Anticardiolipin Antibody Titers Research Articles

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Abstract Background Comparing cases of adult onset and late onset systemic lupus erythematous (SLE) reveals significant differences in clinical, serological, disease activity, and damage score. Objective This study aimed to analyze clinical manifestations, laboratory data, serological markers, and prognosis of late-onset SLE (L-SLE) and for comparing with adult- onset SLE. Patients and Methods One hundred fifty individuals with SLE were included in a cross-sectional study conducted at Ain Shams University Hospital divide into Group 1: 100 cases with adult-onset (age of onset ≥ 19 years and below 50 years). Group 2: 50 Patients with L-SLE (age of onset ≥ 50 years). All patients were subjected to medical history, physical examination, disease activity measured by the SLE disease activity index (SLEDAI-2K) and a damage score. Laboratory investigations as complete blood count (CBC), serum creatinine, anticardiolipin antibodies, lupus anticoagulant, protein creatinine ratio, serum complement (C3, C4), anti-dsDNA antibody, and antinuclear antibodies (ANA). Results Mucocutaneous manifestations, frequency of hematuria, proteinuria, urinary cast, consumed C3, positive anti-dsDNA antibodies, anti-cardiolipin antibody and lupus anticoagulant titers had considerably greater rates in-group 1 compared to group 2 (P-value <0.05) while group 2 had significantly more musculoskeletal symptoms (P-value <0.05). The SLEDAI scores of the two groups were equivalent, however the damage index was greater in group 2 (P-value 0.00). Neuropsychiatric, cutaneous, renal, and skin damage were more frequent in group 1, while musculoskeletal, endocrinal, pulmonary, cardiovascular and ocular damage were more frequent in- group 2. Conclusion L-SLE is different from adult onset SLE with more frequent damage.

IgA is the predominant isotype of anti-β2 glycoprotein I in patients with COVID-19.

The aim of this research was to determine the frequency of antiphospholipid antibodies (aPL) in patients with COVID-19. The frequency and titers of anticardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) were determined in sera of adult patients hospitalized with COVID-19. Immunoglobulin (Ig)G, IgA, IgM aCL, and aβ2GPI were measured using enzyme-linked immunosorbent assay. Eighty-three patients were included in the study. The mean age of patients was 62 ± 13.9 years, ranging from 23 to 86 years. Stratification according to severity of infection divided patients in 2 groups: 45 patients with moderate infection and 38 patients with critical or severe infection. Out of the 83 patients suffering from COVID-19, aPL (aCL or aβ2GPI) were detected in 24 patients (28.9%). IgG, IgA and IgM aβ2GPI were positive in 2.4%, 16.9% and 8.4%, respectively. IgG, IgA and IgM aCL showed positivity in 7.2%, 0%, and 4.8%, respectively. The frequency of aPL was 36.8% in patients with critical/severe infection and 22.2% in patients with moderate infection. In critical/severe patients, the frequency of aβ2GPI was significantly higher than aCL (34.2% vs 13.2%, P = .03) and aβ2GPI-IgA were significantly more frequent than aβ2GPI-IgG (21.1% vs 2.6%, P = .028). In this cross-sectional study, aPL and particularly aβ2GPI-IgA were common in patients with COVID-19.

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.

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center

To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-β2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Anzi Heji Downregulates DNMT1 to Improve Anticardiolipin Antibody (ACA)-Positive Abortion by Regulating JAK/STAT Pathway

Anzi Heji (AZHJ) is a traditional Chinese medicine compound prepared for long-term treatment of Anticardiolipin Antibody (ACA)-positive abortion, with small side effects and definite curative effect. Abortion was reported to be related to DNMT1, a methylation transferase regulated by JAK2 pathway, so this study aimed to explore whether AZHJ treated ACA-positive abortion by regulating the DNMT1. Cell proliferation estimation employed Cell counting kit-8 (CCK-8) and flow cytometry. Human β2-glycoprotein I (GPI) was used as an inducer to establish ACA-positive mice model. Western blot was applied to examine the expressions of DNMT1, FOXP3, IL-6, and JAK/STAT3 pathway-related proteins. ACA titers and IL-6 levels in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). Placental tissue damage was assessed by hematoxylin and eosin (H&amp;E) staining. Based on the findings from experiments, AZHJ could significantly inhibit apoptosis and regulate the proliferation activity of HTR-8/SVneo cells. AZHJ treatment reduced the expression levels of DNMT1, FOXP3, IL-6, and JAK/STAT3 signaling pathways-related proteins in HTR-8/SVneo cells and maternal–fetal interface (uterine decidua and placenta), and the titer of serum ACA was also significantly decreased. In addition, AZHJ effectively alleviated placental tissue damage caused by ACA-positive abortion compared with model group. To sum up, AZHJ may play a therapeutic role by inhibiting DNMT1 activation through Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and then promoting FOXP3 expression in maternal–fetal interface of pregnant mice, thereby improving immune tolerance at the maternal–fetal interface, preventing and treating ACA-positive abortion.

