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ABSTRACT: OBJECTIVE: The effect of low-dose aspirin (LDA) on pregnancy outcome in antiphospholipid (aPL)-positive women not fulfilling the criteria for antiphospholipid antibody syndrome (APS) was evaluated retrospectively. METHODS: We evaluated 139 pregnancies of 114 aPL-positive women not fulfilling the Sydney classification criteria for definite APS (104 treated with LDA, 35 untreated). Inclusion criteria consisted of (1) any titer of aPL and no previous pregnancy or no pregnancy losses (defined as aPL carriers); (2) any titer of aPL and 1 or 2 pregnancy losses before the 10th gestational week. No women had previous thrombosis. The rate of pregnancy loss, gestational age at delivery, and birth weight percentile were compared in the treated and untreated patients. Associations between clinical and laboratory characteristics and pregnancy outcomes were investigated. RESULTS: The rate of pregnancy loss was low in both treated and untreated groups (7.7% vs 2.9%, respectively). There were no statistically significant differences in the rate of pregnancy loss, gestational age at birth, or birth weight percentile in the treated and untreated groups. There were significant associations between gestational age at birth ≤ 34th week and positivity for lupus anticoagulant (p = 0.025) and anti-ß(2)-glycoprotein I IgG antibodies at titers > 99th (p = 0.016). CONCLUSION: LDA treatment does not appear to improve pregnancy outcome in low-risk women not fulfilling the criteria for APS. Because antibody profile seems to influence pregnancy outcome, further studies of patients stratified according to their antibody profile are warranted.
The Journal of Rheumatology 02/2013; · 3.69 Impact Factor
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ABSTRACT: Background
Despite the efficacy of angiotensin-converting enzyme (ACE) inhibitors, the prognosis of patients with Scleroderma renal crisis (SRC) is characterized by a high rate of mortality and progression into end-stage renal disease (ESRD). Our aim was to evaluate the prognosis of SRC in our cohort of scleroderma patients.Methods
We reviewed clinical charts of all our patients who developed SRC from 1980 to 2005. Outcome measures were ESRD, patients' survival and SRC-related mortality. ESRD was defined as the need for chronic dialysis; survival was calculated from the time of SRC occurrence by Kaplan-Meier method. All patients were treated with ACE inhibitors and 10 patients were also treated with plasma exchange (PEx). Indications to PEx were concomitant micro-angiopathic haemolytic anaemia or intolerance to high doses of ACE inhibitors. SPSS package was used for calculation.ResultsOf 606 patients, affected with systemic sclerosis, who came at our observation during the aforementioned interval, 20 (3.3%) developed SRC. One year after SRC onset, 55% of patients developed ESRD. The survival rate was 70% at 1 year and 50% at 5 years; the mortality rate related to SRC was 35%. Notably, in the subgroup of patients treated with PEx, 20% developed ESRD; the survival rate was 90% at 1 year and 70% at 5 years; the mortality rate related to SRC was 10%.Conclusions
Short-term prognosis of SRC has improved, but long-term prognosis remains disappointing. PEx in addition to ACE inhibitors seems to be a therapeutic option in patients with SRC who develop micro-angiopathy or are intolerant to high doses of ACE inhibitors.
Nephrology Dialysis Transplantation 08/2012; · 3.40 Impact Factor
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ABSTRACT: Conventional therapy with aspirin and/or heparin is at times incapable of preventing complications in high risk pregnancies of patients with antiphospholipid syndrome (APS). In those cases, a so-called second-line treatment protocol is used in addition to conventional therapy strategies. This manuscript is a report on three APS pregnant patients who were successfully treated with plasma exchange (PE) (two cases) or with immunoadsorption (IA) (one case) as a second-line treatment strategy. The efficacy of these procedures in removing anticardiolipin (aCL) and anti-β(2)glycoprotein I (aβ(2)GPI) antibodies from blood was evaluated. Serum samples were collected before and after 87 apheretic treatment sessions. Serum IgG/M aCL and IgG/M aβ(2)GPI antibodies were determined using an "in-house" enzyme-linked immunosorbent assay and showed that all three patients had medium/high IgG aCL and aβ(2)GPI titers. All three women had a successful pregnancy. A significant decrease in IgG aCL (P = 0.0001) and aβ(2)GPI (P = 0.0001) antibody titers was observed after PE and IA sessions. There was moreover a significant, steady fall in serum IgG aCL pretreatment levels during the course of all three pregnancies (P = 0.0001, P = 0.0001, P = 0.001). The fall in IgG aβ(2)GPI was significant in two of the patients (P = 0.0001, P = 0.0001) both with high antibody titers, but not in one with medium antibody titers, who was treated with PE (P = 0.17).
