IgG Anticardiolipin Antibodies Research Articles

Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to disease manifestations, damage and antiphospholipid antibodies.

Background Attempts are ongoing to unveil unresolved queries about anti-double-stranded deoxyribonucleic acid (anti-dsDNA), their precise pathogenic effects and to what extent blocking them would be a useful therapeutic goal. Objectives The aim of the present study was to determine the anti-dsDNA antibodies titre in systemic lupus erythematosus (SLE) patients and investigate their relation to the disease characteristics, activity, damage and antiphospholipid autoantibodies (aPL). Methods Seventy female SLE patients and 35 age- and sex-matched controls were included. The anti-dsDNA level and aPL were measured. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) were assessed. Results The mean age of the patients was 27.5 ± 5.1 years, disease duration 7.7 ± 5.4 years, and SLEDAI and SLICC/ACR-DI scores were 6.8 ± 8.04 and 1.2 ± 1.3, respectively. Anti-dsDNA was positive in 61.4% of the patients and the titre (133.2 ± 100.5 IU/ml) was significantly higher compared to controls (22.03 ± 17.2 IU/ml) ( p < 0.0001). The anti-dsDNA level was significantly increased in those with musculoskeletal manifestations ( p = 0.007) and positive anti-β2 glycoprotein (anti-β2GP) ( p = 0.037) and decreased in those with neuropsychiatric manifestations ( p = 0.004) and those receiving cyclophosphamide (CYC) ( p = 0.013). The anti-dsDNA level tended to be higher in active patients. The anti-dsDNA titre significantly correlated with the erythrocyte sedimentation rate ( p = 0.001), anticardiolipin IgG and IgA antibodies ( p = 0.008) and anti-β2GP IgG ( p = 0.03) and IgA ( p = 0.002) and inversely with the total leucocytic count ( p < 0.0001) and SLICC/ACR-DI ( p = 0.001). Conclusion Anti-dsDNA is remarkably increased in SLE patients especially those with musculoskeletal manifestations and aPL. A protective role seems likely in those with neuropsychiatric manifestations and those receiving CYC and may form a shield against disease tissue damage.

Cardiolipin activates antigen-presenting cells via TLR2-PI3K-PKN1-AKT/p38-NF-kB signaling to prime antigen-specific naïve T cells in mice.

Mitochondrial defects and antimitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates APCs as a damage-associated molecular pattern to prime antigen-specific naïve T cells, which is crucial for T-cell-dependent anticardiolipin IgG antibody production in autoimmune diseases is unelucidated. Here, we show that CL increases the expression of costimulatory molecules in CD11c+ APCs both in vitro and in vivo. CL activates CD11c+ APCs via TLR2-PI3K-PKN1-AKT/p38MAPK-NF-κB signaling. CD11c+ APCs that have been activated by CL are sufficient to prime H-Y peptide-specific naïve CD4+ T cells and OVA-specific naïve CD8+ T cells. TLR2 is necessary for anti-CL IgG antibody responses in vivo. Intraperitoneal injection of CL does not activate CD11c+ APCs in CD14 KO mice to the same extent as in wild-type mice. CL binds to CD14 (Kd = 7 × 10-7 M). CD14, but not MD2, plays a role in NF-kB activation by CL, suggesting that CD14+ macrophages contribute to recognizing CL. In summary, CL activates signaling pathways in CD11c+ APCs through a mechanism similar to gram (+) bacteria and plays a crucial role in priming antigen-specific naïve T cells.

Hydralazine-associated vasculitis: Overlapping features of drug-induced lupus and vasculitis.

Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record. 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography. Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition.

