AB0318 RISK FOR CONCOMITANT AUTOIMMUNITY IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME; A SWEDISH COHORT STUDY

BackgroundIn patients with the antiphospholipid syndrome (APS), recurrent thrombosis (re-thrombosis) is common despite anticoagulation and the mortality rate is high. Concomitant systemic autoimmune rheumatic diseases (SARD) are frequent in patients...

PurposeAnti-phospholipid antibodies (aPL) analyzed by line immunoassay (LIA) can recognize beta2-glycoprotein I (β2GPI) domain 1 (D1) epitopes depending on β2GPI binding to distinct phospholipids. The aPL LIA was compared with consensus ELISA to investigate whether both techniques can discriminate anti-phospholipid syndrome (APS) patients from aPL-positive, systemic autoimmune rheumatic diseases (SARD) patients without clinical symptoms of APS and controls.MethodsThirty-four APS patients (14 arterial/venous thrombosis, 16 pregnancy morbidity, and 4 both), 41 patients with SARD lacking clinical APS criteria but demonstrating positivity for anti-β2GPI (aβ2GPI) IgG, and 20 healthy subjects (HS) were tested for aPL to cardiolipin (aCL), phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol (aPG), phosphatidylinositol, phosphatidylserine, β2GPI, prothrombin, and annexin V by LIA. Samples were also tested for aCL, aβ2GPI, aβ2GPI-domain 1 (aD1), and aβ2GPI-domains 4–5 (aD4–5) by ELISA and for lupus anti-coagulant.ResultsComparison of LIA with ELISA revealed a good agreement for the consensus criteria aPL aβ2GPI and aCL IgG (kappa = 0.69, 0.68, respectively) and a moderate agreement for IgM (kappa = 0.52, 0.49, respectively). Regarding ELISA, aD1/aD4–5 demonstrated the best performance of differentiating APS from asymptomatic SARD [area under the curve (AUC): 0.76]. aPG IgG had the best performance by LIA (AUC: 0.72) not significantly different from aD1/aD4–5. There was a good agreement for aPG IgG with aD1/aD4–5 (kappa = 0.71).ConclusionsaD1/aD4–5 (ELISA) and aPG IgG (LIA) differentiate APS from SARD patients. PG appears to interact with β2GPI of APS patients and exposes D1 thereof for disease-specific aPL binding in LIA.

Thrombotic Risk Factors, Antithrombotic Therapy, and Outcomes of Asymptomatic Carriers of Antiphospholipid Antibodies and Patients with Antiphospholipid Syndrome

Patients with primary or secondary antiphospholipid syndrome (APS) have an increased risk of recurrent venous, arterial thrombosis and pregnancy complications. Therefore, determining thrombotic risk is important when individualizing antithrombotic therapy in patients with APS. To identify thrombotic risk factors in a cohort of APS patients. We conducted a retrospective review of APS patients who received care at a Hematology clinic of a university medical center from 2004 to 2017. Demographics, clinical features, antithrombotic therapy and thrombotic outcomes were collected. Time to event analysis identified clinical risk factors for thrombosis. The time varying effects of antithrombotic treatments on thrombosis outcome were analyzed. We identified 84 subjects with APS with a median age at diagnosis of 40.7years [interquartile range [IQR] 33.5-57.6]. The majority were female (n = 63, 75%) and White (n = 45, 54%). Twenty-eight (33%) patients had concomitant autoimmune disease (AID) and of these, 15 (54%) had systemic lupus erythematosus. A thrombotic event occurred in 15 (18%) patients during a median follow-up of 48months. A significantly higher rate of thrombotic events was observed in APS patients with AID compared to those without AID (hazard ratio (HR) 4.93, 95% CI 1.7-14.3, p = 0.04), and in black patients compared to whites (HR 5.94, 95% CI 1.1-32.1, p = 0.039). Patients on therapeutic anticoagulation regardless of type (warfarin, low molecular weight heparin or direct oral anticoagulants) were significantly less likely to have a recurrent thrombotic event compared to those on prophylactic anticoagulation (HR 0.11, 95% confidence interval [CI] 0.031-0.395, p = 0.001). However the numbers are too small to draw conclusions. Our study suggests that APS patients with concomitant AID and of Black race are at increased risk of recurrent thrombotic events.

Although the association between multiple sclerosis and trigeminal neuralgia (TN) is well established, little is known about TN pain characteristics and postoperative pain outcomes after microvascular decompression (MVD) in patients with TN and other autoimmune diseases. In this study, we aim to describe presenting characteristics and postoperative outcomes in patients with concomitant TN and autoimmune disease who underwent an MVD. A retrospective review of all patients who underwent an MVD at our institution between 2007 and 2020 was conducted. The presence and type of autoimmune disease were recorded for each patient. Patient demographics, comorbidities, clinical characteristics, postoperative Barrow Neurological Institute (BNI) pain and numbness scores, and recurrence data were compared between groups. Of the 885 patients with TN identified, 32 (3.6%) were found to have concomitant autoimmune disease. Type 2 TN was more common in the autoimmune cohort ( P = .01). On multivariate analysis, concomitant autoimmune disease, younger age, and female sex were found to be significantly associated with higher postoperative BNI score ( P = .04, <0.001, and <0.001, respectively). In addition, patients with autoimmune disease were more likely to experience significant pain recurrence ( P = .009) and had shorter time to recurrence on Kaplan-Meier analysis ( P = .047), although this relationship was attenuated on multivariate Cox proportional hazards regression. Patients with concomitant TN and autoimmune disease were more likely to have Type 2 TN, had worse postoperative BNI pain scores at the final follow-up after MVD, and were more likely to experience recurrent pain than patients with TN alone. These findings may influence postoperative pain management decisions for these patients and support a possible role for neuroinflammation in TN pain.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Effects of Autoimmune Disease on Non-High Risk MDS Outcomes: A Population Analysis

