Antiphospholipid Autoantibodies Research Articles

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age>18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p <0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Outcomes of IVF treatments in women with antiphospholipid antibodies or antiphospholipid syndrome

BackgroundOvulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear. Materials and methodsA retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared. Results121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive β-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle. ConclusionOvarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation.

Prevalence of antiphospholipid autoantibodies associated with biologics treatment for psoriasis

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.

Comparative assessment of the diagnostic performances of particle-based multianalyte technology and commercial ELISA for antiphospholipid autoantibody testing

Background: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-β2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. Methods: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT’s performance was evaluated against commercial ELISA in detecting aPL antibodies. Results: At the manufacturer’s suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88–90% specificity), IgA and IgM antibodies yielded 5.9–17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. Conclusions: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.

Criteria and non-criteria antiphospholipid autoantibodies screening in patients with late pregnancy morbidity: A cross-sectional study

IntroductionAntiphospholipid syndrome (APS) is a cause of pregnancy morbidity. We aim to determine the frequency of criteria and non-criteria anti-phospholipid (aPL) autoantibodies in patients admitted for unexplained fetal death (UFD), pre-eclampsia (PE) and/or fetal growth restriction (FGR). MethodsAll consecutive patients with UFD, PE and/or FGR followed in the department of Obstetrics, Bichat Hospital, University of Paris, Paris, between January 2019 and December 2021 were screened. Patients with available serum stored from the index pregnancy were included. Patients with previously known APS or twin pregnancy were excluded. Testing for aPL autoantibodies included anti-cardiolipin (aCL), anti-β2GPI (aβ2GPI), anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM and anti-annexin V IgG. When available, placenta specimens were analyzed by a pathologist blinded to the aPL status. All clinical characteristics, pregnancy features, and comorbidities were extracted from electronic medical records. ResultsOverall 167 (32 (28.8–35.7) years) patients with UFD (n = 28; 16.8 %), PE (n = 60; 35.9 %) and/or FGR (n = 105; 62.9 %) were screened for aPL autoantibodies. Moderate titers of aPL autoantibodies were detected in 33 (n = 33/167, 19.8 %) patients. aPL autoantibodies were non-criteria aPE IgG/IgM in most cases (n = 28/33, 84.8 %). aPS/PT IgG/IgM were found in 11 (n = 11/33, 33.3 %) cases and aCL or aβ2GP1 IgG/IgM in 4 (n = 4/33, 12.1 %). Multivariable logistic regression showed that aPL autoantibodies were mostly associated with UFD (OR 4.37 [1.72–11.20], p = 0.002), PE ≤ 34th week of gestation (3.22 [0.86–11.90], p = 0.070) and chronic deciduitis (8.03 [0.89–67.2], p = 0.060) DiscussionThe frequency of aPL autoantibodies, mostly aPE, is high in patients with late pregnancy morbidity and may qualify obstetrical APS.

Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation

Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4−CD8− double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.

P19 Our experience diagnosing and treating deficiency of adenine deaminase 2 (DADA2) vasculitis

