bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased mRNA Levels Coding for Poly(ADP-Ribose) Polymerase in Lymphocytes of Patients with SLE
Authors: Lee Jeremy S. , Haug Brenda L. , Sibley John T.
Published: November 2007

Poly(ADP-ribose) metabolism is altered in patients with SLE. In order to localize the defect, the levels of poly(ADP-ribose) polymerase-specific mRNA were measured from dot blots of total RNA from peripheral blood lymphocytes. In this preliminary study, eleven patients with SLE and two with antiphospholipid syndrome were compared to three controls. It was found that the mean levels of specific mRNA were ten fold lower in the PBL from SLE patients compared to controls and no overlap of values was seen between the two groups. No such decrease was seen in the PBL from the patients with antiphospholipid syndrome. It is concluded that the defect in poly(ADP-riboseO polymerase metabolism that is seen in SLE patients occurs at the level of transcription or mRNA turnover.
Evidence for Intrathecal Synthesis of Autoantibodies in Systemic Lupus Erythematosus with Neurological Involvement
Authors: Mevorach Dror , Raz Eyal , Steiner Israel
Published: November 2007

The diagnosis of systemic lupus erythematosus (SLE) in a patient who presents with isolated central nervous system (CNS) abnormalities, is a difficult clinical challenge. The pathogenesis of such CNS involvement in SLE is unknown. Twelve patients with active SLE were examined for serum and cerebrospinal fluid (CSF) autoantibodies and compared with 21 patients with headache. Four of six patients with SLE and active CNS presentation had CSF autoantibodies while none of the other SLE patients and the controls had autoantibodies. We describe these four patients in whom immunological work-up revealed CSF antinuclear, anti-DNA, anti-SSA/Ro, anti-SSB/La and antineuronal autoantibodies. A newly devised antibody activity index provided means to demonstrate that the CSF autoantibodies in these patients were produced intrathecally. Beyond the importance of our finding of the potential role of autoantibodies in the pathogenesis of CNS damage in SLE, we propose that CSF analysis for autoantibodies should become an essential part of the diagnostic work-up in autoimmune diseases with CNS involvement.
Massive Cerebral Calcification in Systemic Lupus Erythematosus: an Report of an Unusual Case
Authors: Garcia Raya Pilar , Gil Aguado Antonio , Merlo Ma José Simon , Lavilla Uriol Paz , Astudillo Aurelio Vega , Garcia Puig Juan
Published: November 2007

A 38-year-old woman with systemic lupus erythematosus (SLE) and an acute neurological event was studied with computed tomography (CT) and magnetic resonance (MR). Marked intracranial calcification mimicking that seen in hypoparathyroid states was found. The clinical significance of this finding is not clear and the mechanism for cerebral calcification remains unknown.
Pregnancy in Systemic Lupus Erythematosus: a Prospective Study
Authors: Derksen Ronald H.W.M. , Bruinse Hein W. , de Groot Philip G. , Kater Louis
Published: November 2007

The objective of this work was to analyse the course of maternal disease and fetal outcome in pregnant patients with systemic lupus erythematosus (SLE) counselled and followed according to a protocol intended to optimize maternal and fetal outcome. The prospective study included all pregnancies between 1987 and 1993 in SLE patients known at least 6 months before pregnancy at the Lupus Clinic of our hospital. In 25 patients there were 35 pregnancies. Thirty-four (97%) started at sustained remission of disease; 11 (31%) were in women with antiphospholipid antibodies (aPL); 14 (40%) in women with a history of biopsy-proven lupus nephritis; one (3% in a woman with a serum creatinine above 125 μmol/l. In 29 pregnancies (82%) maternal disease remained inactive during gestation. In three pregnancies (9%) active disease was treated with prednisone. There were no serious post-partum flares of disease. Pregnancy resulted in 25 (71%) live births, 8 (23%) first trimester abortions, and one intrauterine fetal death. One pregnancy was terminated because of hydrocephalus. Nine of 25 (36%) live births were delivered by caesarean section. For 6 of 9 (67%) caesarean sections the indication was fetal distress and pre-eclampsia.

In the majority of patients with SLE who conceive at remission, the disease does not flare in pregnancy. With optimal obstetric care, close follow-up and treatment with low-dose aspirin if aPL are present, a high success rate (71%) can be achieved.
Acute Sideroblastic Anemia in Active Systemic Lupus Erythematosus
Authors: Javier Jiménez-Balderas F. , Morales-Polanco Manuel R. , Gutierrez Laura
Published: November 2007

This work describes the development of sideroblastic anemia (SA) during the clinical activity of systemic lupus erythematosus (SLE) in two patients. The cases refer to two women with SLE who developed SA during a relapse of the illness. Both patients fulfilled at least four criteria of the American Association of Rheumatology for SLE. In one patient, the treatment with prednisone was followed by the resolution of the SLE activity and the disappearance of the SA. Several years later there was no evidence of ringed sideroblasts or malignancy in the bone marrow. In the other patient, the clinical activity of the SLE and SA developed during the beginning of a septicemic event which finally led to her death.

