bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of immunoblot profile of anti-SSA/Ro-SSB/La antibodies over time in mothers whose children have neonatal lupus
Authors: Tseng C-E. , Di Donato F. , Buyon JP
Published: November 2007

Neonatal lupus is strongly associated with antibodies reactive with SSA/Ro-SSB/La pro teins, independent of maternal disease activity or classification. We sought to determine whether the fine specificity of antibody profiles remains stable or evolves over time and whether these findings relate to clinical status. Sera from 23 mothers whose children had neonatal lupus (22 heart block, one skin) were evaluated by SDS-immunoblot. For each mother two samples were available at least 13 months apart; the mean duration of time between testing was 45 months ± 27 S.D. (range 13-108 months). Twenty-two of the 23 initial profiles were identical to the results obtained in a later sample. The health status of seven (30%) of 23 mothers changed after the birth of the affected infant but the immunoblot specificity of the antibodies remained unchanged. SLE was the initial and final diagnosis in the only mother whose profiles differed, with development of weak reactivity to 48 kD SSB/La in addition to the 52 kD SSA/Ro after 14 months. In conclusion, the fine specificity of anti-SSA/Ro-SSB/La antibodies as assessed by immunoblot is highly stable for years. Progression of clinical status was not associated with a concomitant change in antibody profile.
Autoantibodies to the collagen-like region of C1q are strongly associated with classical pathway-mediated hypocomplementemia in systemic lupus erythematosus
Authors: Frémeaux-Bacchi V. , Weiss L. , Demouchy C. , Blouin J. , Kazatchkine MD
Published: November 2007

We have investigated the presence of autoantibodies to the collagen-like region (CLR) of C1q and its relationship with classical pathway-dependent hypocomplementemia in patients with SLE. Antibodies to CLR/C1q were quantitated in the plasma of 113 unselected patients with SLE by ELISA, using purified CLR as antigen. Plasma concentration of C3, CH50 activity and C2 hemolytic activity were determined according to standard pro cedures. The prevalence of 1gG antibodies to CLR/C1q in the study population was 33.6%. Plasma titers of anti-CLR/C1q autoantibodies showed a strong negative correlation with CH50 activity ( p < 0.0001) and with plasma levels of C3 ( p < 0.0001). Eighty-five percent of patients with severe complement consumption exhibited high titers of anti-CLR/C1q anti bodies in plasma, independently of clinical disease activity. Anti-CLR/C1q antibodies were present in the plasma of 38% of patients with moderate classical pathway consumption and 14% of patients with no evidence of complement consumption. Analysis of sequential samples from six patients over a period of 18 to 24 months demonstrated that changes in CH50 activity mirrored those of the plasma titers of anti-CLR/C1q antibodies. Acquired hypocomplementemia through the classical pathway is strongly associated with the pres ence of anti-CLR/C1q autoantibodies in SLE. The results suggest that anti-CLR/C1q anti bodies may perpetuate classical pathway activation, independently of clinical disease activity.
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.
Lymph node cell vaccination against the lupus syndrome of MRL/lpr/lpr mice
Authors: Ben-Yehuda A. , Bar-Tana R. , Livoff A. , Ron N. , Cohen IR , Naparstek Y.
Published: November 2007

Immunization with pathogenic lymphoid cells has been shown to induce resistance to disease in experimental animal models of cell mediated autoimmunity. In the present work we tested the effectiveness of this approach in a spontaneous murine autoimmune disease, the MRL/lpr/lpr (MRL/1) murine lupus model. We now report that the anti-DNA anti bodies and glomerulonephritis of MRL/1 mice could be prevented by the adoptive transfer of spleen cells from MRL/+ mice that had been vaccinated with MRL/1 lymph node T lymphocytes, but not by direct vaccination of MRL/1 mice with their cells. These results indicate that the lupus of MRL/1 mice is susceptible to regulation by adoptive vaccination and that these autoimmune mice lack the ability to raise a suppressive response against their own pathogenic cells.
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.
Common variable immunodeficiency in a patient with systemic lupus erythematosus
Authors: Swaak Ajg , van den Brink HG
Published: November 2007

This report describes a young girl who developed systemic lupus erythematosus at the age of 11. In the years thereafter a conversion took place from hypergammaglobulinemia to hypogammaglobulinemia with the absence of circulating and bone marrow B-cells. Some aspects of the aetiopathogenesis of common variable immunodeficiency are discussed.
Post-partum dilated cardiomyopathy in anti-phospholipid positive woman
Authors: Airoldi ML , Eid O. , Tosetto C. , Meroni PL
Published: November 2007

