Anticardiolipin Research Articles

IL-4 role in the development of the lupus mouse model induced by non-bilayer phospholipids arrangements

Abstract Non-bilayer phospholipids arrangements (NPAs) are lipid molecular associations that are different from the bilayer and are transient. However, if they become stable, they can trigger a disease in mice that is similar to human systemic lupus erythematosus. NPAs can be stabilized in liposomes formed by cylindrical and conical lipids or in cell membranes by drugs such as procainamide or chlorpromazine. In wild-type BALB/c mice, this lupus model has been developed by administering liposomes with NPAs induced and stabilized with procainamide or chlorpromazine, by administering the drugs alone or by administering the monoclonal antibody H308; these last two procedures stabilize the NPAs in the membranes of mouse cells. Anti-NPAs, anti-cardiolipin, anti-histones and anti-coagulants auto-antibodies have been detected in the serum of these mice; in addition, the mice present facial lesions and alterations in the skin and kidney. In this work, we evaluated the participation of the T H2 response, through IL-4, which is its most characteristic cytokine, in the development of the NPAs-induced lupus model in mice. Wild type or IL-4 knockout BALB/c mice were administered with liposomes bearing drug-induced NPAs, the drugs alone, or anti-NPA H308 antibody to induce the lupus-like disease. IL-4 KO mice showed minor disease manifestations, compared to wild-type mice, with decreased production of anti-NPA IgG antibodies, no anti-cardiolipin, anti-histones and anticoagulant antibodies, and no kidney or skin lesions. In these mice, H308 was the only inducer of anti-NPA IgG antibodies. These findings suggest that IL-4 has a key role in the development of the murine lupus-like disease induced by NPA stabilization. This study was supported by grants from IPN (SIP20232128, SIP20232132 and SIP20232135).

Role of Astrocytes in Epilepsy and Schizophrenia

The dangers of epilepsy and schizophrenia are increasingly being noticed. Its economic burden, social harm and harm to patients cannot be ignored. However, little is known about the pathogenesis of psychiatric disorders. Relevant treatment is limited to symptomatic treatment. Research suggests astrocytes play a role in seizures and schizophrenia. In the occurrence and development of mental diseases such as epilepsy and schizophrenia, astrocytes cannot be ignored. The article introduces the current findings and theories on role and function of astrocytes, and their connection with epilepsy and schizophrenia. It describes the positive effects and negative effects of astrocytes and their basic mechanisms that are now believed. And those mechanisms include glutamate-glutamine cycle which is related to the synthesizing of gama-aminobutyric acid (GABA), blood brain barrier which is controlling the matter exchange between vessels and brain, several molecules and inflammatory factors effect on the channel expressing on the surface of astrocytes and other main paths that could contribute to neuronal disorders. The article also includes several chemicals and their effects on inhibiting astrocytes of isolated sample, from chliroquine, calmodulin-trifluoperazin, gamma globulin and anticardiolipin antibodies. Last, the present study on the relationship between epilepsy and schizophrenia is discussed.

Primary Antiphospholipid Syndrome Presenting with Cerebellar Stroke and Positive Titres of Anti-β2 Glycoprotein-1 Antibody Only: A Case Report (P9-5.026)

<h3>Objective:</h3> To describe a case of Primary Antiphospholipid Syndrome presenting with Cerebellar Stroke and positive titres of anti-β2 glycoprotein-1 antibody only. <h3>Background:</h3> Antiphospholipid syndrome (APS) is an autoimmune disease where the presence of antiphospholipid antibodies leads to the development of arterial and/or venous thromboses and obstetric complications. Amongst the myriad of presentations, APS can manifest in the form of cerebrovascular stroke. However, overlapping clinico-radiological findings and a lack of classic APS features can sometimes pose a diagnostic dilemma. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 31-year-old female presented with occipital headache and difficulty in walking. Neurological examination revealed ataxia, dysdiadochokinesia and intention tremor. Preliminary laboratory findings revealed raised ESR along with normal CRP, aPTT and PT levels. MRI brain showed an acute infarct in the right cerebellar hemisphere and right postero-lateral upper medulla. MRA Head &amp; Neck revealed an occluded intracranial right vertebral artery with an extracranial segment showing multifocal occlusions with aorta and its major branches unaffected. These features and the absence of fever, rash, joint pain or obstetric complications led to the consideration of stroke due to Takayasu Arteritis. Treatment was initiated with corticosteroids, anticoagulants and antiplatelet drugs. However, on review of other laboratory tests, notably the auto-immune profile showed the presence of anti-ß2 glycoprotein-I antibodies with negligible titres of lupus anticoagulant and anti-cardiolipin antibody. This pointed towards a diagnosis of Primary Antiphospholipid Syndrome, which was confirmed after 12 weeks when repeat laboratory tests indicated the presence of IgM anti-ß2 glycoprotein-I antibodies. The patient is now on lifelong Warfarin therapy and is leading a symptom-free life. <h3>Conclusions:</h3> This case illustrates the potential of anti-β2 glycoprotein-1 antibody to cause a cerebellar stroke in the absence of other commonly involved antibodies. It also highlights the value of a holistic stroke workup. Recognition of APS is imperative for the timely administration of treatment and to prevent a recurrence. <b>Disclosure:</b> Mr. Shah has nothing to disclose. Mr. Shah has nothing to disclose. Dr. Nagrani has nothing to disclose.