Our clinical cases allow us to show that the transitory development of SA can occur during a period of clinical activity of SLE and that its association, although infrequent, is due to a common physiopathogenic mechanism.
New Environmental Agents Associated With Lupus-Like Disorders
Authors: Love Lori A.
Published: November 2007

An increasing number of environmental agents are being investigated as possible risk factors in the etiology of certain connective tissue disorders. Exposure to a variety of therapeutic agents, foods and dietary supplements, occupational and other toxic exposures, and infectious agents has been associated with the onset of lupus-like disorders. The mechanisms by which these agents might induce lupus remain unknown but may involve alteration of cellular components or activation of the immune system. Individual host susceptibility factors, including pre-existing organ dysfunction and particular metabolic enzyme or immunogenetic phenotypes, may also be important risk factors for development of environmentally-associated lupus-like disorders. Awareness of the many environmental agents implicated with lupus and related disorders, and dissection of their pathogenetic mechanisms through appropriate case-controlled investigations, may identify additional toxic agents and may lead to a better understanding of the idiopathic lupus syndromes.
Serum soluble markers of immune activation and disease activity in systemic lupus erythematosus
Authors: Samsonov Mikhail Y , Tilz Gernot P , Egorova Olga , Reibnegger Gilbert , Balabanova Rimma M , Nassonov Eugeney L , Nassonova Valentina A , Wachter Helmut , Fuchs Dietmar
Published: November 2007

We investigated a possible association between markers of immune activation and disease activity in 52 patients with systemic lupus erythematosus (SLE). Serum concentrations of neopterin, beta- 2-microglobulin, 55 kD-type soluble tumor necrosis factor receptor, soluble interleukin-2 receptor and soluble CD8 were compared to the Index of European Consensus Lupus Activity Measurement (ECLAM). All markers of immune activation, except sCD8, significantly correlated with ECLAM. Stepwise multiple linear regression analysis revealed erythrocyte sedimentation rate and neopterin to correlate best with ECLAM (multiple correlation coefficient = 0.74, P < 0.001). The study shows that serum neopterin concentrations are a useful independent index for disease activity in SLE. The finding of enhanced concentrations of various parameters of immune activation in patients confirm a role of the T cell and macrophage activation in the pathogenesis of SLE.
Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjögren's syndrome
Authors: Satoh Minoru , Yamagata Hajime , Watanabe Fumie , Nakayama Shoji , Ogasawara Takashi , Tojo Takeshi , Akizuki Masashi
Published: November 2007

A 69-year-old Japanese women who had been followed up for 10 years as a primary Sjögren's syndrome, is reported. She suddenly developed serological and clinical characteristics of systemic lupus erythematosus (SLE): anti-Sm and anti-dsDNA antibodies followed by nephrotic syndrome and pancytopenia. This case suggests that the diagnosis of primary Sjögren's syndrome should be considered as tentative in certain cases and that the development of serological characteristics precede and are associated with the development of clinical symptoms of SLE.
Dissecting aortic aneurysm in systemic lupus erythematosus
Authors: Sclair Miri , Nassar Hashem , Bar-Ziv Yaakov , Putterman Chaim
Published: November 2007

Many cardiovascular manifestations have been described in systemic lupus erythematosus (SLE). Aortic involvement, however, is very rare. We describe a 30-year-old woman with SLE who presented with extensive aortic dissection, and review the few reported cases. We discuss possible pathogenic mechanisms for aortic involvement in lupus and the appropriate diagnostic work-up.
Review : Serological markers of disease activity in systemic lupus erythematosus
Authors: Spronk Peter E , Limburg Pieter C , Kallenberg Cees GM
Published: November 2007

When measured serially by Farr assay at a frequency of approximately once a month, changes in levels of anti-dsDNA appear to be a good predictor of clinical disease activity. Although the role of antibodies to the RNA component of snRNP awaits further studies, measurement of anti-UsnRNP antibody levels seems to be of limited value in monitoring lupus patients in clinical practice. The same holds for antibodies to SSA (Ro) and anti-histone antibodies. More recently described antibodies to C1q are probably useful in the follow-up of SLE patients suspected of proliferative renal involvement. The best alternative to measuring levels of the antibodies mentioned before is probably serial analysis of activation of the complement cascade. Levels of complement factors like C3, C4 and, functionally, CH50 remain a useful parameter for monitoring disease activity in SLE, although fluctuations in anti-dsDNA as measured by Farr assay seem superior with respect to sensitivity and specificity for an ensuing relapse. Despite the problems in sampling, measuring levels of activated split products of complement factors like C3a, C3d or C5a may prove to be a valuable tool in the follow-up of lupus patients. The involvement of the endothelial surface is illustrated by rising sVCAM-1 levels prior to relapses in SLE. Although one could expect that subsequent inflammation should be reflected by increased levels of inflammatory molecules like CRP and IL-6, the use of these molecules as predictors of lupus activity seems limited. Interferon-α as a direct reflector of the effector phase seems, however, rather promising in this respect and awaits longitudinal studies to analyse the possible relation with clinical disease activity and other serological parameters.
New York University/Hospital for Joint Diseases experience with intravenous cyclophosphamide treatment: efficacy in steroid unresponsive lupus nephritis
Authors: Belmont H Michael , Storch Marc , Buyon Jill , Abramson Steven
Published: November 2007

