bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus
Authors: Martini F. , Farsi A. , Gori AM , Boddi M. , Fedi S. , Domeneghetti MP , Passaleva A. , Prisco D. , Abbate R. 
Published: November 2007

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet. Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasmin ogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL ( p < 0.01) and to controls ( p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.
Long term follow-up of children with mixed connective tissue disease
Authors: Mier R. , Ansell B. , Hall MA , Hasson N. , Levinson J. , Lovell D. , Passo M. , Rennebohm R. , Woo P. 
Published: November 2007

Mixed connective tissue disease (MCTD) is characterized by features of more than one of the rheumatic disorders with antinuclear antibodies in a speckled pattern and with anti bodies to nuclear ribonucleoprotein (nRNP). MCTD is uncommon in children and long- term follow-up studies in children are infrequently reported. A retrospective review of clinical experience at five pediatric rheumatology centers provided 11 patients who met the following inclusion criteria: (1) Kasukawa's criteria for MCTD1; (2) presentation younger than 18th birthday; (3) greater than five years of follow-up; (4) completion of data collection form. The widely varying outcomes of these 11 children with MCTD on long-term follow-up may lend doubt that this is a unique and distinctive rheumatologic disorder.
Controlled trial with chloroquine diphosphate in systemic lupus erythematosus
Authors: Meinão IM , Sato EI , Andrade Lec , Ferraz MB , Atra E. 
Published: November 2007

Introduction: Antimalarials have been recognized as effective drugs for the treatment of articular and cutaneous manifestations of systemic lupus erythematosus (SLE), but its potential in the management of systemic features of the disease has not yet been thoroughly evaluated. Objectives: This study intended to evaluate the efficacy of chloroquine diphosphate (CDP) in preventing flares and in reducing the maintenance corticosteroid dose in patients with SLE without life-threatening manifestations. Materials and methods: Twenty-four SLE patients with no life-threatening manifestation were enrolled in a 12-month double blind placebo-controlled trial with CDP (250 mg/day). Patients were subjected each month to clinical examination by a rheumatologist and to SLE-relevant laboratory tests. At each visit, prednisone dose could be adjusted according to the clinical status. Ophthalmologic examination was performed every six months. Outcome measures included SLEDAI score and the required prednisone dose. SLE flare was defined as an increase in SLEDAI score of at least three points. Prednisone dose reduction was defined as a minimum 50% dose decrease with no concomitant disease flare. Results: Twenty-three patients completed the study. One patient in the placebo (PL) group dropped out due to severe dyspepsia. No major side-effect was observed in the remaining patients. PL and CDP groups showed no significant difference at the beginning of the study with regard to sex, age, ethnic classification, disease duration, SLEDAI and prednisone dose. Along the trial the prednisone dose became progressively lower in CDP group as compared to PL group and the difference reached statistical significance at 4, 6 and 12 months. SLEDAI score was higher in PL group in all evaluations, being the difference statistically significant at 4 months. Flare-up episodes were registered in two patients in CDP group and in ten patients in PL group. The estimated reactivation risk was 4.6 times greater in PL group as compared to CDP group. Conclusions: CDP at a 250 mg/day dose was able to prevent disease exacerbation, reduce the required prednisone dose, and help inducing a better control of patients with non life- threatening SLE. These data suggest that antimalarials might have a broader indication in the treatment of SLE other than solely the management of skin and articular manifesta tions.
Review : Photosensitivity in systemic lupus erythematosus: laboratory testing of ARA/ACR definition
Authors: Doria A. , Biasinutto C. , Ghirardello A. , Sartori E. , Rondinone R. , Piccoli A. , Veller Fornasa C. , Gambari PF 
Published: November 2007

