Cardiolipin IgM Research Articles

A rare case of chronic headache

Abstract Cerebral venous thrombosis (CVT) is a relatively uncommon and rare condition worldwide, affecting approximately 1 in 100,000 individuals annually and comprising about 0.5% of all strokes. It is more prevalent in women of childbearing age due to hypercoagulable states. We present a case report of a 19 years old female exhibiting symptoms, including headache, occasionally associated vomiting, blurring of vision and one generalised seizure. On general examination and neurological, there were no significant abnormality found, Fundoscopy revealed blurred disc margins and the presence of papilledema. An emergency non-contrast computed tomography (NCCT) scan of the brain showed normal findings. Subsequently, a magnetic resonance imaging (MRI) scan of the brain indicated partial loss of flow void in the posterior part of the superior sagittal sinus and straight sinus, along with the formation of collateral channels, suggestive of possible subacute dural sinus thrombosis. Additionally, a contrast-enhanced MRI (CEMRI) scan with MR venogram showed filling defects in the posterior part of the superior sagittal sinus and straight sinus, with non-visualization of the left transverse sinus, indicative of subacute to chronic dural venous thrombosis, Beta 2 glycoprotein IgM and Cardiolipin IgM were positive and titres were high. This case with history of headache for 4 years underscores the need for early diagnosis, which could have alleviated suffering and further prevent grave consequences, with an insight to such problems and accessibility to high end imaging diagnosis tools for early recognition and management.

Clinical Characteristics and Anticoagulation Use in Antiphospholipid Syndrome: A Single-Center Retrospective Analysis

Background: Warfarin remains the anticoagulant of choice for patients with antiphospholipid syndrome (APLS). However, conflicting data exists regarding the role of direct oral anticoagulants (DOACs) as reasonable alternatives to warfarin, which has a less desirable side effect profile. In clinical practice, some patients start taking DOACs or aspirin before an official APLS diagnosis is confirmed and these patients may choose to continue a DOAC after an informed discussion with their hematologist. To gain a better understanding of anticoagulant use in APLS at our center, we conducted a retrospective study to assess the clinical characteristics of patients diagnosed with APLS. Methods: All patients with an ICD-10 code indicating APLS from January of 2020 to April of 2023 were included. Patient characteristics, relevant laboratory testing (lupus anticoagulant, beta-2 glycoprotein IgG/IgM, and anti-cardiolipin IgG/IgM), and treatment history were extracted from the electronic medical record. Patients were deemed to have single positivity if any one of the following were present: detectable lupus anticoagulant, elevated (defined as >40 GPL) beta-2 glycoprotein (B2GP) IgG or IgM, or elevated cardiolipin IgG or IgM both on initial and confirmatory testing (performed approximately 12 weeks later). Similarly, double positivity was defined as the presence of two of these biomarkers and triple positive was defined as the presence of three of these biomarkers. Initial laboratory testing results are included in Table 1. Statistical analysis was conducted using the SAS software (SAS Enterprise Guide 7.1) and the R Core Team (R 4.2.2). Continuous variables such as BMI and age were evaluated using the Wilcoxon rank-sum test, while categorical variables were assessed using Fisher's Exact Test and Chi-squared test. Results: Seventy-two patients were included in our analysis. Mean age and BMI were 56.3 ± 16.8 years and 32.3 ± 11.2, respectively. The majority of patients were female (69.4%) and white (83.8%). Approximately half of all patients had single positivity (64.4%) and more than half had detectable lupus anticoagulant (58.7%). Cardiolipin IgM was the most frequently (36.1%) elevated biomarker. Patient characteristics between the DOAC/aspirin and warfarin/enoxaparin cohorts were not significantly different; however, significantly more patients with single positivity received DOAC/Aspirin rather than warfarin/enoxaparin (77.8% vs.43.5%, p = 0.012). There was no statistically significant difference between the frequency of arterial complications in patients who took DOAC/Aspirin (4 events in 39 patients) versus those who took warfarin/enoxaparin (1 event in 33 patients), p = 0.366. The majority of arterial complications (4 of 5 events) occurred in patients with double and triple positivity. In addition, a logistical regression was performed regarding different characteristic effects on positivity level (single, double or triple laboratory positive), which found the presence of lupus anticoagulant had a significant association with higher likelihood of double/triple positivity (p = 0.048). Conclusion: This study provides potential reassurance for clinicians regarding the use of DOACs during the investigative phase of APLS and supports the continuation of DOAC therapy in patients, particularly those with single positivity, after careful evaluation and shared decision-making with patients. However, caution should be kept when considering DOAC use in patients with lupus anticoagulant, double, or triple positivity, due to concerning arterial events. Further large multi-center randomized clinical trials are necessary in the future to clarify the role of DOACs in APLS.