Abstract Introduction Deficiency of adenine deaminase 2 (DADA2) is caused by biallelic pathogenic variants in the gene on chromosome 22q11. It is autosomal recessive with incomplete penetrance, and a variable presentation. It typically manifests as a systemic vasculopathy with early onset strokes, cutaneous manifestations, immunodeficiency and cytopenia. Traditional immunosuppressants have limited efficacy, but vasculitic manifestations have been reported to respond to biologic TNF-inhibitors. We report a patient with confirmed ADA2 deficiency whose cutaneous manifestations were previously classified as Sneddon syndrome. After a period of stability on adalimumab she developed marked cutaneous ulceration that healed following a therapy switch to intravenous infliximab. Case description We report a 39-year-old female with a long clinical history that started in childhood when she developed Diamond-Blackfan anaemia that went into remission following corticosteroid treatment and transfusions. In 2006, she suddenly had two thalamic infarcts and was thoroughly investigated but was found to have unremarkable vascular imaging, a negative antiphospholipid syndrome and autoantibody testing, a modestly elevated CRP (5-15 mg/L) and a notably persistent low serum IgM. She continued to experience frequent migraines associated with transient sensorimotor symptoms. Subsequently, she developed recurrent botchy, polymorphic macular eruptions on the lower limbs. A deep cutaneous biopsy demonstrated lymphocytic predominant perivascular inflammation of deep dermal vessels associated with thrombus formation and endothelial proliferation. A putative diagnosis of Sneddon’s syndrome was made. However, after the subsequent identification of ADA2-deficiency vasculitis, the patient underwent genetic screening which identified a compound heterozygosity for two novel ADA2 mutations (c6634_636, delTTC (p.Phe212del) and c.1225C&amp;gt;T (p.Pro409Ser)). Her mother was as a carrier. She was started on adalimumab injections to which she had a good clinical response with improved cutaneous disease and no further neurological symptoms. However, after two years of disease stability, she then developed a significant ‘punched out’ ulcer on the mid-calf which was painful and increasing in size to a maximum of 2 x 3 cm. Dermatology colleagues were reluctant to re-biopsy due to a high likelihood of non-specific appearances and increased risk of poor healing leading to worsening ulceration. Drawing on experience from rheumatoid arthritis that a switch in anti-TNF biological will often restore efficacy following secondary non-response to adalimumab; we empirically switched treatment to intravenous infliximab, with a reducing course of prednisolone (40mg per day tapering to 5mg after 12 weeks). This was associated with a notable improvement within one month and a complete healing of the ulcer within 4 months. Discussion DADA2 remains a rare condition with a carrier frequency estimated at 1 in 236 persons worldwide and a predicted disease prevalence of approximately 1 in 222,000 persons. Patients with DADA2 who have haematological manifestations tend to present during early infancy, whereas delayed presentation is common in patients with vasculitis and systemic inflammation. It should be suspected in patients with early onset strokes, livedo and other haematological and immunological features. Additionally, many previously diagnosed cases of Sneddon syndrome may in fact have DADA2, with a low IgM level favouring the later. Diagnosis can be confirmed by genetic studies or by a biochemical assay that demonstrates near-absent levels of ADA2 activity in the plasma or serum. Interestingly, on screening of adult patients with polyarteritis nodosa (PAN) 3.4% possessed biallelic pathogenic ADA2 variants and similarly, in genomic survey of patients with Diamond-Blackfan anaemia 2% possessed biallelic pathogenic ADA2 variants in the absence of the ribosomal protein gene mutations associated with it. Treatment is phenotype based with a preference for lifelong TNF inhibitor and biosimilar use in those with vasculitis and/or systemic inflammation, though not currently commissioned for this indication. Glucocorticoids, disease-modifying antirheumatic drugs, and other biologic agents may partially ameliorate systemic inflammation. Unfortunately, they are all ineffective for severe hematologic manifestations and hematopoietic cell transplantation (HCT) is currently the only treatment option. Treating asymptomatic patients and mildly symptomatic patients picked up on screening remains senior clinician led on a risk benefit basis. Disease activity is clinically monitored with an overall mortality rate estimated at 8%. Key learning points The main learning points for me included an increased awareness of this syndrome, its variable presentation, association with other autoimmune illnesses, diagnosis, and treatment initiation. In addition, I learnt about screening of family members, weighing the benefits versus risks when considering treating mildly symptomatic and asymptomatic patients, clinical monitoring for response, and when to switch to other anti-TNFs and biosimilars. From this conference, I would like to explore the experience of our rheumatology colleagues with similar cases.

MTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency

Transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). Transition from cirrhosis to hepatocarcinogenesis depends on mitochondrial oxidative stress, as controlled by cytosolic aldose metabolism through the pentose phosphate pathway (PPP). Progression to HCC is critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Although AR inactivation blocked susceptibility to hepatocarcinogenesis, it enhanced growth restriction, carbon trapping in the non-oxidative branch of the PPP and failed to reverse the depletion of glucose 6-phosphate (G6P) and liver cirrhosis. Here, we show that inactivation of the TAL-AR axis results in metabolic stress characterized by reduced mitophagy, enhanced overall autophagy, activation of the mechanistic target of rapamycin (mTOR), diminished glycosylation and secretion of paraoxonase 1 (PON1), production of antiphospholipid autoantibodies (aPL), loss of CD161+ NK cells, and expansion of CD38+ Ito cells, which are responsive to treatment with rapamycin in vivo. The present study thus identifies glycosylation and secretion of PON1 and aPL production as mTOR-dependent regulatory checkpoints of autoimmunity underlying liver cirrhosis in TAL deficiency.