Ophthalmological and medical long-term follow-up of patients with central retinal vein occlusion

Purpose: The purpose of this study was to evaluate the ophthalmological and medical aspects of patients with a history of central retinal vein occlusion (CRVO) after a long-term follow-up. Design: This was a retrospective case–control study. Materials and Methods: Twenty-seven consecutive CRVO patients (29 eyes) were enrolled between April 2011 and April 2012, each participant underwent a comprehensive and detailed interview and also they had an ophthalmic examination with investigations such as color retinography and optical coherence tomography. Finally, medical and cardiologic examinations, including the laboratory analysis of blood specimens, were performed to all participants. Results: Our data confirm the significant association of CRVO with age (P = 0.025) and with ischemia (P = 0.022) and also treatment with low-molecular-weight heparin. Main risk factors of developing CRVO were as follows: hypertension (59.0%), dyslipidemia (48.0%), blood diseases (15.0%), and high body mass index (15.0%). There was no any significant association between all of the thrombophilic factors (laboratory parameters) and visual acuity (VA), except IgG anticardiolipin antibodies (P = 0.004). Two patients had myocardial infarction during the follow-up period. There was a parallel reduction of VA and foveal thickness during a long follow-up period. Conclusions: VA and central foveal thickness decreased during the follow-up period probably because of a progressive atrophy of the central retinal area, which suggest an early treatment of the macular edema prior an unfavorable evolution of the clinical situation, only one laboratory parameter had association with VA, small minority of patients developed serious cardiovascular events during the follow-up period after CRVO; these data suggest no overall association of CRVO with cardiovascular events.

Can thrombophilia worsen maternal and perinatal outcomes in cases of severe preeclampsia?

To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE). From October 2009 to October 2014, an observational retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. New pregnancies of the same patient; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes. Of the 127 patients selected, 30 (23.6%) had thrombophilia (hereditary or acquired). We found more white patients in thrombophilia group (p = .036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = .056) and showed worsening of composite laboratory abnormalities (aspartate aminotransferase ≥ 70 mg/dL, alanine aminotransferase ≥ 70 mg/dL, platelets < 100,000/mm3, serum creatinine ≥ 1.1 mg/dL; p = .017). There were no differences in foetal perinatal outcomes. The presence of thrombophilia leads to worsening of maternal laboratory parameters among patients with severe forms of PE but without worsening perinatal outcomes.

Association between false-positive TORCH and antiphospholipid antibodies in healthy pregnant women.

The present study investigated: (a) the presence of antiphospholipid antibodies and (b) the obstetric outcome in healthy pregnant women showing false-positive TORCH-Toxoplasmosis, Other: syphilis, varicella-zoster, Rubella, Cytomegalovirus (CMV), and Herpes infections-results. Data from 23 singleton healthy pregnancies with false-positive TORCH results were collected. Each woman was systematically screened for TORCH IgG and IgM during the pre-conception assessment and/or at the beginning of pregnancy. In the presence of IgM positivity, when indicated (CMV, toxoplasmosis, rubella, herpes simplex virus), IgG avidity was evaluated and, if possible, polymerase chain reaction was performed on an amniotic fluid sample in order to distinguish between primary infection or false positivity. The antiphospholipid antibodies tests were: lupus anticoagulant, anticardiolipin antibodies IgG, IgM, and anti-β2glicoprotein I IgG, IgM. The antiphospholipid antibodies tests, if positive, were repeated after 12 weeks to confirm the results. In pregnant women with false-positive TORCH, the overall prevalence of positive antiphospholipid antibodies for one or more tests was 52.2%. To clarify the correlation of false-positive TORCH results with clinical practice, obstetric outcome was analyzed in terms of live births, week of delivery, neonatal birth weight, and neonatal birth weight percentile. A statistically significant lower neonatal birth weight and neonatal birth weight percentile were observed in women with false-positive TORCH associated with antiphospholipid antibodies positivity (Group A) in comparison with those in women with false-positive TORCH without antiphospholipid antibodies positivity (Group B). No statistically significant difference was found for the week of delivery between the two groups. It is hoped that future studies will verify the life-long persistence of antiphospholipid antibodies positivity by follow-up of these women and identify who will develop a classical antiphospholipid syndrome or other autoimmune disorders.