Evaluation of Anticardiolipin Antibodies and Lupus Erythematosus Cell in Type 2 Diabetes Nigerian Population

Evaluation of Anticardiolipin Antibodies and Lupus Erythematosus Cell in Type 2 Diabetes Nigerian Population

Chorea as the Initial Manifestation of Antiphospholipid Syndrome (P9-5.020)

<h3>Objective:</h3> To discuss a rare case of chorea presenting as the initial manifestation of autoimmune disease. <h3>Background:</h3> Autoimmune chorea, including paraneoplastic, post-infectious, and idiopathic etiologies, is one of the leading causes of adult-onset chorea behind Huntington’s and vascular diseases.¹ In particular, in primary antiphospholipid syndrome (APS) and systemic lupus erythematosus, chorea is the initial manifestation of disease in 0.9 to 2% of cases.^1,2 <h3>Design/Methods:</h3> Verbal and written consent were obtained from the patient. <h3>Results:</h3> 73-year-old female with PMH of ITP, left MCA ischemic stroke, SDH, and DVT on anticoagulation who presented initially to ED with choreoathetoid movements starting 3 days prior to admission. History was unremarkable for triggering factor. Head imaging was unremarkable for acute intracranial process. B12, folate, TSH, electrolytes, RPR, serum copper, ANA, anti-dsDNA, SS-A, SS-B, Smith, and RNP antibodies negative. Lupus anticoagulant, β2 glycoprotein, and anti-cardiolipin antibodies positive. EEG unremarkable. Pelvic ultrasound negative. Genetic testing for Huntington’s negative. LP normal with exception of positive Coxsackie B1–B6 and A24 antibodies. After five-day course of IVIg, movements improved and she was discharged on no immunosuppression. Five weeks later, patient returned to ED with worsening of choreoathetoid movements. Repeat head CT again negative for acute pathology. Repeated spinal was unremarkable. Patient received Solumedrol 1g for four days with significant improvement in symptoms, and discharged on Prednisone 60 mg daily with recommendation to follow-up with rheumatology and neurology. On follow-up several months later, patient maintained on Prednisone 5 mg daily with no recurrence of choreoathetoid movements. <h3>Conclusions:</h3> While chorea is not the most commonly reported movement disorder in the context of autoimmune disease, it is often a delayed diagnosis, resulting in recurrent admissions and healthcare costs. Laboratory testing for autoimmune disorders should be included in the initial work-up of new-onset chorea to establish the diagnosis and properly treat as to prevent development of fulminant disease. <b>Disclosure:</b> Ms. Alayon has nothing to disclose. Mrs. Goodis has nothing to disclose. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eisai. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Feinberg has stock in Amarin. Stuart N. Kieran, MD has nothing to disclose. Dr. Wirkowski has nothing to disclose.

