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Francesca Pregnolato,
Cecilia B Chighizola, Susan Encabo,
Zakera Shums,
Gary L Norman,
Armando Tripodi,
Veena Chantarangkul,
Tiziana Bertero,
Valeria De Micheli,
Maria Orietta Borghi,
Pier Luigi Meroni
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ABSTRACT: Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite(®) aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3 %, rising to 87.6 % when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.
Immunologic Research 04/2013; · 3.03 Impact Factor
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ABSTRACT: OBJECTIVE: To investigate the prevalence of primary biliary cirrhosis (PBC) and PBC-associated autoantibodies in Japanese systemic sclerosis (SSc) patients. METHODS: Clinical data from 225 Japanese SSc patients were retrospectively obtained. Serum samples from these patients were examined for PBC-associated autoantibodies, anti-mitochondrial M2 antibodies (AMA), anti-sp100 antibodies (anti-sp100), and anti-gp210 antibodies (anti-gp210) by enzyme-linked immunosorbent assay. RESULTS: Of 225 patients, 37 (16.4%) had AMA, 13 (5.8%) had anti-sp100, and 3 (1.3%) had anti-gp210. Three patients were positive for both AMA and anti-sp100, and 2 were positive for both AMA and anti-gp210. PBC was found in 22 (9.8%) patients positive for AMA with or without anti-sp100 or anti-gp210, but not in those with anti-sp100 or anti-gp210 without AMA. Furthermore, 13 patients lacking these three antibodies were diagnosed with or suspected of PBC by liver biopsy and/or their clinical manifestation. Multivariable analysis revealed that AMA and anti-centromere antibodies were independently associated with PBC in SSc patients, while anti-sp100 and anti-gp210 were not. CONCLUSIONS: This study has demonstrated even higher prevalence of both PBC-associated autoantibodies and PBC in the Japanese SSc population than in the Caucasian SSc population. AMA and anti-centromere antibodies are likely to indicate increasing risk of PBC in SSc patients.
Modern Rheumatology 02/2012; · 1.58 Impact Factor
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Laura Andreoli,
Cecilia Nalli,
Mario Motta,
Gary L Norman,
Zakera Shums, Susan Encabo,
Walter L Binder,
Monica Nuzzo,
Micol Frassi,
Andrea Lojacono,
Tadej Avcin,
Pier-Luigi Meroni,
Angela Tincani
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ABSTRACT: Anti-β₂-glycoprotein-I (anti-β₂GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β₂GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions.
To evaluate the fine specificity of anti-β₂GPI in adults and infants.
Three groups were examined-group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS.
were selected based on positive anti-β₂GPI IgG results. Serum samples were tested for anti-β₂GPI IgG D1 and D4/5 using research ELISAs containing recombinant β₂GPI domain antigens.
Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B.
The specificity for D4/5 suggests that anti-β₂GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the 'innocent' profile of such antibodies.
Annals of the rheumatic diseases 10/2010; 70(2):380-3. · 8.11 Impact Factor
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ABSTRACT: Atrophic body gastritis (ABG) is an autoimmune condition eventually manifesting itself as pernicious anemia (PA). Parietal cell autoantibodies (PCAs) and intrinsic factor autoantibodies (IFAs) are considered characteristics of these conditions. Recent studies on IFA and PCA frequency with respect to cobalamin deficiency in biopsy-proven ABG patients are lacking. We addressed this issue using new enzyme-linked immunosorbent assay (ELISA)-based assays.
Sera from 165 patients with histologically diagnosed ABG and 113 controls were tested for IFA and PCA using ELISA. A total of 81 ABG patients had cobalamin deficiency and macrocytic anemia (Group 1-PA), 36 had cobalamin deficiency without macrocytic anemia (Group 2), and 48 had normal cobalamin levels (Group 3).
IFAs were detected in 44/165 ABG patients (27% sensitivity) and in 0/113 controls (100% specificity). PCAs were detected in 134 ABG patients (81% sensitivity) and in 11 controls (90% specificity). In Group 1, IFAs showed 37% sensitivity and 100% specificity, whereas PCAs showed 81% sensitivity and 90% specificity. Combining IFA and PCA testing increased the sensitivity to 61% in all ABG patients and to 73% in Group 1, while maintaining 100% specificity.
IFAs are 100% specific for biopsy-proven ABG and occurred in 27% of patients. PCAs occurred in 81% of ABG patients and in 10% of controls. Combining IFA and PCA testing significantly increases their diagnostic performance for ABG and PA, yielding a 73% sensitivity for PA. The non-invasive combined PCA and IFA assessment may be useful in selecting patients at risk for autoimmune gastritis to be confirmed by gastroscopic-histologic examination.
The American Journal of Gastroenterology 07/2009; 104(8):2071-9. · 7.28 Impact Factor