CLINICAL SIGNIFICANCE OF N-TERMINAL FRAGMENT OF NATRIURETIC PEPTIDE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS WHO DO NOT RECEIVE PATHOGENETIC THERAPY

Objective: to determine the level of the N-terminal fragment of brain natriuretic peptide progenitor (NT-proBNP) in patients with systemic lupus erythematous (SLE) prior to immunosuppressive therapy and its possible association with inflammatory markers, traditional risk factors (TRFs) for cardiovascular diseases (CVD), and transthoracic echocardiographic (EchoCG) parameters.Subjects and methods. The investigation enrolled 28 SLE patients fulfilled the 1997 ACR criteria, including 23 (82%) women (median age, 28.5 [25.0; 32.0] years), who had no clinical signs of CVD and received no immunosuppressive therapy. A control group consisted of 27 age-and sex-matched healthy donors. Disease activity was assessed by SLEDAI-2K; irreversible damages were measured using SLICC. The median duration of SLE was 21.0 [5.0; 60.0] months, the scores of SLEDAI-2K and SLICC/DI were 11 [8; 19] and 0 [0; 0], respectively. The investigators estimated the concentration of Creactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), carried out EchoCG, and assessed TRFs. The serum concentration of NT-proBNP was determined by electrochemiluminescence (Roche Diagnostics, Switzerland). The normal range for NT-proBNP was ≤125.0 pg/ml. Results and discussion. The patients with SLE had elevated levels of NT-proBNP compared with the controls: 160.7 [88.6; 335.4] and 55.2 [36.6; 70.3] pg/ml, respectively (p &lt; 0.001). The patients were divided into two groups: 1) 18 (64%) patients had a NT-proBNP concentration of &gt; 125.0 pg/ml; 2) 10 (36%) patients had no more than this level. As compared with Group 2, Group 1 had the elevated values of IgG anti-cardiolipin (aCL) antibodies (p &lt; 0.01), creatinine (p &lt; 0.05), left ventricular (LV) end-systolic dimension (ESD) (p &lt; 0.05) and decreases in LV ejection fraction (EF) (p &lt; 0.01), glomerular filtration rate (GFR) (p &lt; 0.05), and concentration of anti-Ro antibodies (p &lt; 0.05). In all the patients (n = 5 (18%)) with LV diastolic dysfunction (DD), the NT-proBNP level was much higher than normal; its median was 799.2 [276.6; 1777.0] pg/ml, but no statistically significant differences were found in the frequency of LV DD between the groups (p = 0.066). In the patients with SLE, the NT-proBNP level correlated positively with that of creatinine (r = 0.480; p &lt; 0.01), uric acid (r = 0.427; p &lt; 0.05), IgG aCL (r = 0.710; p &lt; 0.001), anti-double-stranded DNA (anti-dsDNA) antibodies (r = 0.395; p &lt; 0.05), antinuclear antibodies (ANA) (r = 0.256; p &lt; 0.05), LV ESD (r = 0.442; p &lt; 0.05), pulmonary artery systolic pressure (r = 0.486; p &lt; 0.05) and negatively with hemoglobin level (r = -0.493; p &lt; 0.01), C4 complement component (r = -0.475; p &lt; 0.05), GFR (r = -0.58; p &lt; 0.01), and EF (r = -0.505; p &lt; 0.01). The level of NT-proBNP was ascertained to be unassociated with the clinical manifestations of SLE (skin, mucosae, kidneys, nervous system damage, as well as arthritis, serositis, and hematological disorders) and markers of inflammation (CRP, IL-6, TNF-α).Conclusion. The NT-proBNP concentration in the patients with SLE was significantly higher than in the control group (p &lt; 0.001), more than 60% of the untreated SLE patients had elevated NT-proBNP values (&gt;125.0 pg/ml). The higher level of NT-proBNP is associated with the immunological parameters of SLE activity (elevated values of IgG aCL, anti-dsDNA, and ANA as well as C4 hypocomplementemia) and with the markers that reflect deterioration in renal and myocardial functions. There was no relationship of NT-proBNP levels to the clinical manifestations of SLE and the markers of inflammation (CRP, IL-6, and TNF-α) and TRFs.