Journal of Clinical Apheresis 04/2012; 27(4):200-4. · 1.93 Impact Factor
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Vittorio Pengo,
Amelia Ruffatti,
Cristina Legnani,
Sophie Testa,
Tiziana Fierro,
Francesco Marongiu,
Valeria De Micheli,
Paolo Gresele, Marta Tonello,
Angelo Ghirarduzzi,
Elisa Bison,
Gentian Denas,
Alessandra Banzato,
Seena Padayattil Jose,
Sabino Iliceto
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ABSTRACT: Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β(2)-glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval [CI], 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.
Blood 07/2011; 118(17):4714-8. · 9.90 Impact Factor
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Amelia Ruffatti, Marta Tonello,
Maria S Visentin,
Agnese Bontadi,
Ariela Hoxha,
Sara De Carolis,
Angela Botta,
Silvia Salvi,
Monica Nuzzo,
Patrizia Rovere-Querini,
Valentina Canti,
Marta Mosca,
Gorana Mitic,
Maria T Bertero,
Vittorio Pengo,
Marie C Boffa,
Angela Tincani
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ABSTRACT: To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy.
A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared.
The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies.
It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.
Rheumatology (Oxford, England) 06/2011; 50(9):1684-9. · 4.24 Impact Factor
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Thrombosis and Haemostasis 05/2009; 101(4):789-91. · 5.04 Impact Factor
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ABSTRACT: The sera of 39 patients (38 women and 1 man), 16 with limited and 23 with diffuse clinical form of systemic sclerosis (SSc), were tested for anti-centromere (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (ARA) antibodies. The presence of apoptotic cells in cultures of circulating lymphocytes was investigated using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) technique. ACAs were present in 16 (41%), ATA in 15 (38%) and ARA in 8 (21%) cases. The mean frequency of apoptotic lymphocytes was statistically higher in the ARA positive patients with respect to that in the control population (P < 0.001), in ACA (P < 0.001) and in the ATA (P < 0.001) groups. Moreover, apoptosis was distributed homogenously in ACA and ATA positive subjects, but not in the ARA patients. Our results show that there is an increase in apoptosis in the lymphocytes of ARA positive SSc patients.
Rheumatology International 01/2009; 29(8):891-5. · 1.88 Impact Factor
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ABSTRACT: Idiopathic inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM) are a group of rare autoimmune diseases, characterized by an inflammatory infiltrate within the skeletal muscle and high titer of circulating autoantibodies in the patient's serum. The etiopathogenesis of these diseases is not known and the relationship between the specific muscle involvement and the ubiquitary presence of the targeted antigens is still unclear. The enhanced expression of myositis specific autoantigens in regenerating muscle fibers from biopsies of PM and DM patients compared to normal muscle has been recently demonstrated. In order to understand whether candidate autoantigens in myositis are expressed during post-natal myogenesis, we performed immunolocalization studies of myositis specific autoantigens in skeletal muscle from newborn and adult rats. Our observations indicate the presence of myositis specific autoantigens during post-natal myogenesis, with possible implications for the induction and/or amplification of the immune-inflammatory response, in patients affected with autoimmune myositis.
Neurological Research 04/2008; 30(2):145-8. · 1.52 Impact Factor
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ABSTRACT: Five components of the anti-beta(2)-glycoprotein I (abeta(2)GPI) enzyme-linked immunosorbent assay (ELISA) (coating buffer, microplate brand, blocking buffer, dilution buffer, and conjugate) were analyzed to evaluate how they affect variability in test results. Thirty-two samples from patients with antiphospholipid syndrome (APS) positive for abeta(2)GPI IgG antibodies and three calibrators (a pool of abeta(2)GPI-positive patients, the monoclonal HCAL antibody, and a home-made calibrator) were tested. No differences with regard to the blocking step were noted. Differences were found between the neutral and basic coating buffer when HCAL was used. There were significant differences between Maxisorp and all the other brands of tested microplates. Differences were found between phosphate-buffered saline (PBS) and all the other dilution buffers examined, with exception of TRIS when HCAL or the home-made calibrator was used. There were differences between our routine conjugate and one of the other four conjugates tested when using two of the three calibrators. There were also significant differences between the routine and another conjugate analyzed when using the third calibrator. As variations in abeta(2)GPI ELISA conditions determine significant differences in the results, selecting the appropriate test variables is an important step toward abeta(2)GPI assay standardization.
