IgM Anticardiolipin Antibodies Research Articles

Visual and somatosensory evoked potentials abnormalities among Behçet’s disease patients and their relation to disease activity, severity and antiphospholipid antibodies: a cross-sectional study

BackgroundBehçet’s disease (BD) is a common disease with high morbidity and mortality. Ocular, neurological, and vascular affection in BD are a major cause of such morbidity and mortality. Evoked potential (EP) studies including visual evoked potentials (VEP) and somatosensory evoked potentials (SSEP) in addition to antiphospholipid antibodies (aPL) are valuable tools for detection of ocular, neurological and vascular affection and may be used for assessment of activity and severity in BD. We aimed to use EP studies and aPL as objective tools in BD assessment.ResultsAbnormal VEP was found in 76% of BD patients and has a significant association with ocular involvement (P = 0.003), Moreover, Abnormal VEP was significantly associated with ocular activity (P = 0.002). Abnormal SSEP in both median and tibial nerves was found in 62% of patients, prolonged central conduction time of median and tibial nerves was found in 46% and 22% of patients respectively and was significantly associated with neurological involvement in BD (P < 0.05). Abnormal VEP and SSEP studies were significantly associated with BD disease severity (P < 0.05) but not activity. Vascular involvement was significantly associated with elevated lupus anticoagulant and anti-cardiolipin IgM antibodies (P < 0.05), elevated lupus anticoagulant levels were associated with optic nerve involvement and abnormal VEP.ConclusionAbnormal VEP and SSEP studies can be considered as indicators for BD severity and hence poorer prognosis. VEP study is a valuable tool in BD and may indicate ocular involvement or ocular activity. Prolonged Central conduction time of upper limb and lower limb evaluated by N13- N20 IPL and N22-P39 IPL respectively may be used to detect nervous system involvement in BD patients. Optic nerve involvement may be suspected in BD patients with elevated lupus anticoagulant, elevated LA and aCL IgM can be used as indicators for vascular involvement in BD.

CAPILLAROSCOPIC FINDINGS IN ANTIPHOSPHOLIPID SYNDROME

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis and high levels of antiphospholipid antibodies (aPL). The disease mainly affects women over 30 years of age and can occur as a primary syndrome (PAPS) or in the context of another autoimmune disease (secondary APS). Antiphospholipid antibodies (aPL) can cause blood clots to form in the veins and arteries and lead to heart attack, stroke, pulmonary embolism, preeclampsia, miscarriage, slow growth or damage to the fetus, premature / stillbirth. Risk factors include arterial hypertension, obesity, hypercholesterolemia and hypertriglyceridemia, smoking, atherosclerosis, taking birth control pills or associated autoimmune diseases (such as systemic lupus, SLE). In patients with PAPS, capillary hemorrhages are associated with neurological manifestations and with comorbidity (most often with hypertension). In some people, the syndrome is asymptomatic, while in others the disease may present with deep vein thrombosis, bleeding from the nose and gums, unusually heavy menstruation, hematemesis, melena. Complications include pulmonary embolism, stroke, heart attack or transient ischemic attack in young people without risk factors for cardiovascular disease, kidney failure, miscarriages, etc. Treatment aims to reduce the risk of blood clots through anticoagulant therapy. Raynaud's phenomenon (RP) represents the most common clinical aspect of microvascular involvement and is a key feature of diseases such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM) and antiphospholipid syndrome (APS). Nail bed capillaroscopy (NVC) is an extremely useful, noninvasive, and reliable method for analyzing microvascular changes in Raynaud's phenomenon and systemic diseases, as well as for determining disease severity and prognosis. The presence of autoantibodies or capillaroscopic changes are essential for the early diagnosis of APS. It is not well established whether patients with primary antiphospholipid syndrome (PAPS) have specific capillaroscopic findings, but patients with positive IgG and IgM anticardiolipin antibodies have a higher incidence of capillaroscopic changes compared to healthy controls. Changes in capillary length and the presence of symmetrical microhemorrhages have been described, which are associated with thrombotic events, suggesting direct damage to the vascular endothelium caused by antiphospholipid antibodies. Other changes described include slight disorganization of capillary arrangement, change in capillary morphology (dilated, branched, kinked, bushy), change in capillary loop length and shape (apical coiling, single crossing between loops with moderate coiling and double crossing between loops ), avascular zones and neoangiogenesis. Many authors emphasize the presence of an "atypical normal" capillaroscopic pattern or "non-specific capillaroscopic changes". Other authors, however, did not reveal a similar capillaroscopic pattern in patients with anticardiolipin antibodies. Oral anticoagulants can be the cause of a high frequency of isolated microhemorrhages, which is why it is mandatory to pay special attention to patients treated with them, with a view to specifying the reasons for the finding. Nevertheless, capillaroscopy remains a valuable diagnostic tool in the differential diagnosis of many connective tissue diseases (occurring with or without Raynaud's phenomenon) as well as in aiding the diagnosis of antiphospholipid syndrome (APS), as cases of seronegative (regarding antiphospholipid antibodies) patients with clinical manifestations of APS.