Oxidative Stress as a Regulatory Checkpoint in the Production of Antiphospholipid Autoantibodies: The Protective Role of NRF2 Pathway.

Oxidative stress is a well-known hallmark of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. Oxidative stress may affect various signaling pathways and biological processes, promoting dysfunctional immune responses and inflammation, inducing apoptosis, deregulating autophagy and impairing mitochondrial function. The chronic oxidative stress and the dysregulation of the immune system leads to the loss of tolerance, which drives autoantibody production and inflammation with the development of endothelial dysfunction. In particular, anti-phospholipid antibodies (aPL), which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), play a functional role in the cell signal transduction pathway(s), thus contributing to oxidative stress and thrombotic events. An oxidation-antioxidant imbalance may be detected in the blood of patients with APS as a reflection of disease progression. This review focuses on functional evidence highlighting the role of oxidative stress in the initiation and progression of APS. The protective role of food supplements and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) activators in APS patients will be summarized to point out the potential of these therapeutic approaches to reduce APS-related clinical complications.

P09 A case of suspected COVID-19 vaccine-induced antiphospholipid syndrome

Abstract A 50-year-old man presented with an acute onset, painful leg ulcer affecting his right calf. This developed 2 weeks after his second COVID-19 vaccine. It started with a painful erythematous plaque, which evolved slowly into a deep-seated 5-cm ulcer over a 6-week period. A thorough review was unremarkable. He had no significant medical history and was a keen athlete and nonsmoker. His father had an unspecified stroke in his 80s. Examination revealed no signs of chronic venous insufficiency or discoloration to his foot, and his neurovascular examination was unremarkable. Investigations for antineutrophil cytoplasm antibodies, antinuclear antibody, complement, paraprotein, HIV and hepatitis were all unremarkable. Biopsy demonstrated nonspecific inflammatory changes, and wound swabs were unremarkable. Initial treatment with oral antibiotics, regular dressings, compression, topical emollients, Dermovate® and prednisolone (0.5 mg kg−1) was only partially effective. He subsequently developed additional painful superficial erosions and ulcers affecting the same limb involving the calf and shin, with a surrounding erythematous livedoid-like rash involving his shin. Rebiopsy demonstrated superficial and deep dermal and subcutaneous thrombosis without vasculitis. Direct immunofluorescence showed the presence of fibrinogen within dermal vessels. Further investigations demonstrated the presence of lupus anticoagulant. Factor V Leiden, protein C and S, anti-B2-GP1 and anticardiolipin antibodies, antithrombin III, homocysteine and coagulation profile were all unremarkable. Histological confirmation of thrombosis and the presence of serum lupus anticoagulant confirmed the diagnosis of antiphospholipid syndrome (APS). He was started on warfarin and the ulcers improved. APS is a rare autoimmune disorder characterized by recurrent miscarriage, thrombophilia and the presence of antiphospholipid autoantibodies (either serum lupus anticoagulant, anti-B2-GP1 or anticardiolipin autoantibodies). Positivity for APS antibodies can be found in up to 5% of the general population. An individual must have the clinical features and antibody positivity to be diagnosed with APS. The temporal relationship with his second COVID-19 vaccine raises the possibility of vaccine-induced APS. COVID-19 vaccine-induced APS is limited to just a few case reports (Moreno-Torres V, Gutiérrez A, Valdenbro M et al. Catastrophic antiphospholipid syndrome triggered by mRNA COVID-19 vaccine. Clin Exp Rheumatol 2022; 40:1054–5). It is postulated that mRNA vaccines may induce a rare complex immunogenic response characterized by a type 1 interferon reaction. This results in a prothrombotic cascade in individuals with pre-existing APS autoantibody positivity (Talotta R, Robertson E. Antiphospholipid antibodies and risk of post-COVID 19 vaccination thrombophilia: the straw that breaks the camel’s back? Cytokine Growth Factor Rev 2021; 60:52–60).

Antiphospholipid Autoantibodies and Brain Ischemic Lesions in Infective Endocarditis.