Poor Agreement between Commercially Available Anti-Cardiolipin and Anti-β2glycoprotein I IgG and IgM Solid Phase Assays Hampers Uniformity in the Classification of Antiphospholipid Syndrome Patients

Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH

<h3>Background</h3> Antiphospholipid syndrome (APS) is a heterogeneous disease, with different phenotypes which may widely vary from classical thrombotic or obstetrical manifestations to catastrophic antiphospholipid syndrome (CAPS). APS can be associated...

Background:Antiphospholipid syndrome (APS) is an acquired thrombophilia caused by antiphospholipid autoantibodies (aPL). Diagnosis of APS is based on laboratory and clinical criteria (thrombosis or pregnancy‐related complications). The detection of lupus anticoagulant (LA), IgG and/or IgM isotype anti‐cardiolipin (ACA) and anti‐β2 glycoprotein I antibodies (aβ2GPI) constitutes the laboratory tests of APS. The β2GPI protein consists of 5 domains and an association of thrombosis with the presence of antibodies directed against domain 1 (aD1β2GPI) was suggested in the literature.Aims:The aim of this study was to investigate the presence of IgG isotype aD1β2GPI and its association with thrombosis in our patient cohort.Methods:Using a chemiluminescence immunoassay (INOVA QUANTA Flash β2GPI‐Domain I, ACL Acustar) we have measured aD1β2GPI titer in 51 patients having IgG isotype aβ2GPI (APS with thrombosis: n = 21; APS with pregnancy loss: n = 7; other autoimmune disease: n = 18; aPL positive asymptomatic patients, n = 5).Results:In patient samples the concordance between the presence of IgG isotype aD1β2GPI and aβ2GPI was 67% and the correlation between these antibody titers was high (r = 0.71). We have found that the level of IgG isotype anti‐β2GPI was significantly higher in thrombotic APS patients compared to all other patient groups. The aD1β2GPI titer was the highest in thrombotic patients however, there was no significant difference in the antibody titer among the patient groups. The IgG isotype aβ2GPI and aD1β2GPI titers were significantly higher in triple positive patients (LA, ACA and aβ2GPI positive) than in double positive patients (ACA and aβ2GPI positive). In the aD1β2GPI positive group 47% of patients had thrombosis, while in the aD1β2GPI negative group this figure was only 29%, however, the association of aD1β2GPI positivity with thrombosis was non‐significant.Summary/Conclusion:This study provides further evidence that the large majority of IgG isotype aβ2GPI is directed against domain 1. Since the concordance between the two antibody positivity was not 100% and aD1β2GPI negative patients can present with thrombosis, we conclude that monitoring aD1β2GPI cannot replace detection of aβ2GPI in the laboratory diagnosis of APS.

Clinical and prognostic significance of antinuclear antibodies in primary antiphospholipid syndrome: A multicenter retrospective study.

Role of anti‐domain 1‐β2glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome

It has been suggested that only antibodies against domain 1 (D1) of β2 -glycoprotein I (β2 GPI) are pathogenic and diagnostic. The role of antibodies against other β2 GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti-β2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in control groups of patients with systemic autoimmune rheumatic diseases and in asymptomatic antiphospholipid antibody (aPL) carriers. We evaluated 159 subjects with persistently positive, medium or high-titer anti-β2 GPI IgG, including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31 women with obstetric primary APS, 42 aPL-positive patients with systemic autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred healthy donors were included. Anti-β2 GPI D1 and D4/5 IgG were tested on research enzyme-linked immunosorbent assays containing recombinant β2 GPI domains. As compared to other groups, aPL carriers displayed higher frequency/titer of anti-D4/5 IgG. Unlike anti-D4/5, anti-D1 IgG antibodies were more frequent and at higher titer in triple than in single or double aPL-positive subjects. An anti-D1 to anti-D4/5 ratio of ≥1.5 was predictive of systemic autoimmunity (odds ratio 3.25 [95% confidence interval 1.45-7.49], P = 0.005). Neither anti-D1 nor anti-D4/5 antibodies were associated with APS clinical criteria. Anti-D1 IgG is the preferential specificity not only in vascular and obstetric primary APS, but also in patients with systemic autoimmune rheumatic disease with no clinical features of APS. Conversely, aPL carriers do not have a polarized profile toward D1. Combined testing for anti-β2 GPI IgG with different domain specificity allows a more accurate aPL profiling, with polarization toward anti-D1 IgG as a possible fingerprint of systemic autoimmunity.

BackgroundThe antiphospholipid syndrome (APS) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (APL). Antinuclear antibodies (ANA) can be detected in...