Hypercoagulability in patients with indirect carotid cavernous fistulas.

To assess patients with indirect carotid-cavernous fistulas (CCF) for evidence of hypercoagulable state (HS) by combination of comprehensive medical questionnaire and laboratory testing. Patients with confirmed diagnosis of CCF treated between 2003 and 2019 were included and administered a questionnaire screening for HS risk factors and undergone laboratory investigations which included complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody titres), Factor V Leiden, prothrombin, protein C, protein S, antithrombin III, homocysteine, prothrombin G20210, CALR and JAK2 mutation screening. Participants with abnormal laboratory testing and/or past history of ischemic stroke, atrial fibrillation, cancer or hypercoagulability-associated hereditary disorders were deemed to have HS. Twenty-two patients were enrolled. Seventeen were women and the mean age at diagnosis was 60. Fourteen (64%) had evidence of HS: six on medical history, three with laboratory evidence and five with both. Eight (36%) had current abnormal hypercoagulability markers. One had a diagnosis of Klippel-Trenaunay Syndrome, but no others had evidence of hereditary thrombophilia. Nine were on anti-coagulation initiated after diagnosis of stroke or atrial fibrillation discovered on average 5.5 years after the diagnosis of CCF. A total of 64% percent of patients with previous indirect CCF had evidence of underlying HS indicating that hypercoagulability might play a role in the pathogenesis of CCF. The results support need for comprehensive testing for underlying HS in patients with indirect CCFs to better identify, manage, and prevent further thromboembolic events.

Correlation Analysis of Anti-Cardiolipin Antibody/D Dimer/C-Reactive Protein and Coronary Artery Lesions/Multiple-Organ Damage in Children With Kawasaki Disease.

Aim: Kawasaki disease (KD) is a systemic vasculitis with unknown etiology. In addition to cardiovascular system involvement, it can also have other multiple organs involved. This study is aimed at investigating the correlation between anti-cardiolipin antibody (ACA)/D dimer/C reactive protein (CRP) and coronary artery lesions (CAL)/multiple-organ lesions in children with KD.Methods: Retrospective analysis was performed in 284 KD/IKD patients from May 2015 to April 2016. Among them, 175 were males (61.6%), with average age of 2 years and 5 months old. Patients were divided into ACA+ group and ACA- group, elevated D dimer group (DDE) and normal D dimer group (DDN), and coronary artery injury (CAL) group and non-coronary artery injury (NCAL) group.Results: ACA was most likely tested positive in younger KD children (p < 0.05). ACA+ and hypoproteinemia were correlated with CAL, thrombocytosis, and granulocytopenia (p < 0.05–0.01). Levels of cTnI and CK in the CAL group were significantly higher than those in the NCAL group (p < 0.05). CAL was more frequently detected in younger patients and patients with prolonged fever, later IVIG treatment, and elevated CRP over 100 mg/l, but there was no statistically significant difference (all p > 0.05). In the KD with DDE group, the incidence of granulopenia, thrombocytosis, myocardial damage, cholestasis, hypoproteinemia, and aseptic urethritis was significantly higher than that in the KD with DDN group (p < 0.05–0.01). However, elevated D dimer was not associated with CAL. CRP elevation was highly correlated with D dimer, but not with CAL.Conclusion: Higher incidence of CAL and myocardial damage occurred in KD patients with positive ACA and hypoproteinemia. In the current study, ACA was only tested for positive and negative, which is a limitation to this study. To further elucidate the association, ACA titers would establish its significance in drawing a conclusion for the significance of ACA in CAL and myocardial damages. In addition, higher incidence of CAL occurred in younger patients. The higher D dimer was associated with increased multiple-organ damage (MOD). CRP was closely correlated with D dimer, but not correlated with ACA and CAL.