Stroke is a frequent and severe complication of infective endocarditis (IE).[1] [2] Although different factors associated with a high risk of embolic complications are known,[3] no biomarker has been identified yet. Various autoantibodies have been described in the course of IE, including antiphospholipid (aPL) autoantibodies.[4] [5] [6] Their detection at IE diagnosis may be of particular interest considering the risk of ischemic events. We aimed to determine the frequency of anticardiolipin (aCL), anti-β2GPI (aβ2GPI), antiphosphatidylethanolamine (aPE), and antiphosphatidyl/prothrombin (aPS/PT) autoantibodies in patients with IE and their association with brain ischemic events detected by systematic brain magnetic resonance imaging (MRI).

Predictors and clinical complications associated with antiphospholipid antibodies in sickle cell disease.

Although a higher prevalence of antiphospholipid autoantibodies (aPL) has been observed in some cohorts of sickle cell disease (SCD) patients, the clinical risk factors for the development of aPL and its associated complications remain unclear. In a retrospective study of 63 SCD patients, a lower hemoglobin concentration and higher white blood cell count were independently associated with an elevated aPL. SCD patients with elevated aPL had increased pregnancy complications (≥3 miscarriages, preterm delivery, pre-eclampsia) and venous thrombotic events. Our findings suggest that SCD may predispose to the generation of aPL and that aPL itself may contribute to the vasculopathy of SCD. Prospective testing for aPL is warranted in patients with SCD.

Antiphospholipid antibodies in pulmonary embolism treated with direct oral anticoagulants: Prevalence data from unselected consecutive patients

BackgroundDirect oral anticoagulants (DOACs) are the first-choice treatment option for the prevention of the recurrence of venous thrombosis in patients with pulmonary embolism (PE); however, their effect in patients with antiphospholipid syndrome (APS) is challenged. Therefore, the prevalence of antiphospholipid autoantibodies in patients with PE is noteworthy. ObjectivesTo determine the prevalence of unselected patients presenting with PE who meet the criteria for APS based on elevated levels of anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies. MethodsConsecutive patients with PE, in whom DOACs were primarily initiated, were tested for aCL and aβ2GPI. If the levels were elevated, the tests were repeated after 12 weeks for APS diagnosis. Laboratory results and patient characteristics were retrospectively collected from a laboratory information system and electronic patient journal entries over a 2-year period. ResultsThe prevalence of APS based on consistently elevated levels of aCL or aβ2GPI was 3.7% (10 of 267 patients). Three patients were double positive. In 11 out of 21 patients (52%) with initially elevated values, the levels of the antibodies normalized after 12 weeks. The patient characteristics were largely similar in those with APS and those without APS; however, patients with APS tended to be older and more likely to receive antithrombotic treatment at the time of PE. ConclusionWe found a relatively low prevalence of APS based on aCL or aβ2GPI. The high rate of normalized levels of the antibodies after 12 weeks reaffirms the need for repeated tests for APS diagnosis. Older patients more frequently met the criteria for APS. Determining the effectiveness of DOACs in non–triple-positive patients with APS following venous thromboembolism is important to further determine the feasibility of unselected tests in patients with PE.

Common Autoimmune Antibodies in Unexplained Infertile Female Patients in Saudi Arabia.

Unexplained female infertility is a devastating health problem that has become increasingly prevalent worldwide with no specific explanation despite comprehensive evaluations. Recent data suggestthat serum autoimmune antibodies are frequently found in patients with unexplained female infertility. This study aims to identify the prevalence of common autoantibody abnormalities in females with unexplained infertility in Saudi Arabia. A cross-sectional study was conducted on female patients with unexplained infertility sequentially referred to the allergy and immunology clinic at King Abdulaziz University Hospital (KAUH). Demographics, clinical characteristics, and 12 common autoantibody immunological tests were described as frequency and percentage. The chi-square test was applied to evaluate any associations. A total of 119 females with unexplained infertility were studied; of those, 97 (81.5%) had secondary infertility. Their average age was 33.9 ± 5.6 years ranging from 23 to 49 years. The overall prevalence of a high level of at least one autoantibody (above the normal range) was 84%. The predominant high autoantibodies were antithyroglobulin in 42 (35.3%), antithyroid microsomal in 41 (34.5%), beta 2 glycoprotein IgM in 40 (33.6%), antigliadin IgA in 32 (26.9%), antinuclear in 22 (18.5%), and anticardiolipin IgM in 18 (15.1%) of the participants. The following significant associations were found in our study: secondary infertility with beta 2 glycoprotein (p = 0.022), age with antithyroglobulin (p = 0.027), and the number of pregnancies with anti-tissue transglutaminase IgG and antigliadin IgA(p = 0.015 and p = 0.043, respectively). A high level of at least one autoantibody was detected in the majority of females with unexplained infertility. Antithyroid, antiphospholipid, antigliadin, and antinuclear autoantibodies were the most commonautoantibodies.These findings may encourage autoantibody screening in infertile females to discover any potential immunopathology in further clinical studies.