P163 Grey matter myelitis is a severe phenotype of myelitis in systemic lupus erythematosus: experience from a tertiary care hospital in south India over a decade

Abstract Background/Aims Myelitis is a severe yet rare manifestation of systemic lupus erythematosus (SLE). Literature on lupus myelitis is limited to case reports and series. Birnbaum et al. reported the largest series (n = 22) with two distinct phenotypes based on clinical and imaging findings with mechanistic and therapeutic implications. Further validation of these two subtypes is not reported to date. The objective of the study was to identify distinct phenotypes in lupus myelitis and compare activity and outcomes with the formulation of a prediction model for survival. Methods This is a retrospective study. Data of 35 lupus myelitis patients with follow-up were extracted from the lupus registry (n = 1550) in the last 15 years (2007-2022). Grey matter myelitis (GMM) (i.e., flaccidity, hyporeflexia) and white matter myelitis (WMM) (i.e., spasticity, hyperreflexia) were two subtypes. Disease activity was assessed by SLEDAI-2K and outcome by death/recurrence/disability - modified Rankin score (MRS). MRS at discharge and SLEDAI at admission were used as predictors for survival outcomes among subtypes. Results Median age at presentation was 24.5 years (12.5-36.5); female-male ratio 32:3. 24 patients presented with GMM and 11 with WMM. GMM had more CNS events (p-0.02), high SLEDAI (p-0.021) and extra CNS involvement (p &amp;gt; 0.05). Anticardiolipin antibodies were increased in WMM (p-0.03). Weibull survival probability plot showed that 25%, 50% &amp; 75% of GMM patients had probability of death within 13, 85, and 376 months from the myelitis episode respectively. The same for WMM was 96, 256, 556 months respectively, implying that GMM has a worse survival outcome. Using linear regression, MRS at discharge and SLEDAI can predict survival status in GMM (R = 0.64, p = 0.04) but not in WMM (R = 0.42, p = 0.46). Conclusion Lupus myelitis has two distinct subtypes. GMM is associated with more active disease, poor survival, and significant disability, and its survival status can be predicted by MRS and SLEDAI scores. Disclosure R. Baisya: None. K. Yerram: None. G. Murthy: None. P.K. Devarasetti: None. L. Rajasekhar: None.

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.

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.

Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a typical chronic immune disorder with clinical heterogeneity. The systemic abnormal immune response not only challenges the diagnosis and treatment of the disease itself but also the secondary antiphospholipid syndrome (APS), characterized by recurrent arterial or venous thrombosis, recurrent spontaneous abortion, or stillbirth. Clinical interest has primarily focused on primary APS's pathological and clinical features. However, differences in clinical features and laboratory indicators between SLE with or without APS are still lacking, especially differences between circulating lymphocytes, which are critical in the pathogenesis of SLE and its complications. In this retrospective study, we collected and analyzed clinical characteristics, general laboratory indicators, immunological indicators, and circulating lymphocyte subsets of SLE with or without APS. Systemic lupus erythematosus with APS (SLE-APS) had elevated SLEDAI scores, hospitalization costs and time, and frequencies of central nervous system symptoms and spontaneous abortion compared with those without APS. SLE-APS had higher positive anti-Cardiolipin antibodies, anti-β2 Glycoprotein 1 antibodies, and perinuclear antineutrophil cytoplasmic antibody (pANCA) than none-APS patients. Compared with healthy controls (HCs), the circulating lymphocyte subsets were altered to some extent in all patients, especially in patients with SLE-APS. Reduced Tregs and positive pANCA were independent risk factors for SLE secondary APS. The present study revealed a robust association between APS secondary to SLE and reduced Tregs and positive pANCA, which provides essential information regarding the diagnosis and therapeutic possibilities of APS secondary to SLE.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study

Several antiphospholipid antibody (aPL) profiles (“triple” and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-β2 glycoprotein-I antibody (aβ2GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aβ2GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aβ2GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aβ2GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001). Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

Metastasis-associated lung adenocarcinoma transcript 1 induces methyl-CpG-binding domain protein 4 in mice with recurrent spontaneous abortion caused by anti-phospholipid antibody positivity

IntroductionAntiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA. MethodsClinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells. ResultsMALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1. DiscussionMALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region.

New-onset giant cell arteritis with lower ESR and CRP level carries a similar ischemic risk to other forms of the disease but has an excellent late prognosis: a case-control study.