P21 Lupus or else?

P21 Lupus or else?

Autoimmune disease with libman sacks endocarditis presenting with acute limb ischemia

Background: Libman Sacks Endocarditis is rare, nonbacterial vegetation of the heart valves. Most commonly seen in association with solid cancers and autoimmune diseases. Case: A 64-year-old male came in with sudden onset left upper arm numbness, pain and pallor which worsened with movement. On examination, he had feeble pulses of the left upper extremity and an aortic diastolic murmur of the heart. He underwent an angiogram which revealed decreased flow distal to the brachial artery and therefore was scheduled for an emergent embolectomy. An echocardiogram showed a mass on the aortic valve. Repetitive blood cultures were negative. Autoimmune workup showed positive lupus anticoagulant and cardiolipin IgM, possibly suggesting antiphospholipid syndrome. Unfortunately, we were unable to follow up on the thrombophilia workup at 12 weeks. Conclusion: Autoimmune disease has a strong association with Libman Sacks endocarditis, treatment with warfarin is preferred and valve replacement is necessary in some cases.

Inflammation and thrombo-occlusive vessel signalling in benign atrophic papulosis (Köhlmeier-Degos disease).

Although the merely cutaneous, benign form of the extremely rare disease atrophic papulosis (Köhlmeier-Degos disease) may occasionally develop into the systemic, malignant form with time, it is unclear whether it exhibits any systemic characteristics. To determine whether benign atrophic papulosis exhibits inflammatory and thrombo-occlusive signals and to classify it according to the Chapel-Hill classification of vasculitis. In a monocentric, controlled study, levels of cytokines (IL-1β, IL-6, IL-8, IFNγ, MCP-1, VEGF, TNFα, TGF-β1), antiphospholipid antibodies (cardiolipin IgG/A/M, cardiolipin IgG, cardiolipin IgM, β2-glycoprotein IgG/A/M, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, phosphatidyl ethanolamine and sphingomyelin A), antibodies against proteinase-3 IgG and myeloperoxidase IgG, antinuclear antibodies and extractable nuclear antigen were assessed in blood samples of six benign atrophic papulosis patients and six age- and sex-matched healthy controls. IL-8 was only detectable in patients' serum. VEGF was reduced and cardiolipin IgG/A/M and β2-glycoprotein antibodies were increased in the patients' group. ANA were only detected in three patients, and ENA were negative throughout. No differences were detected between the other investigated markers. This is the first study evaluating systemic inflammatory and thrombo-occlusive vessel signalling in benign atrophic papulosis and provides evidence of a non-antineutrophil cytoplasmatic antibodies immune-complex small vessel vasculitis according to the Chapel-Hill classification. These findings corroborate its systemic character despite the apparent missing involvement of systemic organs.