Objective. The aim of our study was to evaluate the prevalence of photosensitivity in SLE as defined by either clinical or laboratory assessment, the concordance of findings obtained by two methods, and the relationship between photosensitivity and clinical and immunological parameters. Methods. Forty-four SLE patients and 31 healthy subjects were included. Patients and con trols underwent a standard questionnaire testing and the minimal erythemal dose (MED) measurement performed by Dermalight-Blue Point. The standard questionnaire was designed in order to meet, as near as possible, the definition of photosensitivity included in the ARA/ACR criteria for classification of SLE. Results. The prevalence of photosensitivity was (patients vs controls): 57% vs 45% accord ing to questionnaire; 79.5% vs 51.6% ( P = 0.02) according to MED. The agreement between questionnaire and phototest was absent in SLE (kappa 0.01) and poor in controls (kappa 0.36). Discoid rash was significantly associated with questionnaire positive ( P = 0.01) and renal involvement with questionnaire negative results ( P = 0.02), serositis with MED abnormality ( P = 0.03), malar rash and anti-Sm antibody with MED normal values ( P = 0.03 and P = 0.01, respectively). Moreover, by multivariate analysis, malar rash and anti-Sm antibody significantly predicted MED-defined photosensitivity, with probability ranging from 42% (presence of both) to 92% (lack of both). Conclusions. Photosensitivity is frequently observed in SLE patients as well as in healthy subjects. Its prevalence is significantly higher in SLE than in controls only when it is detected using the laboratory method. However, due to the difficulty in objectively defining such manifestation, the disagreement between questionnaire and MED results was high and its clinical meaning appears ambiguous. Thus, the use of photosensitivity as a classification criterion for SLE remains questionable, at least when it is assessed according to the ARA/ACR definition.
A cross-sectional study of anti-DNA antibodies in the serum and IgG and IgM fraction of healthy individuals, patients with systemic lupus erythematosus and their relatives
Authors: Williams WM , Isenberg DA 
Published: November 2007

Sera from healthy individuals, relatives of lupus patients, and lupus patients with active disease and in remission were screened for IgG and IgM antibodies to ssDNA and dsDNA. The serum samples were also separated into IgG and IgM fractions which were screened for DNA reactivity at dilutions equivalent to those used for testing un-fractionated serum. The results show that whilst, as expected, antibodies of IgG or IgM isotype to both ss and dsDNA could be detected in high concentration in the serum of lupus patients with active disease, anti- ssDNA antibodies of the IgG or IgM isotype are also detectable in healthy individuals, relatives and spouses of lupus patients. Furthermore when IgG and IgM serum fractions were separated and screened for DNA reactivity, the IgM fraction in the healthy individuals frequently showed an increase in the level of binding to ssDNA compared to the serum or separated IgM fraction of SLE relatives. In contrast no increase in DNA reactivity of the IgG fraction was detected in the separated IgG fraction from healthy individuals. These observations infer that IgM autoantibodies are present in healthy individuals at levels higher than is reported normally, and at levels comparable with those found in relatives of SLE patients in which autoreactive antibodies are frequently reported, and their ability to bind ssDNA in whole serum is inhibited by IgG antibodies present within whole serum.
Anti β2glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance
Authors: Ogasawara M. , Aoki K. , Matsuura E. , Sasa H. , Yagami Y. 
Published: November 2007

