Influence of anticardiolipin and anti-β2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification

Background: Anticardiolipin (aCL) and anti-beta 2 glycoprotein I (a beta 2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.Methods: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and a beta 2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods.Results: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated.Conclusions: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.Background: Anticardiolipin (aCL) and anti-beta 2 glycoprotein I (a beta 2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.Methods: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and a beta 2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods.Results: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated.Conclusions: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.A

Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis

Extensive Pulmonary Embolism in late pregnancy associated with Anticardiolipin Antibodies

The leading cause of morbidity and mortality during pregnancy and the puerperium is venous thromboembolism. Though uncommon, the risk is five times higher in a pregnant woman than in a non-pregnant woman of similar age.1,2 In pregnancy, all three underlying factors for venous thrombosis are present: hypercoagulability, venous stasis and vascular damage (Virchow's triad). Of these, the most constant predisposing factor is increasing venous stasis due to the pressure of the gravid uterus on the pelvic vasculature. In addition the presence of a thrombophilia, (congenital or acquired) will increase this risk substantially. During pregnancy hypercoagulability is a physiological preparation for the haemostatic challenge of delivery. There are increases in procoagulant factors, such as von Willebrand factor, factor VIII, factor V, and fibrinogen together with an acquired resistance to activated protein C and a reduction in protein S. Increases in plasminogen activator inhibitors impair fibrinolysis. The third factor of this triad, vascular damage, is a possible complication of trophoblastic invasion of the uterine spiral arterioles or of delivery.peer-reviewe

Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis

It is unusual for acute disseminated encephalomyelitis and multiple sclerosis to present as purely psychiatric disorders. We report five patients with such demyelinating diseases and symptoms of psychosis, depression or anxiety. The importance of excluding demyelination as the basis for these psychiatric disturbances is emphasized, especially in the presence of unexplained neurologic findings. The possible relationship between psychiatric symptoms and demyelinating disorders is explored

Determination and Correlation of Anticardiolipin Antibody with High Sensitivity C- reactive Proteins and its Role in Predicting Short Term Outcome in Patients with Acute Coronary Syndrome

Anticardiolipin antibody (aCL) is considered to be an independent risk factor while high sensitivity C reactive protein (hsCRP) is an established marker for coronary artery disease. This study was conducted to determine levels of aCL antibodies and hsCRP, their correlation and role in predicting recurrence of events in patients presenting with Acute Coronary Syndrome (ACS). Sixty patients admitted with Acute Coronary Syndrome were followed up for 7 days or until discharge. Patients were classified into two groups as those having experienced an ischemic event needing intervention within 7 days (Group I) and other having an event free recovery (Group II). aCL antibody and hsCRP levels were estimated and compared in these two groups. Twenty age and sex matched disease free persons served as controls. The levels of aCL were significantly higher in patients with ACS as compared to the controls (p=0.020). However the levels of aCL in Group I (13.39±9.46 GPL-U/ml) and Group II (13.51±9.93 GPL-U/ml) were not significantly different (p =0.838). The mean hsCRP levels were higher in cases with an event (23.30±10.68 mg/dl) than in cases without an event (20.60±11.45mg/dl) though it was not significant statistically (p=0.389). aCL and CRP were not found to be significantly correlated in causing the recurrence of events(p=0.178). Therefore anticardiolipin antibody is an independent risk factor which could be implicated in the pathogenesis of ACS. However it is not significantly associated with recurrence of short-term events in patients with ACS. Also, aCL antibody does not have significant correlation with hSCRP in causing recurrence of events in the patients of acute coronary syndrome

Patients with Essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis

A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 200 elderly controls (> 50 years) there was a significant increase in anticardiolipin IgM (p < 0.0001) and anti β2 glycoprotein I (anti-β2GPI) IgM (p < 0.0001) antibodies in ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04, relative risk 2.0 (95% confidence intervals 1.03-3.86); these patients did not differ in terms of other clinical features. The prevalence of thrombosis in patients with dual APA (6/7) was significant when compared to those with single APA (p = 0.02) and the remaining patients (p < 0.0002). Also anti-β2GPI IgM antibodies either alone, or in combination with another APA, were associated with thrombosis (p = 0.02). These results suggest that the prevalence of APA in ET and their influence upon thrombotic risk merit investigation in a larger study

Implications of Antiphospholipid and Antineutrophilic Cytoplasmic Antibodies in the Context of Postinfectious Glomerulonephritis.

While antineutrophil cytoplasmic antibody (ANCA) positivity has been documented in some patients with postinfectious glomerulonephritis (PIGN) and is associated with more severe disease, antiphospholipid antibodies (APA) are not known to be a common occurrence. We describe a child with severe acute kidney injury who was noted to have prolonged positivity of both ANCA and APA; a renal biopsy showed noncrescentic immune complex mediated glomerulonephritis with subepithelial deposits compatible with PIGN. He recovered without maintenance immunosuppressive therapy and at last follow-up had normal renal function. We discuss the cooccurrence and implications of ANCA and APA in children with PIGN

Do we need broad immunological work-up in all patients with CIS?

BACKGROUND: The aim of this study was to determine the prevalence of altered immunological tests and their clinical significance in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). ----- PATIENTS AND METHODS: The information was gathered from medical records of patients hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010 period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50, anti-TPO, AST and RF antibodies tested. ----- RESULTS: From 726 patients with CIS that were reviewed, the complete battery of immunological tests was performed in 418 of them (57.6%), representing our cohort. Altered tests were found in 235 patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM, and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs aCL IgM, p=0.155). None of the patients had any clinical manifestations other than MS symptoms. ----- CONCLUSION: These results indicate that significant number of patients with CIS have altered immunological tests but nevertheless none of them had clinical expression of any other autoimmune disease making them clinically insignificant. In conclusion there is no need to perform extensive immunological work-up in all patients with CIS. Contrary, our results argue for more focused testing rather than a battery of screening tests