O-002. Beneficial Role of sodium nitrate on pregnancy in mice lacking eNOS

To report a series of patients with occlusive retinal vasculitis associated with systemic sclerosis (SSc) and elevated antiphospholipid antibody titers.Case series. Main outcome measures included clinical and fluorescein angiographic findings at presentation and over time.Case 1 - A 61-year-old woman initially diagnosed with idiopathic, bilateral panuveitis and retinal vasculitis causing peripheral nonperfusion was subsequently diagnosed with limited cutaneous systemic sclerosis (lcSSc). Her ocular inflammation and retinal vasculitis were controlled with topical and periocular corticosteroids, but she eventually developed peripheral retinal vascular occlusion that progressed to macular ischemia 11 years after presentation. Repeat serologic evaluation detected interval development of antiphospholipid antibodies. Case 2 – A 58-year-old woman was found to have bilateral peripheral nonperfusion and retinal neovascularization in her right eye. Given her elevated hemoglobin A1c of 8.5%, she was diagnosed with presumed proliferative diabetic retinopathy. Three years after initial presentation, she was diagnosed with lcSSc. Subsequent serum workup detected elevated B2-glycoprotein antibody titers. Her peripheral nonperfusion progressed despite adequate glycemic control, resulting in further neovascularization in each eye. Case 3 – A 40-year-old woman with diffuse cutaneous systemic sclerosis (dcSSc) and elevated titers of anti-cardiolipin antibodies developed multiple branch retinal artery occlusions with subsequent neovascularization of the retina, optic disc, and angle in the right eye.Vision-threatening occlusive retinal vasculitis may develop in select patients with SSc. The presence of elevated anti-phospholipid antibody titers may confer increased risk for this vision-threatening complication.

P-018. Analysis of subpopulation of exosomes in prospective samples before the onset of preeclampsia

To report a series of patients with occlusive retinal vasculitis associated with systemic sclerosis (SSc) and elevated antiphospholipid antibody titers.Case series. Main outcome measures included clinical and fluorescein angiographic findings at presentation and over time.Case 1 - A 61-year-old woman initially diagnosed with idiopathic, bilateral panuveitis and retinal vasculitis causing peripheral nonperfusion was subsequently diagnosed with limited cutaneous systemic sclerosis (lcSSc). Her ocular inflammation and retinal vasculitis were controlled with topical and periocular corticosteroids, but she eventually developed peripheral retinal vascular occlusion that progressed to macular ischemia 11 years after presentation. Repeat serologic evaluation detected interval development of antiphospholipid antibodies. Case 2 – A 58-year-old woman was found to have bilateral peripheral nonperfusion and retinal neovascularization in her right eye. Given her elevated hemoglobin A1c of 8.5%, she was diagnosed with presumed proliferative diabetic retinopathy. Three years after initial presentation, she was diagnosed with lcSSc. Subsequent serum workup detected elevated B2-glycoprotein antibody titers. Her peripheral nonperfusion progressed despite adequate glycemic control, resulting in further neovascularization in each eye. Case 3 – A 40-year-old woman with diffuse cutaneous systemic sclerosis (dcSSc) and elevated titers of anti-cardiolipin antibodies developed multiple branch retinal artery occlusions with subsequent neovascularization of the retina, optic disc, and angle in the right eye.Vision-threatening occlusive retinal vasculitis may develop in select patients with SSc. The presence of elevated anti-phospholipid antibody titers may confer increased risk for this vision-threatening complication.