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.

Effects of statins on thrombosis development in patients with systemic lupus erythematosus and antiphospholipid antibodies.

The objective of this study is to identify the effects of statins and risk factors for thrombosis in patients with new onset of systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL). Consecutive patients with SLE without history of thrombotic events were retrospectively enrolled from April 1997 to February 2014. The development of first thrombosis and death caused by thrombosis were defined as the study endpoint. Risk and protective factors for developing thrombosis were analyzed. A total of 152 patients, 80 positive and 72 negative for aPL, were included. In aPL-positive patients, 15 developed arterial ( n = 6) and venous ( n = 9) thrombosis (median follow-up period 69 months). Cox's proportional hazards model showed that older age at SLE onset and IgG-anticardiolipin antibodies (aCL) were statistically significant risks for thrombosis. Statin therapy was identified as a statistically significant protective factor against thrombosis (hazard ratio 0.12, 95% confidence interval 0.01-0.98). In aPL-negative patients (median follow-up period 46 months), seven patients developed thrombosis (five arterial and two venous). No risk factors for thrombosis were found in this group. In aPL-positive patients with SLE, the late disease onset and the presence of IgG-aCL represented additional risk factors for thrombosis. Statin treatment appeared as a protective factor for thrombosis.

Subclinical myocardial dysfunction by tissue Doppler echocardiography in primary antiphospholipid syndrome: Preliminary results

Aim of the workTo preliminary evaluate the myocardiac function in asymptomatic primary antiphospholipid syndrome (PAPS) patients using conventional and tissue Doppler echocardiogram. Patients and methodsNine female PAPS patients asymptomatic for cardiac manifestations and 7 matched controls were enrolled. Myocardial function was determined by echocardiogram (conventional and tissue Doppler imaging ‘TDI’ techniques). ResultsThe median age of the patients was 43 (26–55years) and disease duration 10 (3–19)years. Traditional cardiovascular risk factors were similar in PAPS and controls. Venous and arterial events were present in 55.6%, 22.2% showed obstetric features, 33.3% had stroke, 44.4% deep venous thrombosis and 66.7% had livedo reticularis. All patients were under oral anticoagulants with international normalization ratio within therapeutic range (2–3). 88.9% were positive for IgG and/or IgM anticardiolipin antibodies and 66.7% were positive for lupus anticoagulant. Conventional echocardiographic data were not altered in all evaluated parameters comparing patients and controls. Regarding TDI, a lower S’ (systolic wave which is related to systolic function in the analysed segment) of lateral wall of left ventricle was observed in PAPS in comparison to controls [0.085 (0.007–0.12) vs. 0.12 (0.09–0.13), p=0.004] as well as A′ wave of the septum (related to late diastolic function in the analysed segment) [0.07 (0.06–0.08) vs. 0.09 (0.07–0.11), p=0.02]. ConclusionThe present study demonstrated subclinical myocardial dysfunction using TDI in asymptomatic PAPS patients. TDI is non-invasive and cost effective. Prospective studies including a large number of participants in order to confirm these preliminary data are needed.

Antiphospholipid antibodies can identify lupus patients at risk of pulmonary hypertension: A systematic review and meta-analysis.