Biopsy-proven giant cell arteritis (GCA) occasionally presents without acute-phase reaction. In this setting, GCA may be initially overlooked and glucocorticoid treatment unduly delayed, potentially increasing ischemic risk. From an inception cohort of patients with newly diagnosed, biopsy-verified GCA, we retrieved all cases without elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level before starting glucocorticoid treatment. We compared the baseline features and outcomes of these patients and two additional patients recruited after GCA diagnosis with those of 42 randomly selected patients with high baseline ESR and CRP. Of 396 patients, 14 (3.5%) had lower baseline values of both ESR and CRP. Lower baseline ESR and CRP were associated with fewer American College of Rheumatology criteria met (p < 0.001, 95% CI -1.1; -0.9), and less jaw claudication (p = 0.06, 95% CI 0.8; 44.9), but similar rates of permanent blindness (p = 1.0). Patients with lower ESR and CRP also showed obvious differences regarding mean blood cell counts and mean hemoglobin level, but also less anti-cardiolipin antibody positivity (p = 0.04, 95% CI 0.8; ∞) and hepatic cholestasis (p = 0.03, 95% CI 1.0; 422). Patients with lower ESR and CRP had fewer GCA relapses (p = 0.03, 95% CI -1.1; -0.1), fewer glucocorticoid-induced complications (p = 0.01, 95% CI -2.0; -0.1), and successfully stopped glucocorticoids sooner than the other patients (18.3months vs 34months in average, p = 0.02, 95% CI -27;-0.9). Biopsy-proven GCA presenting with lower ESR and CRP is not an exceptional occurrence. It is clinically less typical but carries similar ischemic risk to other forms of the disease. Conversely, the late GCA prognosis of these patients is excellent.

ANTENATAL DIAGNOSIS OF FETAL HEART RHYTHM DISORDERS IN WOMEN WITH LUPUS WITH POSITIVE ANTI-SSA AND ANTI-SSB ANTIBODIES: ABOUT TWO CASES

Lupus erythematosus is a nonorgan-specific autoimmune disease predominantly affecting young women of childbearing age, as well as neonatal lupus is a complication related to the presence of anti-SSA/Ro or anti-SSb/La antibodies in the mother. Cardiac manifestations of neonatal lupus include anti-SSA/Ro-SSB/La-mediated conduction system disease and endocardial/myocardial damage resulting in cardiomyopathy. Pregnancy is a complicating factor in lupus erythematosus in 60% of cases. These complications do not seem to be related to the number of pregnancies or to the duration of remission, but stopping the hydroxychloroquine treatment could be the cause of relapses. Obstetrical complications due to lupus are dominated by intrauterine growth retardation and prematurity in 30% of cases, abortion or fetal death in utero in 20% of cases, especially in the presence of anti-phospholipid antibodies and/or anti-cardiolipin antibodies in the mother, and complete atrioventricular block in 1.6% of cases due to trans-placental passage of anti-SSA antibodies. Some treatments, including hydroxychloroquine, corticosteroids, and certain immunosuppressants (azathioprine) are safe, and can and should be maintained if necessary during pregnancy.

Anticardiolipin Antibodies in Patients with Cancer: A Case–Control Study

Antiphospholipid antibodies are highly prevalent in autoimmune diseases and mainly associated with thromboembolic events, which is one of the major reasons for cancer-related mortality. Confirmed adult cancer patients were included (n = 40) with an equal number of age- and sex-matched healthy controls. The presence and concentration of anticardiolipin antibodies were investigated by the enzyme-linked immunosorbent assay using the venous blood samples. aCL antibodies were detected in 60.0% (n = 24) of the cancer patients compared to none in the healthy controls (p < 0.001). The serum concentration of aCL antibodies was significantly higher in cancer patients than controls (p < 0.001) and ranged from 89.0 U/mL to 133.0 U/mL among the aCL-positive patients. All the lung cancer patients (n = 6) were diagnosed with positive aCL, and a borderline significant association of aCL antibody positivity was observed in colon cancer patients (p = 0.051). About 72.7% of the advanced-stage cancer individuals and 81.8% of the cancer patients who underwent surgery were diagnosed with positive aCL antibodies. A significant association of aCL antibody positivity was observed with cancer patients comorbid with heart diseases (p = 0.005). The prevalence and serum levels of aCL antibodies were significantly higher in cancer patients compared to healthy controls. Cancer patients (i.e., lung, liver, and colon), at advanced-stage, comorbid with heart diseases, who underwent surgery, were more likely to be diagnosed with aCL antibodies.

Relations between antinuclear, antineutrophil cytoplasmic, anticardiolipin antibodies and degree of neurological deficit, cerebrovascular stenosis in cerebral infarction patients.