English

BACKGROUND Anticardiolipin antibodies (aCL) have been recognized as an independent risk factor for an increased risk of thrombosis. The aim of our study was to assess the prevalence of aCL antibodies in patients with CVT (Cerebral Venous Thrombosis) and correlate clinical profile of CVT with anticardiolipin antibody titre. METHODS Forty-two patients with CVT diagnosed by neuroimaging were investigated for the presence of aCL. We compared the clinical profile of ACL antibody positive and negative group. RESULTS Anticardiolipin antibodies were detected in 30.9 % of CVT patients. In anticardiolipin antibody negative group, mean age was 26.76 ± 8.49 years, compared to positive group in which mean age was 32.00 ± 10.88 years which was statistically not significant. In our study, mean leukocyte count was low among aCL positive group compared to negative group (8396 ± 2694.8 vs. 10472.41 ± 3353.5), which was statistically not significant. Both positive and negative groups were comparable with respect to other clinical findings. CONCLUSIONS Anticardiolipin antibodies (aCL) have been recognized as an independent risk factor for an increased risk of thrombosis. Its presence in patients with CVT requires lifelong anticoagulation to prevent recurrence. So all patients of CVT need to be evaluated for the presence of anticardiolipin antibodies. KEYWORDS Cerebral Venous Thrombosis, CVT, Anticardiolipin Antibodies

Incidence of Antithrombin Deficiency and Anti-Cardiolipin Antibodies After Severe Traumatic Brain Injury: A Prospective Cohort Study.

Animal studies suggested that cerebral mitochondrial cardiolipin phospholipids were released after severe traumatic brain injury (TBI), contributing to the pathogenesis of thromboembolism. To determine the incidence of anti-cardiolipin antibodies after severe TBI and whether this was related to the severity of TBI and development of venous thromboembolism. Serial anti-cardiolipin antibodies, antithrombin levels, viscoelastic testing, and coagulation parameters were measured on admission, day-1, and between day-5 and day-7 in patients with severe TBI requiring intracranial pressure monitoring. Of the 40 patients included (85% male and median age 42years), 7 (18%) had a raised Ig-G or Ig-M anti-cardiolipin antibody titer after TBI. Antithrombin levels were below the normal level-especially on day-0 and day-1-in 15 patients (38%), and 14 patients (38%) developed an increase in maximum clot firmness on the viscoelastic test in conjunction with elevations in fibrinogen concentration and platelet count. Four patients (10%) developed deep vein thrombosis, and 10 patients (25%) died, both of which were not significantly related to the presence of anti-cardiolipin antibodies (P = 0.619 and P = 0.638, respectively). A reduction in antithrombin level and development of anti-cardiolipin antibodies were not rare immediately after severe TBI; these abnormalities were followed by an increase in in vitro clot strength due to elevations in fibrinogen concentration and platelet count. The quantitative relationships between the development of anti-cardiolipin antibodies and severity of TBI or clinical thromboembolic events deserve further investigation.

An invitro model to mimic the thrombotic occlusion of small vessels in catastrophic antiphospholipid syndrome (CAPS).

Platelet activation and decrease in platelet count characterize the development of the most feared form of antiphospholipid syndrome (APS), i.e. catastrophic APS (CAPS). We aimed to assess if immuno-affinity purified anti-β2-glycoprotein I (aβ2GPI) antibodies enhance platelet activation inducing a significant flow obstruction in a platelet function analyzer (PFA). Affinity purified aβ2GPI antibodies were obtained from 13 triple positive patients with a strong lupus anticoagulant (LA) and high titers of IgG anticardiolipin antibodies (aCL) and IgG aβ2GPI. Platelet activation stimulated by adenosine diphosphate (ADP) in the presence or absence of aβ2GPI was measured by the expression of P-selectin on platelet surface using flow cytometry. P-selectin expression remained close to baseline when normal whole blood was incubated with aβ2GPI alone. When stimulated using aβ2GPI combined with ADP, P-selectin expression (28.42 ± 5.15% vs. 20.98 ± 3.94%, p = 0.0076) was significantly higher than ADP alone. Closure time of normal whole blood passed through the PFA was significantly shorter using affinity purified aβ2GPI than control IgG both in Col/ADP (160.1 ± 62.1 s vs. 218.6 ± 43.8 s; p = 0.021) and Col/EPI cartridges (149.5 ± 26.7 s vs. 186.9 ± 45.5 s; p = 0.030). Thus, platelet activation is enhanced by aβ2GPI antibodies with a consequent premature closure in a PFA, possibly resembling that in microcirculation in patients with CAPS.