Anticardiolipin antibodies (aCL) were found to recognize β2glycoprotein I (β2GPI) structure altered by its interaction with an oxygen modified solid phase surface by γ-ray radiation. Lupus anticoagulant (LA) has been reported to comprise anti prothrombin antibodies, anti factor X antibodies and anti β2GPI antibodies. The present study focuses on the possible association between antibodies against the altered β2GPI structure (anti β2GPI antibodies) and LA in patients with recurrent pregnancy loss. Moreover, the clinical significance of both subgroups of so-called antiphospholipid antibodies were investigated to cast light on the controversy of whether aCL and LA are risk factors for pregnancy losses. One hundred and ninety five women with a history of two or more unexplained consecutive miscarriages and 100 control pregnant women were tested. Lupus anticoagulant was detected by the dilute phospholipid activated partial thromboplastin time. Anti β2GPI antibodies were measured by the ELISA method using commercially oxygenated microtiter plates. Twenty two (11.3%) and 19 (9.7%) of the 195 recurrent aborters were, respectively, positive for LA and anti β2GPI antibodies. Seven (3.6%) of the aborters had both of them. None of the control pregnant women had LA. Three of the control pregnant women had anti β2GPI antibodies. Nine (40.9%) of 22 aborters with positive-LA had a history of miscarriages in the second trimester as compared to 8 (4.6%) of 173 aborters with negative-LA. (P = 0.000007, Odds ratio = 14.3). None of the 12 aborters with anti β2GPI antibodies but no LA had a history of second trimester-fetal loss. These results support the hypothesis that aCL and LA define two distinct but partly related populations and that aCL include two subtypes of antibodies, with and without LA activity. LA and anti β2GPI antibodies appear to be associated with pregnancy loss, with LA being linked not only to abortions in the first trimester but also to miscarriages in the second trimester.
Diagnosis of alveolitis in interstitial lung manifestation in connective tissue diseases: importance of late inspiratory crackles, 67 gallium scan and bronchoalveolar lavage
Authors: Witt C. , Dömer T. , Hiepe F. , Borges AC , Fietze I. , Baumann G. 
Published: November 2007

The diagnostic relevance of bronchoalveolar lavage (BAL) and associated non-invasive findings in connective tissue diseases (CTD) has not been established regarding alveolitis so far. The goal of the study was to determine the relations between BAL cell differential count and findings of non-invasive diagnostic procedures for alveolitis to predict the clinical value of BAL in CTD. One hundred-five patients (92 non-smokers; 13 smokers) with CTD (73 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 13 with primary Sjögren's syndrome) had symptoms or signs of lung involvement and were further examined (lung function test, chest radiography, thoracic computed tomography, 67 gallium scintigraphy and BAL). The relations between BAL in middle lobe and cell count differentiation to non-invasive investigations were analyzed by logistic regression. In all CTD patients investigated a pulmonal involvement occurred based on non-invasive methods. Regarding non-invasive methods, alveolitis determined by BAL cell differential count was significantly associated with an increased 67-gallium uptake and late inspiratory crackles (P < 0.01), and to a lesser extent with an abnormal interstitial pattern in CT (P < 0.055). Parameters of lung function and laboratory parameters were related to alveolitis using multivariate testing. Considering the alveolities subtype (granulo- or lymphocytosis), only a reduced FEV1 showed a relationship to granulocytic alveolitis (P < 0.01). Late inspiratory crackles and increased 67 gallium uptake as non-invasive diagnostic findings point out alveolitis in CTD remarkably. Therapeutic and prognostic aspects necessitate BAL to specify the type of alveolitis (lymphocytosis or granulocytosis or mixed forms) in CTD patients with lung manifestation. Non-invasive diagnostic procedures cannot predict the type of alveolitis sufficiently.
C-fibre function in systemic lupus erythematosus
Authors: Omdal R. , Bekkelund SI , Mellgren SI , Husby G. 
Published: November 2007

Systemic lupus erythematosus (SLE) frequently involves the central nervous system (CNS), but to a considerably lesser degree leads to peripheral neuropathy as measured by conventional nerve conduction velocity studies. Neuropathic symptoms are, however, frequently reported. Abnorm alities of other nerve fibers than the large myelinated nerves might thus be responsible for such phenomena. Three age matched groups of 44 patients with SLE, 50 patients with rheumatoid arthritis (RA) and 45 healthy controls were investigated with quantitative sensory thermotesting. Warm detection thresholds (WDT) and heat pain detection thresholds (HPDT) were found significantly higher in SLE compared to RA and controls. There were no differences between the RA and the control group. In the SLE group no association to disease duration, medication or CNS abnormalities were found. Neuropathic symptoms and vibration thresholds showed weak associations to WDT. These findings imply that there is an impairment of C-fibre function in SLE. This small fibre neuropathy is probably not part of a generalized diffuse polyneuropathy also affecting large fibres, although this can not be ruled out completely by this study.
Vasculitis in systemic lupus erythematosus
Authors: Drenkard C. , Villa A.R. , Reyes E. , Abello M. , Alarcón-Segovia D. 
Published: November 2007