To investigate the correlation of antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (ACA) with the degree of the neurological defect and cerebrovascular stenosis in patients with cerebral infarction. Clinical data of 99 patients with acute cerebral infarction (ACI) admitted to the Department of Neurology of Baoding First Central Hospital from June 2020 to December 2021 were retrospectively analyzed, and their ANA, ACA, ANCA, neurological deficit (NIHSS) scores as well as cerebrovascular stenosis were detected and assessed. Moreover, the correlation between the positive expression rates of ANA, ANCA, ACA and the degree of the neurological deficit, as well as the location and degree of cerebrovascular stenosis, were analyzed. All patients had ANA, ACA, ANCA antibodies with positive rates of 68.69%, 70.71%, 69.70%, and mild, moderate, and severe cerebrovascular stenosis with incidence rates of 28.28%, 32.32%, and 39.39% respectively; Moreover, their incidence of mild, moderate, and severe neurological deficits were 15.15%, 44.44%, and 40.40%, respectively. Statistically significant differences could be observed in the degree of cerebrovascular stenosis and neurological deficit between the ANA, ACA and ANCA antibody positive group and the negative group (p<0.05). ANA, ACA, ANCA antibody positive was moderately positively correlated with cerebrovascular stenosis rate and NIHSS score (0.40<r<0.60, p<0.05). The positive rates of ANA, ACA and ANCA antibodies were higher in patients with ACI, which was closely correlated with the degree of cerebrovascular stenosis and neurological deficit.

Post-COVID musculo-articular syndrome and COVID-19 association with rheumatoid arthritis

Introduction. Since the COVID-19 pandemic, there has been a great deal of evidence for a variety of post-COVID symptoms, including the presence of a musculo-articular syndrome. The aim of the study was to analyze the current literature data on the prevalence of musculo-articular syndrome and to study the association of coronavirus infection with the development of rheumatoid arthritis. Materials and methods. We searched PubMed, Medline, and Google Scholar (2020-2022) for articles using the following keywords: post-covid syndrome, muscular articular syndrome or muscle and joint pain, COVID-19, SARS-CoV-2, rheumatoid arthritis. We found 622 articles in which these words appeared in the text of the article. Further, 497 articles were excluded as irrelevant to the topic of the study. During the study of the remaining articles, special attention was paid to the occurrence of musculo-articular syndrome after COVID-19 infection and the association with rheumatoid arthritis. Results and discussion. There are studies describing musculo-articular pain syndrome and cases of antibodies to cyclic citrullinated peptide (ACCP) after COVID-19, which may indirectly indicate the development of rheumatoid arthritis in these patients. Studies reflect the increased autoreactivity of the immune system in COVID-19, consisting in increased titers of antinuclear antibodies, anti-cardiolipin antibodies, ACCP, and rheumatoid factor. A number of articles have presented results on the association between COVID-19 infection and the appearance, or exacerbation, of rheumatoid arthritis. Several mechanisms are discussed, presumably leading to the occurrence of post-COVID rheumatoid arthritis: induction by coronavirus of excess synthesis of angiotensin II, which increases the expression of inflammatory cytokines, chemokines and production of reactive oxygen species; activation of proinflammatory T-cell subpopulations; activation of Toll-like receptor-7 synovial membrane triggering the inflammatory response; "cytokine storm". Conclusion. A high percentage (from 15 to 47.7 %) of cases of musculo-articular lesions after COVID-19 infection has been identified. A number of articles have reported an association between COVID-19 infection and the onset, or exacerbation, of rheumatoid arthritis, but the issue is still under discussion, which necessitates large-scale studies specifically devoted to examining this association.

Antiphospholipid Syndrome and Pregnancy

Antiphospholipid syndrome is an autoimmune disease with a wide spectrum of manifestations from different organs, therefore it is challenging to diagnose. The disease presents antiphospholipid antibodies such as anticardiolipin antibodies (aCL), lupus anticoagulant (LA) and antiβ2-glycoprotein 1 antibodies (β2GPI). The most common symptoms include thrombosis in veins and arteries and obstretical complications such as early miscarriage, intrauterine fetal death, intrauterine growth restriction (IUGR), placental insufficiency, premature labor and eclampsia. To diagnose a patient with APS certain criteria have been chosen, where at least one clinical and one laboratory criterion must be present. In many cases it takes a lot of time before a proper diagnosis has been made, when a female patient presents obstretical complications. Adequate pharmacological treatment increases the odds of live birth rate from 20-30% to 70-80%. Scientific research shows correlation between antiphospholipid syndrome, infertility and premature ovarian insufficiency. Treatment mostly consists of heparin and low-dose aspirin, in certain cases hydrochloroquine is prescribed. Aside from pharamcological therapy, it is very important to minimize the effects of modifiable risk factors. The following article focuses on complications, diagnosing and therapy in pregnant women suffering from Antiphospholipid syndrome. All sources can be found in Pubmed’s website database.

