylene tetrahydrofolate reductase and the acquired factors as lipoprotein (a), fibrinogen, homocysteine, and anticardiolipin antibodies IgG and IgM were studied. Results Among the hereditary factors, no statistically significant difference was observed in relation to factor V Leiden and Prothrombin (p > 0.05). However, for factor XIII and methylene tetrahydrofolate reductase, a statistically significant difference was observed between patients with well-functioning AVFs and patients who have had AVF failure (p < 0.05). We found a statistically significant increase in all the acquired factors in patients who have had AVF failure in comparison with patients with well-functioning AVFs (p < 0.001). Association between ABO blood groups and thrombophilic factors showed significant association between factor V Leiden, anticardiolipin antibody IgG and IgM and ABO blood groups (p < 0.05), whereas none of the other thrombophilic factors showed significant association (p > 0.05). Conclusion Thus, our study suggests significant role of acquired factors in causing AVF failure.

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.