We studied the frequency, location, clinical and histopathological features, associated manifestations, and prognosis of vasculitides in a cohort of 667 SLE patients. Exclusion of patients with previous vasculitis or insufficient information left 540 patients, 194 of whom had vasculitis (incidence density: 0.053 new cases/person/year, cumulative incidence of 0.051 at one year, 0.232 at 5 years and 0.411 at 10 years). Vasculitis was confirmed by biopsy in 46 cases, by arteriography in five, and by both in three. A single episode of vasculitis occurred in 119 and two or more in 75 patients. Vasculitis was cutaneous in 160, visceral in 24, both in 10. In the first episode of cutaneous vasculitides, 111 had punctuate lesions, 32 palpable purpura, 6 urticaria, 6 ulcers, 8 papules, 5 erythematous plaques or macules confirmed with biopsy, 2 erythema with necrosis, and 1 panniculitis (plus small vessel vasculitis). Of 29 with visceral vasculitis in the first episode, 19 had mononeuritis multiplex, 5 digital necrosis, 3 large artery vasculitis of limbs, one mesenteric, and one coronary. More than one type could appear simultaneously or in subsequent episodes. Patients with vasculitis had longer disease duration and followup, younger age of onset of SLE, and were more frequently males than those without. Lupus manifestations associated with vasculitis in univariate logistic regression included myocarditis, psychosis, Raynaud's phenomenon, serositis, leukopenia, lymphopenia and pleuritis. Vasculitis also associated with the antiphospholipid syndrome. The strength of this association increased when patients with vasculitis confirmed by biopsy and/or arteriography were considered separately. Visceral vasculitis associated with increased mortality when controlled for age of onset and nephropathy.
Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies
Authors: Fanelli A. , Bergamini C. , Rapi S. , Caldini A. , Spinelli A. , Buggiani A. , Emmi L. 
Published: November 2007

Platelet activation has been suggested to play a crucial role in the pathogenesis of haemostatic disorders in antiphospholipid syndrome (APS). In 16 patients with primary APS (PAPS) we investigated by flow cytometry the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoproteins CD62 and CD63. In addition, the relationships among activated platelets, thrombocytopenia, antiphospholipid antibodies (aPL) and platelet associated IgG (PalgG) were evaluated. Compared to normal subjects CD62, but not CD63 expression, was found significantly increased in patients. All thrombocytopenic subjects showed a percentage of CD62 expressing platelets above the cut off. In thrombocytopenics a significantly increased percentage of CD62 and higher levels of aCL IgG were found compared to PAPS patients with normal platelet count. No correlation was found between activated platelets and both lupus anticoagulant antibodies and PalgG. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, thrombocytopenia and aPL levels.
Predictors of renal outcome in diffuse proliferative glomerulonephritis in systemic lupus erythematosus
Authors: Mosca M. , Pasquariello A. , Tavoni A. , Moriconi L. , Moneta I. , Innocenti M. , Bencivelli W. , Bombardieri S. 
Published: November 2007

The occurrence of nephritis is considered to be the most important factor influencing the prognosis in systemic lupus erythematosus (SLE). Despite the apparent histological similarity of the lesions, however, patients with diffuse proliferative glomerulonephritis (DPGN) may exhibit different outcomes. A retrospective study was carried out on 81 SLE patients with DPGN to evaluate the prognostic significance of different clinical, serological and histological variables; in particular, 95 renal biopsies were re-evaluated and the activity and chronicity indices for the patients were determined. A positive correlation was observed between the presence of chronic lesions on renal biopsy and a poor renal outcome (<0.001). Moreover, in the repeat biopsies the patients with a poor outcome showed a higher degree of chronic lesions. Active lesions and other clinical and serological parameters did not correlate with the outcome.
Prevalence of 13 autoantibodies and of the 16/6 and related pathogenic idiotypes in 465 patients with systemic lupus erythematosus and their relationship with disease activity
Authors: Villarreal GM , Drenkard C. , Villa AR , Slor H. , Shafrir S. , Bakimer R. , Shoenfeld Y. , Alarcón-Segovia D. 
Published: November 2007