Case report presenting the diagnostic challenges in a patient with recurrent acquired angioedema, antiphospholipid antibodies and undetectable C2 levels

BackgroundAngioedema secondary to acquired C1 inhibitor deficiency (AAE) is a rare disease. It usually is associated with lymphoproliferative disorders. We present a case of AAE in a patient with antiphospholipid syndrome (APS), a non-Hodgkin lymphoproliferative disorder (NHL) with undetectable levels of C2, C4, and an undetectable CH50. The co-existence of AAE, APS, and NHL, with an undetectable C2 level, to the best of our knowledge, has never before reported together in the same patient.Case presentationA patient with a recent history of thrombosis presented with recurrent episodes of angioedema. The workup revealed undetectable levels of C2, C4 and undetectable CH50. Quantitative levels of C1 inhibitor and C1q were low. C1 inhibitor function was less than 40%. Anti-cardiolipin antibodies were found. The patient was initially treated on demand with intravenous plasma-derived human C1-INH concentrates, (Cinryze® Shire). Later the patient received prophylactic therapy with danazol. She was diagnosed with lymphoma 3 years after her first episode of angioedema. Single agent therapy with rituximab was not only effective in treating her lymphoma but also preventing further episodes of angioedema. Anti-cardiolipin antibody titers also declined. Additionally, marked early primary pathway complement component abnormalities and CH50 also corrected, although incomplete normalization of C4 proved to be due to a heterozygous C4 deficiency.ConclusionThis case shows the unique association of AAE, APS and NHL in a patient with undetectable levels of early complement components. Additionally, this case also shows for the first time the effectiveness of rituximab therapy in all three disease states while co-existing simultaneously in the same patient.

Risk Assessment and Management of Venous Thromboembolism in Women during Pregnancy and Puerperium (SAVE): An International, Cross-sectional Study.

The clinical burden of obstetric venous thromboembolism (VTE) risk is inadequately established. This study assessed the prevalence and management of VTE risk during pregnancy and postpartum outside the Western world. This international, noninterventional study enrolled adult women with objectively confirmed pregnancy attending prenatal care/obstetric centers across 18 countries in Africa, Eurasia, Middle-East, and South Asia. Evaluations included proportions of at-risk women, prophylaxis as per international guidelines, prophylaxis type, factors determining prophylaxis, and physicians' awareness about VTE risk management guidelines and its impact on treatment decision. Data were analyzed globally and regionally. Physicians ( N = 181) screened 4,978 women, and 4,010 were eligible. Of these, 51.4% were at risk (Eurasia, 90%; South Asia, 19.9%), mostly mild in intensity; >90% received prophylaxis as per the guidelines (except South Asia, 77%). Women in Eurasia and South Asia received both pharmacological and mechanical prophylaxes (>55%), while pharmacological prophylaxis (>50%) predominated in Africa and the Middle-East. Low-molecular-weight heparin was the pharmacological agent of choice. Prophylaxis decision was influenced by ethnicity, assisted reproductive techniques, caesarean section, and persistent moderate/high titer of anticardiolipin antibodies, though variable across regions. Prophylaxis decision in at-risk women was similar, irrespective of physicians' awareness of guidelines (except South Asia). A majority (>80%) of the physicians claimed to follow the guidelines. More than 50% of women during pregnancy and postpartum were at risk of VTE, and >90% received prophylaxis as per the guidelines. Physicians are generally aware of VTE risk and comply with guidelines while prescribing prophylaxis, although regional variations necessitate efforts to improve implementation of the guidelines.

Efficiency of immunosuppressive therapy in virus-negative and virus-positive patients with morphologically verified lymphocytic myocarditis