How useful current workup panel of young stroke? - Audit data from UAE

Current stroke workup for young patients in Al Ain hospital (AAH) consist of cardiac, radiologic evaluation, and multiple blood tests. Our objective was to assess the efficiency of the blood panel tests. Retrospective data from AAH Stroke registry was reviewed for the year 2018. We included patient of 50 years old and younger who had ischemic stroke (IS) and transient ischemic attack (TIA). Gender, Nationality, Stroke subtype, and Panel of blood tests were evaluated. Based on the Integrated Ischemic Stroke Guidelines of AAH; 22 blood tests used for screening of uncommon causes. Based on their results, they were classified as significant (≧10%) moderately significant (<10%) and insignificant (0%). 66 patients met inclusion criteria. 7 patients had TIA and 59 IS. 51 males and 15 females, composed of 65% Asian, 18% Emirati, and 17% Arab. Of the 22 tests; 6 showed to be significant, including; TFT, ESR, factor V Leiden, activated protein C resistance, lupus anticoagulant and urine microalbumin level. 9 were moderately significant, including; homocysteine, syphilis screen, antithrombin III assay, Protein S Free Ag, ANA, C3 complement, C4 complement, Cardiolipin IgG and Beta-2-microglobulin. 6 tests showed no abnormality, including; Vitamin D level, Cardiolipin IgM, ANCA-Panel, Anti-Ds DNA, fibrinogen level, protein C and Brucella titer. We recommend that tests which showed no abnormality could be removed from our panel and tests which showed moderately significant abnormality can be done if clinically indicated. Further prospective studies based on these results can yield in updating the current guidelines.

УРАЖЕННЯ ЩИТОПОДІБНОЇ ЗАЛОЗИ У ХВОРИХ НА ХРОНІЧНИЙ ГЕПАТИТ С ТА ЇХ ВЗАЄМОЗВ’ЯЗОК ЗІ ЗМІНАМИ ОРГАНОНЕСПЕЦИФІЧНИХ АВТОАНТИТІЛ

Хронічний гепатит С, на відміну від гепатитів іншої етіології, характеризується високою частотою розвитку позапечінкових проявів. Роль імунних порушень в розвитку HCV-асоційованих уражень щитоподібної залози на сьогодні вивчається. Мета роботи – визначити особливості ураження щитоподібної залози у хворих на хронічний гепатит С та дослідити їх взаємозв’язок зі змінами органонеспецифічних автоантитіл.Пацієнти і методи. В дослідження було включено 225 хворих на хронічний гепатит С. Для діагностики ураження щитоподібної залози досліджували вміст у сироватці крові тиреотропного гормону, вільного трийодтироніну, вільного тироксину, антитіл до тиреоїдної пероксидази, антитіл до тиреоглобуліну. Спеціальні методи дослідження включали визначення вмісту в сироватці крові: антинуклеарних антитіл, ревматоїдного фактора, кардіоліпіну IgM та IgG, циркулюючих імунних комплексів. Результати. У 19,6 % хворих на хронічний гепатит С розвивається ураження щитоподібної залози, що проявляється змінами у крові вмісту тиреотропного гормону, вільних тироксину і трийодтироніну, появою лише органоспецифічних автоантитіл або поєднанням зазначених змін. Переважає розвиток гіпотиреозу (68,2 %). Ураження щитоподібної залози розвивається частіше у жінок, ніж у чоловіків (32,1 проти 8,4 %, р&lt;0,01). У хворих на хронічний гепатит С з ураженням щитоподібної залози, на відміну від пацієнтів без цього прояву, частіше виявляються кардіоліпін IgM й IgG, антинуклеарні антитіла, вищий вміст кардіоліпіну IgM й IgG, а рівень підвищення антитіл до тиреоїдної пероксидази корелює (р&lt;0,01) з вмістом ревматоїдного фактора IgM (r=+0,66) та кардіоліпіну IgM (r=+0,39). Наявний прямий кореляційний зв’язок між кількісним вмістом антитіл до тиреоїдної пероксидази та вмістом ревматоїдного фактора RF-IgM (r=+0,66; р&lt;0,01) й вмістом кардіоліпіну IgM (r=+0,39; р&lt;0,05) підтверджує роль автоімунних порушень в формуванні HCV-асоційованих уражень щитоподібної залози. Висновки. У кожного п’ятого хворого на хронічний гепатит С розвивається ураження щитоподібної залози, що найчастіше характеризується як гіпотиреоз. За наявності ураження щитоподібної залози у хворих на хронічний гепатит С частіше виявляються кардіоліпін IgM й IgG, антинуклеарні антитіла. Рівень підвищення антитіл до тиреоїдної пероксидази корелює з вмістом ревматоїдного фактора IgM та кардіоліпіну IgM.