Recurrent fetal loss and pregnancy complications, especially severe early-onset preeclamp sia, are frequently associated with anti-phospholipid antibodies. We report a case of post- partum cardiac involvement leading to dilated cardiomyopathy in a woman with a persistent positivity for anti-cardiolipin and anti-nuclear antibodies. Her clinical and obstetric record reported two previous fetal losses but no other signs characteristic of the anti-phospholipid syndrome or diagnostic for a systemic lupus erythematosus. Post-partum cardiomyopathy might be another cardiac presentation of the anti-phospholipid syndrome, in addition to the well known valvular involvement. In patients with persistent positivities for anti-phospholipid antibodies, a prompt identification of such a complication in the post- partum period should be taken into account by physicians. Adequate cardiologic treatment associated with antiaggregant and steroid therapy might be useful to prevent further com plications in these patients.
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.
Review : Elevated levels of anticardiolipin antibodies and epilepsy in lupus patients
Authors: Liou H-H. , Wang C-R. , Chen C-J. , Chen R-C. , Chuang C-Y. , Chiang I-P. , Tsai M-C.
Published: November 2007

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we inves tigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies ( P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.
Serum and urinary interleukin-6 in systemic lupus erythematosus
Authors: Peterson E. , Robertson AD , Emlen W.
Published: November 2007

Dysregulation of IL-6 production has been proposed as a pathogenic mechanism in SLE. We asked if serum or urine IL-6 levels could serve as indicators of systemic lupus erythematosus (SLE) disease activity. Using a sensitive enzyme-linked immunosorbent assay (ELISA), we measured serum and urine IL-6 in 56 SLE patients. Disease activity was assessed using a standard clinical index, the Systemic Lupus Activity Measure (SLAM). Only seven of 56 SLE patients had elevated serum IL-6 levels, compared with 1 of 32 controls (NS). SLE disease activity did not correlate with serum IL-6 levels. Sixteen of 50 SLE patients in whom urine IL-6 was measured exhibited elevated urine IL-6 levels, compared with 1 of 17 controls ( p = < 0.05). Urine IL-6 levels correlated with overall disease activity and with the presence of active urinary sediment. Our results indicate that serum IL-6 is not a predictor of disease activity in SLE, but that urine IL-6 may be a marker of active nephritis.
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.
Autoantibody profile in African-American patients with lupus nephritis
Authors: Garcia CO , Molina JF , Gutiérrez-Ureña S. , Scopelitis E. , Wilson WA , Gharavi AE , Espinoza LR
Published: November 2007

Lupus nephritis (LN) is one of the major risk factors for morbidity and overall mortality in systemic lupus erythematosus (SLE). Its pathogenesis is multifactorial, and a number of risk factors, including serological markers, have been identified in recent years, correlating with clinical course and disease severity. Furthermore, a distinctive autoantibody profile has recently been reported in African- American SLE women with LN. The aim of this study was to characterize the autoantibody profile in 222 African-American SLE patients, 94 with LN and 128 without. Only anti-dsDNA achieved statistical significance between the two groups (P < 0.05). Fourteen (14.9%) patients with LN and 15 (11.7%) without it exhibited positive anti-Ro/SS-A, anti-Sm, and anti-nRNP, but without anti-La/SS B (P > 0.6). We conclude that African-American SLE patients with LN do not exhibit a specific or distinctive autoantibody profile. However, our data confirm the value of anti-dsDNA in SLE patients with LN.
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.
Uncommon cutaneous manifestations of lupus erythematosus
Authors: Mascaro JM , Herrero C. , Hausmann G.
Published: November 2007

Cutaneous manifestations of lupus erythematosus (LE) are, usually, characteristic enough to permit an easy diagnosis. However, some patients may present less typical lesions, associated or not to the classic ones. Therefore, irrespectively of the variety of LE (acute, subacute and chronic), in absence of the typical butterfly rash, erythematosquamous papules or plaques, or any of the characteristic cutaneous alterations, it is important (even though not always easy) to recognize the uncommon and/or atypical changes of the skin.
Cutaneous lupus erythematosus during the neonatal and childhood periods
Authors: Lee LA , Weston WL
Published: November 2007