Annals of the New York Academy of Sciences 09/2007; 1109:484-92. · 3.15 Impact Factor
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Transplant International 06/2007; 20(5):475-7. · 2.92 Impact Factor
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ABSTRACT: The clastogenic effects on DNA, proven by the presence of micronuclei (MN) and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in three subsets of patients with systemic sclerosis (SSc). The frequency of MN found in cultures of peripheral lymphocytes in patients with anticentromere and antitopoisomerase I antibodies was significantly higher than that in the control group. The group with anticentromere antibody showed a significantly higher frequency of MN than did the subjects with antitopoisomerase antibody (4.22% versus 2.34%, P < 0.001). Patients with anti-RNA polymerase III, instead, had a low prevalence of typical micronucleated cells (0.98%), not significantly different from that of the healthy controls (0.82%). Moreover, when MN was characterized for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase, its frequency was found to be increased in the groups with anticentromere and antitopoisomerase I antibodies with respect to that in the controls. The increase was significantly higher in the lymphocytes of the patients with anticentromere than in those with antitopoisomerase I antibody (35% versus 20.08%, P < 0.001). Nonetheless, the prevalence of unstable DNA fragments in patients with anti-RNA polymerase III antibody was low (2.05%) and not significantly different from that of the control group (1.18%). Our results indicate that there is a clastogenic effect on DNA and an interference in the protective cellular mechanisms normally stabilizing DNA breaks only in some subsets of SSc patients.
Annals of the New York Academy of Sciences 06/2007; 1108:240-8. · 3.15 Impact Factor
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ABSTRACT: A second-line treatment protocol including plasma exchange (PE) in addition to the standard therapies was scheduled and utilized in our hospital with the intent of improving the outcome of high risk pregnancies of women with primary antiphospholipid syndrome (APS). This paper chronologically reports and discusses the results obtained in these patients over a 15-year period. Between April 1991 and September 2006, 142 pregnancies of patients with APS were followed by us. Nine of these (6.3%), who did not respond to the conventional procedures or showed complications during the treatments were shifted to a PE protocol management. All these women had a history of previous thromboembolism associated to triple antiphospholipid antibody positivity. Nine pregnancies of 7 patients (2 women were treated twice) were thus followed using PE therapy, which has undergone modification over the years. In the cases studied the outcome of pregnancy varied according to the different PE therapy conditions. This study suggests that prophylactic PE treatment administered along with full anticoagulation and IVIG therapy could be a valuable therapeutic option in high risk pregnant APS women. Further studies in this type of patients are certainly warranted.
Autoimmunity Reviews 02/2007; 6(3):196-202. · 6.62 Impact Factor
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ABSTRACT: In women diagnosed as having category I primary obstetric antiphospholipid syndrome, clinical characteristics and the risk of subsequent thromboembolic events and further unsuccessful pregnancy has not been clearly documented. Women with unexplained obstetric complications and no definite autoimmune systemic diseases were tested for lupus anticoagulant (LA), IgG/IgM anticardiolipin (aCL) and IgG/IgM anti-human beta2-Glycoprotein I (abeta2GPI) antibodies and diagnosed as having primary antiphospholipid syndrome (APS) in classification category I on the basis of more than one laboratory criteria present in any combination. Characteristics at the time of diagnosis and risk factors for subsequent clinical events during a mean follow-up of 6.3 years were evaluated. Fifty-three of 600 women studied were found to fulfil obstetric criteria and had more than one positive laboratory test at the time of diagnosis. All the women were aCL and abeta2GPI positive, and 16 were also LA positive. This latter group (triple positivity) had distinct features and had more frequently experienced previous thromboembolism (OR = 122.5, 95% CI 16-957, p < 0.001). They also had an increased rate of late pregnancy loss (OR = 16.2, 95%CI 0.9-292, p = 0.01), and a higher IgG abeta2GPI titer at diagnosis (median, 25(th) and 75(th) percentile were 118, 37-962, vs. 23, 18-32, respectively, p < 0.0001). During follow-up, the rate of thromboembolic events was significantly higher in the group of women with triple positivity and/ or previous thromboembolism (OR = 57.5, 95% CI 2.7-1160, p = 0.0004) which were the only independent predictors of TE in the multivariate model. Recurrent pregnancy loss took place in seven out of 47 women who had a new pregnancy. Triple positivity and/or previous thromboembolism were again the only independent markers (OR = 34.4, 95% CI 3.5-335.1, p = 0.003) of an unsuccessful new pregnancy. In conclusion, in primary APS with pregnancy morbidity in classification category I, quite different groups of patients may be identified on the basis of laboratory tests. Triple positivity and/or a history of thromboembolism predict new TE events and new unsuccessful pregnancies.