To evaluate the efficiency of immunosuppressive therapy (IST) in virus-negative (V-) and virus-positive (V+) patients with lymphocytic myocarditis (LM). 60 patients (45 males) (mean age 46.7±11.8 years) with dilated cardiomyopathy (mean left ventricular (LV) end diastolic size (EDS) 6.7±0.7 cm; ejection fraction (EF) 26.2±9.1%) were examined. The diagnosis of active/borderline LM was verified by right ventricular endomyocardial biopsy in 38 patients, by intraoperative LV biopsy in 10, in the study of explanted hearts from 3 patients and at autopsy in 9. The investigators determined the genomes of parvovirus B19, herpes viruses types 1, 2 and 6, Epstein-Barr (EBV), zoster, and cytomegalovirus in the blood and myocardium and, if antibodies were present in the blood, hepatitis B and C viruses, as well as antibodies against antigens in the endothelium, cardiomyocytes and their nuclei, smooth muscles, fibers of the conducting system. IST was used in terms of histological, immune, and viral activities. IST was performed in 22 V+ patients (Group 1) and in 24 V- patients (Group 2); this was not done in 10 V+ patients (Group 3) and V- patients (Group 4). IST comprised methylprednisolone at a mean dose of 24 mg/day (n=40), hydroxychloroquine 200 mg/day (n=20), azathioprine at a mean dose of 150 mg/day (n=21); antiviral therapy included acyclovir, ganciclovir, intravenous immunoglobulin (n=24). The follow-up period was 19 (7.3-40.3) months. The viral genome was detected in the myocardium of 32 patients who made up a V+ group. The degree of histological activity did not differ in relation to the presence of viral genome in the myocardium. The degree of immune activity (anticardiolipin antibody titers) in the V+ patients was as high as that in V- ones. At baseline, the V+ patients had a significantly higher LV EDS and a lower EF than the V- patients. Overall, IST only could lead to a significant increase in EF (from 26.5±0.9 to 36.0±10.8%; p<0.001) and reductions in NYHA functional class from III to II (p<0.001), LV EDS (from 6.7±0.7 to 6.4±0.8 cm; p<0.01), pulmonary artery systolic pressure (from 48.9±15.5 to 39.4±11.5 mm Hg (p<0.01); the IST group had significantly lower mortality rates than the non-IST group (23.9 and 64.3%; p<0.01). At the same time, a significant trend was seen in both V- and V+ patients. The mortality rate in the V+ patients, as a whole, was higher (46.9 and 17.9%; p<0.05). IST leads to a significant improvement of functional indices and it is associated with lower mortality rates in both myocardial V- and V+ patients with LM. A more than 10% EF increase in the first 2 months is associated with a good prognosis. The presence of viral genome in the myocardium (primarily herpesviruses rather than parvovirus-19) is accompanied by more severe initial dysfunction, a less pronounced effect of IST, and higher mortality rates. However, the positive effect of IST also persists in V+ patients. No positive changes (a decrease in EF was observed) were absent only in IST-naïve V+ patients.

An Unexpectedly High Rate of Thrombophilia Disorders in Patients with Superficial Vein Thrombosis of the Lower Extremities

Superficial vein thrombosis (SVT) is a common venous condition. Recent studies have shown that SVT is associated with high frequency of thromboembolic complications: from 22-37% for deep venous thrombosis and up to 33% for pulmonary embolism. Our goal was to assess the prevalence of major hereditary and acquired thrombophilic factors in patients with SVT. Sixty-six patients presenting with primary SVT underwent evaluation for thrombophilia: molecular testing for the factor V Leiden and factor II G20210 A (prothrombin) mutations, protein C, protein S, antithrombin deficiency, presence of lupus anticoagulant, as well as anticardiolipin antibody titers. Patients aged less than 18 years, with confirmed deep vein thrombosis, and pregnant women were excluded. 95.5% were Caucasian, and 62.1% were female gender. Age ranged from 21-88years. Molecular testing showed that 34.2% of patients were heterozygous for factor V Leiden, 23.6% were heterozygous for the factor II mutation, 7.8% had antithrombin deficiency, 2.6% had protein S deficiency, and 2.1% had protein C deficiency. Our study showed that hereditary and acquired thrombophilias are higher than previously expected and reported.

Juvenile lupus: Different clinical and serological presentations compared to adult lupus in Egypt