Cutaneous lupus erythematosus may be related to maternal autoantibody production in the neonatal lupus syndrome, or may occur later in childhood, with or without findings of systemic lupus erythematosus (SLE). In the first section, we will discuss the transient, passively transferred neonatal disease, and in the second, we will discuss the persistent, actively acquired forms of lupus erythematosus in childhood.
Phototesting and photoprotection in LE
Authors: Walchner M. , Messer G. , Kind P.
Published: November 2007

Photosensitivity and induction of skin lesions following UV radiation is a common problem of patients with cutaneous and systemic forms of lupus erythematosus. The detrimental effect of UV radiation to patients with lupus erythematosus was already recognized in the last century. Skin lesions can now be provoked under standardized conditions allowing the diagnosis and classification of patients with photosensitive disorders. The aim of this review is to give an overview on the history, test procedure and test results in patients with lupus erythematosus.
Ultraviolet light-induced keratinocyte apoptosis: A potential mechanism for the induction of skin lesions and autoantibody production in LE
Authors: Casciola-Rosen L. , Rosen A.
Published: November 2007

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.
Review: Behaviour of MRL Mice: An Animal Model of Disturbed Behaviour in Systemic Autoimmune Disease
Authors: Szechtman H. , Šakić B. , Denburg J.A.
Published: November 2007

Evidence is reviewed indicating that development of lupus-like disease in the MRL-1pr substrain of mice coincides with a change in behaviour, suggestive of altered emotional reactivity and cognitive performance. The altered behaviour, termed 'autoimmunity-associated behavioural syndrome', is related to abnormal autoantibody and cytokine production. Moreover, immunosuppressive treatment with cyclophosphamide prevents the appearance of some behavioural deficits. It is argued that the MRL strain of mice constitute an animal model of behavioural dysfunction in autoimmune disease, and can be used to investigate the mechanisms by which an insidious autoimmune/inflammatory process alters mood and behaviour and may result in some forms of mental disorders.
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.
Elevated serum levels of cyclo (His-Pro), an endogenous inhibitor of pituitary prolactin secretion, in systemic lupus erythematosus patients
Authors: Jara L.J. , Prasad C. , Espinoza L.R.
Published: November 2007

Cyclo (His-Pro) or CHP is a cyclic dipeptide that is known to elicit many biologic activities including inhibition of pituitary prolactin (PRL) secretion. PRL stimulates humoral and cell mediated immune responses and hyperprolactinemia has been found in a subset of systemic lupus erythematosus (SLE) patients in association with active disease. To explore whether CHP may play a role in SLE patients, we measured, CHP and PRL levels in sera of 21 SLE patients and 11 normal controls. The results of this study show significantly ( P < 0.001) high levels of CHP in SLE compared to controls. However, there was no significant correlation between serum PRL and CHP levels in SLE patients ( r = 0.027, P = 0.29). The increase in serum levels of CHP may be in an attempt to increase hypothalamic content of dopamine which in turn would decrease pituitary PRL synthesis in hyperprolactinemic SLE patients.
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.
Congenital heart block and subsequent connective tissue disorder in adolescence
Authors: Hubscher O. , Carrillo D. , Reichlin M.
Published: November 2007

A young girl born to a mother with systemic lupus erythematosus (SLE) had congenital heart block and developed symptoms of a connective tissue disorder at the age of 13 y. When first seen at the age of 15 y she was found to have an unclassified connective tissue disorder and to be seropositive for anti Ro/SSA and U1 RNP. This constellation of clinical/serological features has not been described among the reported handful of patients with congenital heart block and subsequent development of a connective tissue disorder.
Enhanced expression of nucleobindin in lymphatic organs of lupus-prone mice
Authors: Iizuka H. , Kubota T. , Satake F. , Hirokawa G. , Miura K. , Kurosawa Y. , Miyasaka N. , Kanai Y.
Published: November 2007