Pulmonary hypertension (PH) is a life-threatening condition that may affect outcomes in patients with systemic lupus erythematosus (SLE). The role of antiphospholipid antibodies (aPL) on the risk of PH is controversial. Therefore our objective was to estimate the risk of PH (WHO groups 1-5) including associated pulmonary arterial hypertension (APAH, WHO group 1 only) related to aPL in patients with SLE. Systematic review and meta-analysis were performed: MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched through 2015. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (PH including APAH). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. PROSPERO registration number: CRD42015016872. Of 984 identified abstracts, 31 primary studies (five cohorts, 13 case-control, 13 cross-sectional) met inclusion criteria, including 4480 SLE patients. Prevalence of PH in aPL-positive vs. aPL-negative SLE patients was 12.3% vs. 7.3%, respectively. The overall pooled odds ratio (OR) for PH was 2.28 (95% CI, 1.65 to 3.15) (I2=39%). The risk of APAH was also significantly increased (OR=2.62 [95% CI, 1.11-6.15]). The risk of PH was the highest for lupus anticoagulant (OR=1.96 [95% CI, 1.31-2.92]) and IgG anticardiolipin antibodies (OR=2.64 [95% CI, 1.30-5.36]) while other antibodies were not significantly associated with PH. Among SLE patients, aPL can identify patients at risk for PH and APAH. These findings warrant implementation of effective screening and early treatment strategies.

Clinical relevance of antiphospholipid antibodies in systemic sclerosis: A systematic review and meta-analysis.

To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in systemic sclerosis (SSc). A systematic search of EMBASE and PubMed databases from January 1983 to July 2016 was carried out according to PRISMA guidelines whereas Peto׳s odds ratio (OR) for rare events was used for the meta-analysis. The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) antibodies was higher in SSc than controls (12.8% vs 1.6% and 7.8% vs 0.6%; p < 0.0001 for both) as was that of IgG and IgM anti-beta-2-glycoprotein-I antibodies (aβ2GPI) (6.1% vs 0.58%, p < 0.0001; 3.5% vs 0.3%, p = 0.001). The pooled prevalence of pulmonary arterial hypertension (PAH) was more common in SSc positive than negative patients for aCL (IgG/IgM combined) (26.5% vs 10.9%, p < 0.0001) whereas the pooled prevalence of renal disease (RD) was more common in IgG aCL positive than negative patients (36.3% vs 10.9%, p = 0.02). The pooled prevalence of thrombosis was higher in IgG aCL, IgM aCL, and IgM aβ2GPI positive than negative SSc patients (12.6% vs 1.4%, p < 0.0001), (15.1% vs 2.7%, p = 0.002) and (15% vs 0.78%, p = 0.009), respectively. The pooled prevalence of digital infarction/ischemia (DI) was higher in IgG aCL and IgM positive than negative SSc (52.8% vs 39.8%, p = 0.002) and (68.1% vs 29%, p = 0.07). A strong relationship exists between aCL and aβ2GPI of IgG/IgM isotype and SSc; patients positive for these antibodies are more likely to suffer from PAH, RD, thrombosis, and DI. However, data expressed as frequency of aPL positive patients rather than average antibody titers preclude further insight into the relevance of these assumptions.

Familial primary antiphospholipid syndrome: A report of co-occurrence in three Malaysian family members.

Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.

Simultaneous Quantification of Anticardiolipin IgG and IgM by Time Resolved Fluoroimmunoassay.

The autoimmune disease antiphospholipid syndrome (APS) is characterized by the presence of anticardiolipin antibodies (aCL), along with anti-β2-glycoprotein I (β2GPI) antibodies and lupus anticoagulant (LA). In this study, we developed a time-resolved fluoroimmunoassay (TRFIA) system for simultaneous quantification of aCL IgG and IgM. A 96-well microtiter plate precoated with the complex of cardiolipin from bovine heart and bovine β2GPI was incubated with the anticardiolipin IgG and IgM standard substance or serum, and the conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM was pipetted to the wells to form a tipical double-antibody-sandwich immunoreactions; finally the fluorescent intensity of Eu3+ and Sm3+ was detected to reflect the quantity of anticardiolipin IgG and IgM. This assay showed a good relationship between fluorescence intensities and the concentration of anticardiolipin antibody(aCL) IgG and IgM, with a low-end sensitivity of 0.1 U/ml for IgG and 0.1 U/ml for IgM, respectively. The intra- and inter-assay coefficients of variation (CV) of the calibrators was 3.0% and 4.51% for IgG, and 2.76% and 4.45% for IgM. The average recovery was 100.38% for aCL IgG and 100.45% for aCL IgM. For serum samples, the results of our method showed a good correlation with those obtained with ELISA kit. Simultaneous detection of aCL-IgG and aCL-IgM in the same reaction well can optimize assay performance by avoiding potential influence of different reaction conditions-timing, and well-to-well difference in concentration and characteristics of cardiolipin antigen. The results of a combo aCL-IgG and aCL-IgM assay for the same sample are more consistent and more reliable. This dual-label time-resolved fluoroimmunoassay is sensitive for detecting aCL IgG and IgM across a wide concentration range with stable reagents and may assist in the clinical diagnosis of antiphospholipid syndrome.

Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study

The aim of this multicenter study was to assess the present risk of fetal complications and the inherent risk factors in pregnant women with lupus nephritis.Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were prospectively followed between October 2006 and December 2013. All patients received a counselling visit within 3 months before the beginning of pregnancy and were followed by a multidisciplinary team. At baseline mild active nephritis was present in 15 cases (21.1%).Six pregnancies (8.4%) resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007), antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid antibodies (P = 0.004) predicted fetal loss.Twenty pregnancies (28.2%) ended pre-term and 12 newborns (16.4%) were small for gestational age. Among the characteristics at baseline, high SLE disease activity index (SLEDAI) score (P = 0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the probability of preterm delivery. Odds for preterm delivery increased by 60% for each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in proteinuria by 1 g per day. The probability of having a small for gestational age baby was reduced by 85% in women who received hydroxychloroquine therapy (P = 0.023).In this study, the rate of fetal loss was low and mainly associated with the presence of antiphospholipid antibodies. Preterm delivery remains a frequent complication of pregnancies in lupus. SLE and lupus nephritis activity are the main risk factors for premature birth. Arterial hypertension predicted both fetal loss and preterm delivery.Based on our results the key for a successful pregnancy in lupus nephritis is a multidisciplinary approach with close medical, obstetric and neonatal monitoring. This entails: a) a preconception evaluation to establish and inform women about pregnancy risks; b) planning pregnancy during inactive lupus nephritis, maintained inactive with the lowest possible dosage of allowed drugs; c) adequate treatment of known risk factors (arterial hypertension, antiphospholipid and antibodies); d) close monitoring during and after pregnancy to rapidly identify and treat SLE flares and obstetric complications.

Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling.This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes.Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP.In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

Systemic lupus erytherymatosus: an interdisciplinary approach to the diagnosis

Diagnosis of systemic lupus erythematosus presents certain difficulties up to now. Due to the prognostic significance of the disease and the need to early pathogenetic treatment clinical cases of SLE are described. Questions of modern differential diagnosis are reviewed. If skin changes are presented a positive test for antinuclear antibodies helps to detect SLE timely. 4 clinical cases of women with systemic lupus erythematosus are presented. Diagnostics required comprehensive examination with histopathological and immunological studies: blood test antinuclear factor on HEp-2 cells with the definition of lupus anticoagulant in blood plasma, rheumatoid factor, anticardiolipin antibody IgG and IgM, double stranded DNA, antinuclear antibody IgG, auto antibodies to IgG AMA-M2 (immunoblott), cardiolipin antibodies and lupus anticoagulant.

A male patient with myocardial infarction as a first manifestation of antiphospholipid syndrome — treatment with rivaroxaban