Huge water-balloons in the belly: multiple pancreatic pseudocysts in systemic lupus erythematosus.

A 28-year-old woman presented with recurrent epigastric pain and abdominal distention for 6 months. Her symptoms first occurred on the first day of admission due to SLE flare (fever, polyarthritis, anaemia, leukocytopenia, proteinuria, low C3, positive tests on antinuclear, anti-double-stranded DNA, anti-Smith and anti-cardiolipin antibodies), when no treatment was initiated. Elevated blood amylase and CT (Fig. 1A) indicated acute pancreatitis and other common causes were excluded. Thrombotic microangiopathy (TMA) was then suspected because of renal, neuropsychiatric and haematological involvements. However, abdominal distention and peripancreatic effusions perpetuated though SLE, TMA and secondary infection remitted after using glucocorticoid, immunosuppressive agents, plasma exchange and supportive therapies. Therefore, drainage was performed a month before this presentation and CT (Fig. 1B) showed improvement. During this admission, emergency drainage was performed due to reappearing ascites. Analysis of chylous ascites identified extremely elevated amylase and lipase with Enterococcus faecium as pathogen. Massive ascites were encapsulated with a fistula connected to the newly emerged pseudocyst (Fig. 1C and D). Drainage was not removed until radiographic remission 7 months later (Fig. 1E). SLE flare and abdominal symptoms have not occurred up to the last follow-up 41 months after this admission. This case illustrates SLE-associated acute pancreatitis can present with atypical features [1, 2] and prolonged courses due to ‘add-on’ effects of SLE flare, infection, coagulopathy (thrombocytopenic purpura, antiphospholipid syndrome) and medication. Therefore, a tailored management strategy is required.

Risk factors for persistent positive anticardiolipin antibodies in women with recurrent pregnancy loss

Antiphospholipid syndrome (APS) is an established cause of recurrent pregnancy loss (RPL). It is necessary to detect persistently positive antiphospholipid antibodies to diagnose APS. This study aimed to explore risk factors for persistent anticardiolipin (aCL) positivity. Women with a history of RPL or with a history of one or more intrauterine fetal deaths after 10 weeks underwent examinations to determine the causes of RPL, including antiphospholipid antibodies. If aCL-IgG or aCL-IgM antibodies were positive, retests were performed at least 12 weeks apart. Risk factors for persistent aCL antibody positivity were retrospectively investigated. The number and percentage of cases above the 99th percentile were 74/2399 (3.1%) for aCL-IgG, and 81/2399 (3.5%) for aCL-IgM. Of the initially tested cases, 2.3% (56/2399) for aCL-IgG and 2.0% (46/2289) for aCL-IgM were ultimately positive above the 99th percentile in retests. Retest values after 12 weeks were significantly lower than the initial values for both IgG and IgM immunoglobulin classes. Initial aCL antibody titers were significantly higher in the persistent-positive group than in the transient-positive group for both IgG and IgM immunoglobulin classes. The cut-off values for predicting persistent positivity of aCL-IgG antibodies and aCL-IgM antibodies were 15 U/mL (99.1 percentile) and 11 U/mL (99.2 percentile), respectively. The only risk factor for persistently positive aCL antibodies is a high antibody titer during the initial test. When the aCL antibody titer in the initial test exceeds the cut-off value, therapeutic strategies can be defined in subsequent pregnancies without waiting for 12 weeks.

A rare presentation of primary apla and pulmonary thrombolism

Antiphospholipid syndrome (APS) is a state of hypercoagulation, causing thrombus in artery, vein and capillaries, with or without obstetrical events with the presence of autoantibodies, which includes lupus anticoagulant, anticardiolipin antibodies and anti-β2-glycoprotein 1 antibodies. It has variable clinical presentations such as vascular thrombosis and obstetrical complications, pulmonary thromboembolism (PTE), pulmonary hypertension, and acute respiratory distress syndrome. Hereby we presented a case of young male who came to our hospital with hemoptysis and isolated pulmonary embolism, with the background of APS which is rare. Hemoptysis and pulmonary thromboembolism both being fatal emergencies requiring completely different management methods.