CLINICAL, LABORATORY AND IMMUNOLOGICAL FEATURES IN PATIENTS OF SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: To describe the clinical, laboratory and immunological features in patients with systemic lupus erythematosus (SLE). Methods: This was a descriptive cross-sectional study of 120 SLE patients admitted to Rheumatology department of Cho Ray Hospital and 60 healthy subjects on routine exams from November 2013 to July 2015. Results: Of the 120 patients, 114 were females (95.0%) and 6 were males (5.0%), giving a female to male ratio of 19:1. The patients’ age varied from 16 to 64 years old, mean 27.86. The systematic symptoms include: hypertension (4.2%), oedema (35.8%), fatique (78.3%) and fever (66.7%). The clinical criteria include: photosensitivity (80%), malar rash (69,2%), discoid rash (2,5%), nasal DLE (9.2%), oral DLE (30.0%), alopecia (55.8%), arthritis (45.8%), serositis: cardiac effusion (5.8%), pleural effusion (9.2%), renal: proteinuria per day (39.2%), hematuria (53.3%), neurologic: psychosis (3.3%), headache (7.5%), anemia (66.7%), leukopenia (22.5%), lymphopenia (28.3%), thrombocytopenia (10.0%). The immunological criteria include: positive ANA (97.5%), positive anti-dsDNA (90.0%), positive anti Sm (36.7%), positive anti cardiolipin IgG (18.3%), positive anti cardiolipin IgM (6.7%), positive direct Coomb test (20.0%). Hypocomplementemia of C3: sensitivity (95.0%), specificity (88.3%). Hypocomplementemia of C4: sensitivity (81.7%), specificity (96.7%).Conclusions: C3, C4 in serum are good tests for diagnosing Systemic Lupus Erythematosus according to SLICC 2012, hypocomplementemia of C3 and C4 have high sensitivity and specificity. Keywords:SystemicLupusErythematosus,C3,C4.

Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

Correlation between beta 2-glycoprotein antibodies and antiphospholipid antibodies in patients with reproductive failure.

Antiphospholipid antibodies (APAs) are important in the etiology of reproductive failure. Studies have shown that binding proteins are necessary for the detection of APAs. One of these, beta 2-glycoprotein, has been shown to be necessary for detection of anticardiolipin antibodies. It is felt that some APAs may be directed to the binding protein itself, or to a combination of the binding protein and phospholipid. In this study, a comparison of APAs vs. anti beta 2-glycoprotein antibodies was performed on the sera of 123 women younger than 40 years of age with a history of reproductive failure. Antibodies to six phospholipid epitopes, cardiolipin, phosphatidyle-thanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol, and phosphatidylserine, were measured. Of the 123 women tested, 33 had one or more positive immunoglobulin (Ig)G antibodies to phospholipids, of which 9 were to cardiolipin. However, only 1 of 123 women had IgG antibodies to beta 2-glycoprotein and she was APA negative. Thirty-eight of 123 women had one or more IgM antibodies to phospholipids, with none directed to cardiolipin IgM. In contrast, only 8 of the 123 women had IgM antibodies to beta 2-glycoprotein. Five of the eight patients had IgM APA; 4 of 5 had IgM antibodies to PE, 1 to PI. There is no correlation between beta 2-glycoprotein antibodies and APA status in this population. To date, our most sensitive test for detecting phospholipid autoimmune-mediated in vitro fertilization failure still appears to be the ELISA assay for APA.