Aim of the work: We aimed to evaluate the differences in clinical presentation, serological pattern and disease activity between juvenile and adult-onset of Egyptian systemic lupus erythematosus (SLE) patients. Patients and methods: 160 Egyptian SLE patients (80 Adult-onset and 80 juveniles) were included. Patients records were reviewed for clinical and laboratory evaluation on presentation. Disease activity at onset was assessed using SLE Disease Activity Index (SLEDAI). Results: The mean age of the adult patients was 29.9±7.2years and of the juvenile cases (12.8±2.1years). The female:male ratio of the adults was 10:1 while it was 39:1 in the SLE children. The most common clinical presentation among adult SLE was malar rash (75%) followed by articular manifestations (62.5%), while in juveniles, nephritis (78.8%) followed by articular manifestations (71.2%) were the most common. Juvenile patients had more frequent neuropsychiatric (p=0.015) and hematologic abnormalities (p<0.001) at onset; and lupus nephritis (72.5%) compared to adults (36.2%) (p<0.001) during the first year of presentation. Juvenile SLE showed higher frequency of proteinuria (p<0.001), hematuria (p=0.02) and active urinary sediments (p=0.016). Proliferative nephritis was the most common form among both juveniles and adults. Positivity and titres of both anticardiolipin antibodies and lupus anticoagulant were significantly higher in juvenile SLE. Juvenile SLE patients had significantly higher SLEDAI [median (IQR): 12 (10–22)] compared to adults [median (IQR): 8 (4–12)], p<0.001. Conclusion: Juvenile SLE patients differ from adult SLE with more frequent major organs affection and significantly higher serological activity. Earlier and more careful assessment with strict management plan and follow-up are needed in juvenile SLE patients.

Pregnancy failure in patients with obstetric antiphospholipid syndrome with conventional treatment: the influence of a triple positive antibody profile.

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20-30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4-16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2-16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2-10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2-13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment.

Association of Lupus Anticoagulant With Long-Term Damage Accrual in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antiphospholipid antibodies (aPL) are frequently present in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients; however, the prognostic impact of aPL in such patients has not been elucidated. The objective of this study was to determine whether persistent aPL positivity in AAV patients was associated with increased long-term damage accrual. Clinical data were retrospectively collected on all AAV patients who attended the vasculitis clinic at our center over a 4-year period. Data collection included presence of lupus anticoagulant (LAC) and IgG and IgM anticardiolipin (aCL) antibody titers, along with concurrent diagnosis of antiphospholipid syndrome (APS). Accumulation of long-term damage was quantified using the Vasculitis Damage Index (VDI). Data from 116 AAV patients were analyzed. A total of 34% (n = 40) had persistently positive aCL or LAC or a concurrent diagnosis of APS and were classified as AAV/aPL. A total of 76 patients (66%) were classified as AAV alone. LAC was present in a statistically higher proportion of AAV/aPL patients than those in the AAV-alone group (P < 0.0001). Mean VDI score was significantly higher in the AAV/aPL group at mean ± SD 3.54 ± 1.36 as compared to 1.96 ± 1.42 in the AAV-alone group (P < 0.0001). Major vascular damage scores were significantly higher in the AAV/aPL group, with mean ± SD 0.32 ± 0.59 as compared to 0.07 ± 0.26 in the AAV-alone group (P < 0.007). Persistently positive occurrence of aPL, in particular LAC, is present in a significant proportion of AAV patients and is associated with a higher VDI score. Clinicians should consider screening AAV patients for aPL.

Modulation of an aqueous extract of Chinese medicine prescription Anzi Heji () on ratio of CD4+CD25+FOXP3+ regulatory T cells in anticardiolipin antibody-positive patients with threatened abortion.

To evaluate Chinese medicine prescription, Anzi Heji (, AZHJ), on immune regulation of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in anticardiolipin antibody (ACA)-positive patients with threatened abortion. Twenty-seven ACA-positive female patients with threatened abortion in the study group were treated with an aqueous extract of AZHJ 125 mL, twice daily for 4 consecutive weeks. The results were compared with control group composed by 15 healthy pregnant women. The ratio of CD4+CD25+FOXP3+ Treg in peripheral blood was identified by flow cytometry. The indicators of ACA were detected by enzyme-linked immunosorbent assay, and embryo development was checked by B-ultrasound. Compared with the control group, the ratio of CD4+CD25+FOXP3+ Treg cells in the study group was significantly lower before AZHJ treatment (P<0.01) and significantly increased after AZHJ treatment (P<0.01). After treatment, 20 of 27 patients (85%) showed that ACA indicators turned into negative, and 7 cases of quantitative indicators of ACA titers were significantly decreased (P<0.01). Total efficiency of treating miscarriage by AZHJ was 92.59%. AZHJ can regulate the immune function of pregnant women by increasing number of CD4+CD25+FOXP3+ Tregs.