Monoclonal Gammopathy in Patients with Neuropathy.

The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified. For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records. Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA). In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies.

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, temperature 38.5°C, heart rate 130 beats/min with tachycardia. Her prenatal examination has been unremarkable, 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. Placental 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 antiphospholipid 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

Comparison of Clinical and Laboratory Characteristics in Lupus Nephritis vs. Non-Lupus Nephritis Patients-A Comprehensive Retrospective Analysis Based on 921 Patients.

Background: Lupus nephritis (LN) is an inflammation of the kidneys that is related to systemic lupus erythematosus (SLE). This study aimed to evaluate the differences in clinical and laboratory characteristics between LN and non-LN SLE patients. Methods: We conducted a retrospective analysis of medical records collected from SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. All patients met the 2019 European League Against Rheumatism and the American College of Rheumatology (EULAR/ACR) criteria for SLE. Results: Among 921 SLE patients, LN was documented in 331 (35.94%). LN patients were younger at SLE diagnosis (29 vs. 37 years; p < 0.001) and had a male proportion that was 2.09 times higher than the non-LN group (16.62% vs. 7.97%; p < 0.001). They were more often diagnosed with serositis and hematological or neurological involvement (p < 0.001 for all). Hypertension and hypercholesterolemia occurred more frequently in these patients (p < 0.001 for both). LN patients exhibited a higher frequency of anti-dsDNA, anti-histone, and anti-nucleosome antibodies (p < 0.001 for all). Conversely, the non-LN group had a 1.24-fold (95% CI: 1.03-1.50; p = 0.021) increase in the odds ratio of having positive anti-cardiolipin IgM antibody results. LN patients were more frequently treated with immunosuppressants. The risk factors for experiencing at least three LN flares included female sex, younger age at the onset of LN or SLE, LN occurring later than SLE onset, the presence of anti-nucleosome or anti-dsDNA antibodies, and certain SLE manifestations such as myalgia, arthritis, proteinuria > 3.5 g/day, and pathological urinary casts in the urine sediment. Conclusions: LN patients differ from non-LN patients in the age of SLE diagnosis, treatment modalities, and autoantibody profile and have more frequent, severe manifestations of SLE. However, we still need more prospective studies to understand the diversity of LN and its progression in SLE patients.

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.

Prevalence of anticardiolipin antibody IgM and IgG in women with recurrent abortions in Kirkuk city

Abstract Toxoplasma gondii, a parasite that can produce a wide range of clinical symptoms in humans, is the source of the zoonotic infection known as Toxoplasmosis. The goal of this study was to measure the serum levels of anticardiolipin (ACL) antibodies (ACL-IgM and ACL-IgG) in 200 women with T.gondii and recurrent abortions. Two hundred (200) blood samples from aborted women were used in this study, which was carried out in Kirkuk between November 1, 2022, and March 21, 2023, at the Gynaecological &amp; Paediatric Hospital and Kirkuk General Hospital to determine the level of Anticardiolipin IgG and IgM serum. In this study of 200 aborted women, 28 (14%) had IgM positivity, 66 (33%) had IgG positivity, and 94 (47%) had Toxoplasmosis positivity overall. Of 200 aborted women, 39 (19.5%) had anticardiolipin IgM while 35 (17.5%) had Anticardiolipin IgG. The anticardiolipin IgM higher than anticardiolioin IgG in the Toxoplasmosis infected women.

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.

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.

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.

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.