Predictors and Clinical Complications Associated with Antiphospholipid Antibodies in Sickle Cell Disease

Introduction. The antiphospholipid syndrome is characterized by the presence of anti-phospholipid autoantibodies (aPL) leading to a hypercoagulable state as well as an arterial, venous, and microcirculatory vasculopathy. Under several physiological and pathological situations, including the sickling of red blood cells (RBC), negatively charged phospholipids translocate from the inner to the outer surface of cell membranes leading to the potential generation of the antigenic target of aPL. We tested the following two-part hypothesis: 1) repeated exposure of the immune system of patients with sickle cell disease (SCD) to the antigenic target of aPL leads to an increased formation of aPL; and 2) the presence of aPL is associated with pregnancy and SCD-related complications. Methods. We conducted a cross-sectional study in 63 adults with SCD who had aPL testing performed during a hospital admission between August 1999 & June 2017. We compared individual aPL levels with categorical and linear variables using the Kruskal-Wallis test and linear regression analysis, respectively. The anticardiolipin (aCL) IgG and lupus anticoagulant (LA) levels were log-transformed for these analyses. An abnormal aPL was defined as any of the following: IgM or IgG anti-b2GPI >20 IU/mL, IgM or IgG aCL > 20 IU/mL, LA > 10 seconds. Clinical complications were compared by abnormal aPL status using the chi-square test. Results. The median age of the SCD cohort was 32 years (IQR, 21 - 39 years), 49 (78%) were female, 62 (98%) were African American, 5 (8%) had a diagnosis of systemic lupus erythematosus (SLE), 43 (68%) were Hgb SS genotype, 17 (27%) were on hydroxyurea, and 16 (25%) were on chronic anticoagulation therapy. SCD patients with SLE had higher median aCL IgM (6 vs. 1 IU/mL, respectively; P=0.02) and anti-b2GPI IgG (3.5 vs. 0 IU/mL, respectively; P=0.008) levels compared to those without SLE, while lower hemoglobin concentrations were associated with higher aCL IgG levels (β -0.12; P=0.07) and longer LA times (β -0.18; P=0.02). Fifteen of 63 (24%) patients with SCD had an abnormal aPL. Patients with an abnormal aPL had a lower hemoglobin concentration (Figure 1A), a higher white blood cell (WBC; 13.5 vs. 11.8 x109/L, respectively; P=0.06) count, and a lower platelet (268 vs. 340 x109/L, respectively; P=0.05) count at the time of hospitalization compared to those with a normal aPL. A lower hemoglobin concentration (odds ratio [OR], 1.9; P=0.008), a higher WBC count (OR 1.2; P=0.03), and a lower platelet count (10 platelets/µL increment: OR 1.05, P=0.06) were independently associated with the presence of an abnormal aPL by logistic regression analysis, adjusting for age, sex, and prior SLE diagnosis. Consistent with the second part of our hypothesis, several adverse outcomes trended higher in SCD patients with an abnormal aPL. An abnormal aPL was more prevalent among women with ≥ 3 miscarriages, preterm deliveries, or pre-eclampsia as well as during a hospitalization complicated by acute chest syndrome or multiorgan failure (Figure 1B). Conclusions. These data support the hypothesis that patients with SCD have a high predilection to form aPL, and that the presence of an abnormal aPL is associated with pregnancy complications and the severity of acute SCD-related complications during hospitalization. Our study is limited by its small number of patients. Further larger studies are needed to assess the mechanisms of aPL generation as well as to determine the prevalence and associated risk of abnormal aPL status in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

"True" Antiphospholipid Syndrome in COVID-19: Contribution of the Follow-up of Antiphospholipid Autoantibodies.