Data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) in the antiphospholipid syndrome (APS) are not clear. We present a case of a male patient aged 34 years with a history of myocardial infarction at the age of 25 treated conservatively, at that time associated with the risk factors including arterial hypertension, cigarette smoking, hypercholesterolaemia, and overweight. The notable laboratory finding observed for the first time was prolonged activated partial thromboplastin time (aPTT). At the age of 32 the patient experienced left-sided distal thrombosis of the lower limb and ischaemic stroke. The prolonged aPTT was further evaluated. APS testing was performed revealing the positive lupus anticoagulant, elevated anticardiolipin IgG antibodies and b-2-glicoprotein I IgG antibodies. Anticoagulant therapy with warfarin was initiated. Due to the disadvantages of the need for international normalised ratio monitoring, the treatment with rivaroxaban 20 mg daily was implemented according to the patient’s preferences. The patient has been taking the rivaroxaban for 15 months and has not experienced the recurrent venous and arterial thromboembolism. This case confirms that patients with APS who experienced arterial thrombosis may benefit from treatment with NOAC. Moreover, it emphasises the need for thrombophilia screening in patients aged 50 years and younger following the myocardial infarction, especially below 30 years even in the presence of cardiovascular risk factors. Recurrent thrombotic events following myocardial infarction, especially in the absence of coronary artery stenosis, should prompt search for acquired thrombophilia, especially APS, which predisposes to venous thromboembolism and ischaemic stroke.

Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies.

We evaluated analytical and clinical performances of IgG and IgM anticardiolipin (aCL) antibodies and anti-β2-glycoprotein I (a-β2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer's cutoff values with different commercial methods. We assayed aCL and a-β2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome (APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases, using ELISA Inova Diagnostics; EliA Phadia Laboratory Systems; CliA Zenit-RA; and CliA Bio-Flash. Anticardiolipin and a-β2GpI IgG and IgM immunoassays showed good analytic performances with both 99th percentile and manufacturer's cutoff reference values. Our results showed fair to moderate agreement among assays. In-house cutoff values gave significantly better performances only for a-β2GpI IgG with all the immunoassays analyzed with the exception of Inova CliA Bio-Flash where we obtained the same performances with in-house and manufacturer's cutoffs. By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low-positive, medium-/high-positive, and high-positive CliA IgG aCL and a-β2GpI ranges in order to help clinicians in the diagnosis and treatment of APS.

Aneurysmal Subarachnoid and Spinal Hemorrhage Associated With Systemic Lupus Erythematosus

A 42-year-old woman with systemic lupus erythematosis (SLE), positive lupus anticoagulant, elevated titers of IgG and IgM anticardiolipin antibody and β2 glycoprotein antibodies, idiopathic thrombocytopenia, and hemolytic anemia presented with menorrhagia and anemia. She received both platelet and red cell transfusions and had an unrevealing endometrial biopsy. She was treated with intravenous immunoglobulin therapy for autoimmune-mediated thrombocytopenia and was taking hydroxychloroquine 200 mg twice daily that was a home medication. She was started on prednisone 60 mg daily. During her hospitalization, she developed a sudden, severe, sharp, and pounding occipital and nuchal headache with sharp shooting pains radiating down the back of the neck. She was alert and oriented with normal cranial nerve function, motor strength, and sensation. Her headache was unsuccessfully treated with fioricet and acetaminophen. The day after headache onset, a noncontrast head computed tomography revealed a subarachnoid hemorrhage (SAH) extending from the interpeduncular fossa caudally to the cervicomedullary junction (Figure 1). Computed tomographic angiogram of the head and neck revealed a focal left vertebral artery stenosis with poststenotic aneurysmal dilation of the intradural (V4) segment. There were additional multifocal areas of beading and long tapered vessel narrowing involving the M2 division of the left middle cerebral artery and anterior cerebral arteries and M3 division of the right middle cerebral artery (Figure 1). Magnetic resonance brain demonstrated multifocal but posteriorly predominant T2 hyperintense lesions that resembled posterior reversible leukoencephalopathy syndrome (Figure 2). Conventional angiogram confirmed the global small and medium vessel vasculopathy with a left V4 vertebral artery fusiform aneurysm measuring 10.6 mm×5.5 mm distal to the origin of the left posterior inferior cerebellar artery (Figure 2). Figure 1. Lupus-associated central nervous system vasculitis and subarachnoid hemorrhage (SAH). A , Computed tomographic (CT) head demonstrating perimedullary SAH (black arrow). B , CT angiogram demonstrating focal stenosis of the intracranial …