Thrombosis and Haemostasis 09/2006; 96(3):337-41. · 5.04 Impact Factor
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ABSTRACT: The silica clotting time (SCT) is a phospholipid-dependent coagulation assay used for the laboratory diagnosis of lupus anticoagulant (LA) antibodies. The sensitivity and specificity of a new commercial SCT for identifying LA in patients who meet the clinical criteria for antiphospholipid syndrome (APS), and its association with thrombotic events were evaluated here. Forty-five patients who met the clinical criteria for APS according to the Sapporo International Consensus Statement were examined. Sixty-nine patients who did not meet the clinical criteria for APS, and 20 blood donors were used as controls. Plasma samples from the patients and controls were tested for LA using a new commercial SCT with low and high synthetic phospholipid concentrations. The results were compared with those obtained by diluted Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT). SCT's sensitivity for identifying LA in patients who met the clinical criteria of APS was higher compared to APTT and dRVVT (53.3% vs. 31.1% and 31.1%), and the specificities of these assays were 96.6%, 100%, and 98.9%, respectively. When dRVVT was combined with SCT, and dRVVT was combined with APTT their sensitivities were 57.7% and 48.8%, and their specificities were 96.6% and 98.9%, respectively. A stepwise logistic regression analysis indicated that the combination of dRVVT with SCT was associated with total thrombotic events (odds ratio (OR)=11.5, 95% confidence interval (CI)=1.25-106.3, P=0.031) as well as with venous thrombosis (OR=4.09, 95% CI=1.16-14.43, P=0.028). According to our results, SCT is the most sensitive assay for identifying LA in patients who meet the clinical criteria for APS. Moreover, the highest sensitivity was reached with a combination of SCT and dRVVT. The method's association with total thrombotic events and venous thrombosis was in fact significant.
Journal of Clinical Laboratory Analysis 01/2006; 20(1):15-8. · 1.38 Impact Factor
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Arthritis & Rheumatism 06/2005; 52(5):1623-5; author reply 1625-6. · 7.87 Impact Factor
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ABSTRACT: To investigate the sensitivity and specificity of anti-alpha-fodrin antibodies in patients with primary Sjögren's syndrome (pSS).
IgA and IgG anti-alpha-fodrin antibodies were measured in the sera of 80 patients with pSS, 60 blood donors matched for age and sex, 50 patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA), 20 with systemic sclerosis (SSc), and 10 with polymyositis or dermatomyositis (PM/DM) by an ELISA method employing recombinant human alpha-fodrin as antigen.
The sensitivity of IgA and IgG anti-alpha-fodrin antibodies for pSS was 32.50% and 21.25%, respectively. When the prevalence of these antibodies in patients with SLE, RA, SSc, and PM/DM was evaluated, we observed specificity of these antibodies of 68.18% and 79.09%, respectively. The sensitivity and specificity for pSS of the combined determination of IgA and IgG anti-alpha-fodrin antibodies were 40% and 58.18%, respectively.
The prevalences of IgA and IgG anti-alpha-fodrin antibodies in our patients with pSS and other chronic autoimmune diseases have induced us to doubt their use as diagnostic markers of pSS.