Nucleobindin (Nuc) was originally identified as a 55 kDa protein that enhanced anti-DNA antibody production in cultures of autoimmune MRL/ lpr mouse spleen cells. cDNA cloning and the production of recombinant protein (rNuc) have revealed that rNuc binds to DNA and Ca2+ by means of leucine zipper and EF-hand motif structures. In vitro and in vivo effects of rNuc to induce autoantibodies including anti-dsDNA antibody in normal mice have been demonstrated; however, whether Nuc is involved in the state of autoimmunity occurred in MRL/ lpr, C3H/ gld and male BXSB mice has not been elucidated. Here we report that the expression of Nuc mRNA is upregulated with age in the lymphatic organs and is positively correlated to the serum levels of Nuc in these lupus-prone strains of mice. Upon immunization with KLH in Freund's complete adjuvant, normal BALB/c mice also showed an elevated level of Nuc in their serum and elevated Nuc mRNA in their lymphatic organs. In addition, in vitro stimulation of BALB/c splenocytes with Con A or LPS remarkably enhanced Nuc mRNA expression. These results suggest that upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is related to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc in the induction or enhancement of autoimmunity in lupus models of mice.
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.
IgA deficiency and SLE: prevalence in a clinic population and a review of the literature
Authors: Rankin Ecc , Isenberg DA
Published: November 2007

An association between systemic lupus erythematosus (SLE) and immunoglobulin A (IgA) deficiency has been reported previously and may have therapeutic consequences for patients who require treatment with intravenous immunoglobulin. We report the prevalence of IgA deficiency in a clinic population of 96 patients with SLE. Five patients were found to be consistently IgA deficient. These patients were more likely to be West Indian, to have anti-Sm and anti-La antibodies and to have a speckled pattern of antinuclear antibody. There were no significant differences in clinical features between IgA deficient and other SLE patients, nor in SLE-related HLA alleles. We thus confirm the increased prevalence of IgA deficiency in patients with SLE. A review of the literature is presented and we speculate on the nature of the link between IgA deficiency and SLE.
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.
CD69 to CD3 ratio of peripheral blood mononuclear cells as a marker to monitor systemic lupus erythematosus disease activity
Authors: Su C-C. , Shau W-Y. , Wang C-R. , Chuang C-Y. , Chen C-Y.
Published: November 2007

CD69 is an early T cell activation marker. In order to investigate whether the disease activity of systemic lupus erythematosus (SLE) is correlated with T cell hyperactivity as well as B cell hyperactivity, we measured the CD69 to CD3 ratio (CD69/CD3) of peripheral blood mononuclear cells (PBMCs) from 42 SLE patients and 18 healthy controls. To assess B cell activation, we measured the levels of anti-dsDNA, complement C3 and C4. Disease activity was assessed with the SLE disease activity index (SLEDAI) score. The mean value (± standard deviation) of CD69/CD3 for SLE patients (3.34 ± 0.486) and healthy controls (0.92 ± 0.015) were significantly different (P < 0.05). CD69/CD3, anti-dsDNA, C3 and C4 were all significantly correlated with SLEDAI (r = 0.50, 0.51, -0.68, -0.31, respectively, P < 0.05). CD69/CD3 could explain 25.4% of the variance in SLEDAI, and 6.7% of the variance that was independent of anti-dsDNA, C3 and C4. In patients with SLEDAI scores which were discordant with anti-dsDNA, C3 and C4 values, CD69/ CD3 still showed high correlation with SLEDAI. We conclude that CD69/CD3, which detects T cell activation, is correlated with SLEDAI scores. Thus, T cell activation contributes part of the disease activity independent of B cell activity. This marker can complement in the estimation of disease activity when levels of anti-dsDNA, C3 and C4 fail to show good correlation.
Association between IgM anticardiolipin antibodies and deep venous thrombosis in patients without systemic lupus erythematosus
Authors: Oger E. , Leroyer C. , Dueymes M. , Le Moigne E. , Bressolette L. , Escoffre M. , Youinou P. , Mottier D.
Published: November 2007

Patients with systemic lupus erythematosus (SLE) are at risk of developing deep venous thrombosis (DVT). Should anticardiolipin antibodies (aCL) be detectable, this risk is significantly raised, particularly when these autoanti-bodies are cofactor-dependent. We conducted a cross-sectional study of consecutive unselected outpatients referred for clinical suspicion of DVT, as an attempt to address the following questions: firstly, were aCL antibodies associated with DVT in non-SLE patients? Secondly, was this association related to the cofactor dependence? From March 1992 to February 1994, 208 patients were enrolled in the study. Venography was positive in 110 patients (DVT patients), while the diagnosis of DVT could not be confirmed in the remaining 98 (referred to as disease controls). ACL was measured by ELISA, for IgG and IgM isotypes in two ways: fetal calf serum or bovine serum albumin were used as blocking agents to distinguish between cofactor- dependent and cofactor-independent antibodies. Positive aCL was defined as optical density (OD) values greater than the 95th percentile of OD distribution of 60 healthy controls. We found a high frequency of positive IgG aCL antibodies in both DVT patients and in disease controls (25.5 vs 23.5%). We suggest an association between IgM aCL and DVT. This association was, however, not dependent on the cofactor requirement.
C2 deficiency in blood donors and lupus patients: prevalence, clinical characteristics and HLA-associations in the Brazilian population
Authors: Araújo Mnt , Silva NP , Andrade Lec , Sato EI , Gerbase-DeLima M. , Leser PG
Published: November 2007