With a cross sectional study of 465 consecutive systemic lupus erythematosus (SLE) patients tested for 13 autoantibodies (Aab) and two idiotypes we determined the prevalence of Aab according to disease activity, both general and at particular organ systems. Seventy seven percent of SLE sera had at least one Aab and 56% had it at high titres. Pathogenic idiotypes had a prevalence of less than 10% and 166 sera had Aab to 5 or more antigens and 9 sera had Aab against all 13 antigens tested. Patients with active disease had increased prevalence of Aab to DNP, ssDNA, ENA, mitochondria and histones when considered at 5 s.d. above the mean of normal controls. The higher positivity of Aab in patients with active disease was confirmed in logistic regression analysis adjusted by age, disease duration, and intensity of treatment. A trend was observed of increased prevalence and titres of Aab from inactive disease without treatment, to inactive disease but still being treated, to active disease. Only 22% of patients with active disease had no Aab and the higher the number of Aab the higher the frequency of active disease. Patients with active arthritis, and to a lesser degree those with active mucocutaneous involvement, had higher prevalence and titres of most autoantibodies than patients with disease activity at other organ systems. Active renal disease associated only with anti-dsDNA, whereas active CNS disease associated with anti-mitochondrial Aab. Our findings support the vision of SLE as an immune dysregulation leading to polyclonal B cell .. activation with resulting production of multiple Aab. Their profiles seem influenced by genetical, hormonal and environmental factors and, in turn, they contribute to the clinical picture in each patient. Disease activity influences the presence of some, but not all, Aab and some of them may remain present in some patients, even in remission.
Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—A meta-analysis
Authors: Wahl DG , Guillemin F. , de Maistre E. , Perret C. , Lecompte T. , Thibaut G. 
Published: November 2007

Objective: To describe the relative risk for venous thrombosis (VT) associated with antiphos pholipid antibodies (aPL) in systemic lupus erythematosus (SLE). Design: Systematic review and meta-analysis of 26 articles that examined the association between aPL and VT in SLE. Setting: Mostly secondary and tertiary referral centres. Patients: 2249 patients with SLE, 1120 tested for LA (lupus anticoagulant) and 1563 tested for aCL (anticardiolipin antibodies). Main outcome measures: A summary of study characteristics and a critical appraisal of study quality were done. Two statistical combinations of 18 primary studies that examined the association of VT and LA and of 14 studies that examined the association of VT and aCL were performed to estimate the risk for VT associated with aPL. Results: The odds ratios of the risk of VT related to the LA summarized from 18 studies were 5.61 [95% CI; 3.80-8.27] overall, 6.32 [CI; 3.71-10.78] for deep venous thrombosis and pulmonary embolism, 11.6 [3.65--36.91] for recurrent venous thrombosis after the first event. The odds ratios of the risk of VT related to aCL summarized from 14 studies were 2.17 [95% CI; 1.51-3.11] overall, 2.50 [CI; 1.51-4.14] for deep venous thrombosis and pulmonary embolism, 3.91 [1.14- 13.38] for recurrent venous thrombosis after the first event. Conclusions: Patients with SLE and LA are at approximately six times greater risk for VT than patients without LA, whereas patients with SLE and aCL are approximately two times greater risk for VT than patients without aCL. We have identified important methodologic limitations and differences in study characteristics. Other risk factors for VT have not been thoroughly evaluated in these studies. Further studies are needed that provide an accurate estimate of the absolute risk for aPL related VT.