The Journal of Rheumatology 04/2004; 31(3):504-7. · 3.69 Impact Factor
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ABSTRACT: We evaluated the prevalence and clinical significance of proteinase 3 (PR3-) and myeloperoxidase (MPO-) antineutrophil cytoplasmic antibodies (ANCA) in 115 patients with systemic sclerosis (SSc, scleroderma).
Sera were assayed by 2 independent centers, which used indirect immunofluorescence (IIF) and direct ELISA as screening tests. Inhibition-ELISA for PR3- and MPO-ANCA and PR3 capture-ELISA experiments were also performed. The clinical features of the ANCA positive were compared with those of the ANCA negative scleroderma patients.
The IIF test revealed 5 P-ANCA positive sera (4.34%). Surprisingly, by ELISA 2 of these were PR3-ANCA positive, one was MPO-ANCA positive, and 2 were both PR3- and MPO-ANCA positive. In addition, 3 IIF negative sera were ELISA positive, 2 for PR3- and one for MPO-ANCA. ELISA results were confirmed by fluid phase inhibition experiments. Only 2 out of the 6 PR3-direct ELISA positive sera were positive by PR3-capture ELISA at low titers. Neither PR3- nor MPO-ANCA were significantly associated to any clinical feature of patients with SSc.
As well as the previously described MPO-ANCA, even PR3-ANCA may be detected in some sera from patients with SSc. The IIF pattern and the negative results obtained with PR3-capture ELISA suggest that different epitopes from those recognized by vasculitis sera might be involved with PR3-ANCA in SSc, and show the importance of combining IIF and ELISA tests for ANCA detection.
The Journal of Rheumatology 06/2002; 29(5):918-23. · 3.69 Impact Factor
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ABSTRACT: The clastogenic effects on DNA, proven by the presence of micronuclei (MN), and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in patients with systemic sclerosis (SSc). The frequency of micronucleated cells found in cultures of peripheral lymphocytes in patients was significantly higher than in the control group. The patient group with anti-centromere antibodies showed a significantly higher frequency of micronucleated cells than that observed in the patients with anti-topoisomerase I antibodies (4.22% versus 2.34%, p < 0.001). Moreover, we attempted to characterize MN for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase. It was found that the frequency of MN containing DNA fragments with 3'-OH free ends (unstable fragments) increased in SSc patients compared to that observed in the control group. Moreover, this increase was significantly higher in lymphocytes of the patients with anti-centromere antibodies than in those with anti-topoisomerase I antibodies (35% versus 20.08%, p < 0.001). Our results indicate that in SSc patients there is an interference in the protective cellular mechanisms, normally stabilizing DNA breaks.
European journal of dermatology: EJD 16(3):258-61. · 2.53 Impact Factor
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ABSTRACT: Autoantibodies directed against intracellular antigens can be detected by immunoblotting (IB). Due to its high sensitivity this technique has many advantages, but it can give misleading results when the specific bands are weak or blurred against the background staining. To decrease background staining, non-ionic detergents (Tween 20, Triton X-100, Nonidet P-40) are generally used as blocking agents. Moreover, these agents appear to have a renaturating action towards proteins and antigens. Tween 20 has a more pronounced renaturating effect on proteins than other detergents and thereby improves antigen–antibody binding. To evaluate the effect of Tween 20 on specific autoantibody detection by IB, we tested the sera of 162 patients with connective tissue diseases (CTDs) by adding this detergent at certain steps of the IB assay. We found that the use of Tween 20 in the IB procedure significantly improved the binding of autoantibodies to Jo-1, Scl70, (U1)RNP 68 kDa and C, Sm B/B′ and D. Moreover, it increased the sensitivity for the detection of anti-Sm D peptide in systemic lupus erythematosus (SLE) sera with no decrease in specificity. In contrast, the addition of Tween 20 significantly decreased the binding of autoantibodies specific for ribosomal P proteins, La/SSB, Ro/SSA, but not the overall sensitivity and specificity of the method. We conclude that the addition of Tween 20 to standard IB is advantageous for anti-nuclear antigen antibody detection and improves the sensitivity of the method in revealing anti-Sm-positive sera in SLE. However, Tween 20 is not recommended for the detection of anti-cytoplasmic antibodies.
Journal of Immunological Methods.