The objective of the present study was to investigate the prevalence, clinical characteristics, and HLA associations of C2 deficiency in the Brazilian population. The frequency of C2 deficiency profile (C2Q° profile) was 2.2% among 1503 blood donors and 6.6% among 166 patients with systemic lupus erythematosus (SLE). A higher incidence of clinical manifestations possibly related to immune complex disease was observed among blood donors with C2Q° profile and their relatives with C2Q° profile when compared to the normal C2 relatives. The comparison of clinical and laboratory features between SLE patients with C2Q° profile and those with normal C2 revealed earlier disease onset, higher frequency of oral ulcerations and lower frequency of anti-native DNA antibodies in the first group. The HLA study conducted on 18 individuals with C2Q° profile (11 blood donors and 7 SLE patients) confirmed the previously reported association with the antigens HLA-A25, B18 and DR2, supporting the concept that probably most C2 deficiency cases, throughout the world, are due to a single mutation in the C2 gene in linkage disequilibrium with the A25B 18DR2 haplotype.
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.
Review : Lack of linkage between anti-nuclear antibody or clinical features of systemic lupus erythematosus (SLE) and TCR-A/Vβ loci in families of subjects with SLE
Authors: Huang Q. , Morris D. , Dunckley H. , Grennan D. , Manolios N.
Published: November 2007

The role of the TCR-A and TCR-Vβ genes in the genetic predisposition to SLE expression and anti nuclear antibody (ANA) production were examined by linkage analysis in eighteen multiplex and forty-three simplex SLE families. All subjects were Caucasian. A significantly increased prevalence of positive ANAs in first-degree relatives of SLE patients from multiplex families was noticed compared to that of simplex families. Linkage between TCR-A/Vβ genes and SLE expression and ANA production were analysed by affected sib-pair method. Results showed that the haplotypes identical by descent sharing TCR-A and TCR-Vβ genes in the affected sib-pairs was not different from that expected (P = 0.93 and P = 0.74, respectively). There was no linkage between ANA positivity and TCR-A and TCR-Vβ genes in ANA positive sib-pairs from both multiplex and simplex families. This study suggests that germline TCR-A and TCR-Vβ gene loci confer no susceptibility to ANA and SLE expression.
Dyslipoproteinemias in systemic lupus erythematosus: influence of disease, activity, and anticardiolipin antibodies
Authors: Borba EF , Bonfá E.
Published: November 2007

Objective: To determine the influence of systemic lupus erythematosus (SLE), disease activity, and anticardiolipin antibodies (aCL) on lipid profile, in order to identify patients with high risk for coronary artery disease (CAD).

Methods: Fasting lipid profiles were performed in 36 consecutive female SLE patients without any therapy and 30 controls. Exclusion criteria were diabetes mellitus, CAD, liver or thyroid disease, ingestion of lipid-raising drugs, serum creatinine ≥ 1.5 mg/dl, and proteinuria ≥ 0.5 g/d. Disease activity was measured by SLEDAI.

Results: High levels of VLDL-C and TG and low levels of HDL-C, the 'lupus pattern', were observed in inactive SLE compared to controls (P < 0.05). Active disease enhanced this difference inducing a more striking increase in VLDL-C and TG levels and also a decrease in HDL-C and LDL-C levels compared to inactive SLE patients (P < 0.05), characterizing the 'active lupus pattern'. Moreover, a significant correlation was found between SLEDAI scores and all lipid fractions. Furthermore these lipid abnormalities were particularly associated with vasculitis. Lower HDL-C levels detected in IgG aCL+ patients compared to IgG aCL - patients were not confirmed by two-way analysis of variance which demonstrated that this difference was exclusively caused by disease activity.

Conclusions: Our findings suggest that SLE patients have a lipid profile abnormality which is aggravated by disease activity and may reside in a defect of VLDL metabolism. This pattern of dyslipoproteinemia may increase the risk of developing coronary artery disease.