COVID-19 has led to more than 5 million deaths to date.[1] COVID-19 presentation can range from a simple asymptomatic viral infection to acute respiratory distress syndrome (ARDS)[2]; 15 to 20% of patients develop severe pneumonia and experience coagulopathy disorders. Severe COVID-19 occurs in the context of hyperinflammation that could potentially generate autoimmune disease.[3] We and others have shown the presence of antiphospholipid (aPL) autoantibodies in patients with COVID-19.[4] However, there remains contention if these aPLs represent transient antibodies associated with infection, or “true” aPL reflective of potential autoimmune-associated coagulopathy, namely, antiphospholipid syndrome (APS).[5] [6] Thus, only if they can be shown to persist for at least 12 weeks, can they be considered essential markers for the diagnosis of APS.[7] [8]

Effect of COVID-19 vaccination on the immune status and autoantibody profile in women of reproductive age

In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women’s reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the “Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age.The prospective study included 120 women who were vaccinated against COVID-19 with the “Gam-COVIDVac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies.The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response.Vaccination with “Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response.

Antiphospholipid and other autoantibodies in COVID-19 patients: A Singapore series

Dear Editor, Thrombosis is an unexpected complication of COVID-19 initially reported in 3 patients from China.1 These patients tested positive for immunoglobulin (Ig) A anticardiolipin (ACA), IgG anti-β2-glycoprotein I antibodies (aβ2GPI) and IgA aβ2GPI, though not for the lupus anticoagulant (LAC). In a Singapore study comprising 47,527 patients, 19 (0.04%) developed acute cerebral arterial and

Evaluation of personality disorders using the structured clinical interview for DSM-5 personality disorders, quality of life, and disease activity in patients with systemic lupus erythematosus.

This study aims to determine the frequency of personality disorders in patients with systemic lupus erythematosus (SLE) and healthy volunteers and to compare SLE patients with and without personality disorders in terms of quality of life (QoL) and other clinical and laboratory findings. Between January 2021 and March 2021, a total of 64 patients (17 males, 47 females; mean age: 42.9±10.8 years; range, 21 to 62 years) who were diagnosed with SLE and 68 age- and sex-matched healthy volunteers (20 males, 48 females; mean age: 40.9±10.6 years; range, 21 to 65 years) without any known disease were included. The Nottingham Health Profile (NHP) was filled in to evaluate the QoL for all participants. For the diagnosis of personality disorder, the Structured Clinical Interview For DSM-5 Personality Disorders (SCID-5PD) form was used. Clinical and laboratory findings of patients with SLE were noted and disease activity index (SLEDAI) was calculated. Clinical and laboratory variables that may affect personality disorder were evaluated. The prevalence of personality disorder in SLE patients was significantly higher than the control group (39.1% vs. 11.8%, respectively; p<0.001). In terms of the subgroups of personality disorders detected in SLE, only the prevalence of obsessive-compulsive personality disorder was significantly higher than the control group (26.6% vs. 10.3%, respectively; p=0.015). The frequency of personality disorder increased, as the education level decreased, the duration of SLE disease increased, and with antiphospholipid autoantibodies positivity in patients with SLE (p<0.05). The mean NHP total score was 126.1±55.1 in SLE patients with personality disorder and 62.9±43.8 in patients without personality disorder, indicating that the QoL of SLE patients with personality disorder was worse than those without personality disorder (p<0.001). The frequency of personality disorder in SLE seems to be higher than in the control group. Quality of life is adversely affected in SLE patients with personality disorders. Therefore, clinicians should be alert for personality disorders that may accompany SLE and fight with personality disorder with early diagnosis and optimal treatment.

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49). A total of 157 sera of patients infected by SARS-CoV-2 were collected. A large aPL panel including lupus anticoagulant, anti-cardiolipin and anti-beta-2 glycoprotein I (IgG, IgM and IgA), anti-phosphatidylethanolamine IgA, anti-prothrombin (IgG and IgM) was retrospectively analyzed according to the disease severity. We found a total aPL prevalence of 54.8% with almost half of the cases having aCL IgG. Within an extended panel of aPL, only aCL IgG were associated with COVID-19 severity. Additionally, severe patients displayed higher CitH3 levels than mild patients. Interestingly, we highlighted a significant association between the levels of aCL IgG and exDNA only in aCL positive patients with severe disease. In conclusion, we showed a significant link between aPL, namely aCL IgG, and circulating exDNA in patients with severe form of COVID-19, that could exacerbate the thrombo-inflammatory state related to disease severity.