The medical records of patients receiving cyclophosphamide for lupus nephritis between 1987 and 1993 at the New York University/Hospital for Joint Diseases Lupus Study Group Institutions were retrospectively reviewed. We identified 45 patients (38 female, seven male) who received a mean of 9 ± 1 (range 2-23) pulses of intravenous cyclophosphamide for diffuse proliferative glomerulone phritis ( n = 28), focal proliferative glomerulonephritis ( n = 7), membranous nephropathy ( n = 5), mesangial nephropathy with sclerosis (n = 1) or nephritis without biopsy (n = 4). Forty-two of the 45 patients received cyclophosphamide after failing steroid therapy. During a follow-up period of 52 ± 3 months, nine patients progressed to end-stage renal disease (ESRD) with three additional patients experiencing a doubling of the creatinine and two patients persistent nephrotic range proteinuria. There were no deaths directly attributable to cyclophosphamide and no patients developed hemorrhagic cystitis or malignancy. Ten of 37 women had ceased menstruating prior to cyclophosphamide therapy. Treatment-associated amenorrhea occurred in only three patients all over 27 years of age. Intermittent intravenous cyclophosphamide therapy of lupus nephritis is well tolerated and usually effective in maintaining renal function in patients unresponsive to steroids although, in our experience, 20% of patients developed ESRD and a total of 14 of 45 (30%) patients had unsatisfactory outcomes.
Ischemic optic neuropathy and high-level anticardiolipin antibodies in primary Sjögren's syndrome
Authors: Rosler Daniel H , Conway Mandi D , Anaya Juan-Manuel , Molina Jose F , Carr Ronald F , Gharavi Azzudin E , Wilson Wendell A
Published: November 2007

A 39-year-old woman with recurrent severe anterior ischemic optic neuropathy in the setting of Sjögren's syndrome was found to have high-titer IgM anticardiolipin antibodies (aCL) that were enhanced by the phospholipid-binding glycoprotein β2GP1. The recognition of IgM aCL-associated vasculopathy as a possible etiologic factor in the optic neuropathy in Sjögren's syndrome may be relevant in deciding appropriate therapy.
Factors associated with chronic renal failure in 121 patients with diffuse proliferative lupus nephritis: a case-control study
Authors: Arce-Salinas C.A. , Villa A.R. , Martínez-Rueda J.O. , Muñoz L. , Cardiel M.H. , Alcocer-Varela J. , Alarcón-Segovia D.
Published: November 2007

Lupus nephritis remains an important problem in patients with systemic lupus erythematosus (SLE). Some patients with diffuse proliferative lupus nephritis (DPLN) develop chronic renal failure (CRF). A case-control study was designed to determine the variables associated with CRF in patients with DPLN. We studied 121 patients with biopsy-proven DPLN seen in our institution from 1970 to 1988. There were 34 patients who developed CRF, the remaining were their controls. Clinical charts were reviewed and a pathologist re-scored blindly both activity and chronicity indices. The mean of age at SLE onset was 24.1 ± 7.9 years; the mean disease duration was 9.2 ± 6.1 years for controls and 6.1 ± 5 years for patients. The main variables associated with CRF were male sex, HR (hazard ratio): 12.6 (95% CI 1.6-98.2); activity index, HR 2.59 (1.07-6.3) ; severe infections, HR 2.9 (1.2-7.3); number of antihypertensive drugs, HR 2.5 (1.4-4.7); cellular crescents, HR 1.6 (1.2-2); and interstitial inflammation, HR 2.7 (1.5-5.1). A protective effect was observed with longer use of ≤20 mg of prednisone, HR 0.53 (95% CI 0.34-0.8); azathioprine, HR 0.6 (0.4-0.8); and length of formal education, HR 0.3 (0.09-0.94). Our results indicate that maleness, activity index, extracapillary proliferation and interstitial inflammation, as well as hypertension and severe infections associate with CRF in patients with DPLN, and treatment and higher education, perhaps through better therapeutic compliance, may be protective.
IgA-alpha-1-antitrypsin complex in systemic lupus erythematosus: preliminary report
Authors: Lacki J.K. , Schochat T. , Leszczynski P. , Mackiewicz S.H. , Muller W.
Published: November 2007

To investigate the role of the complex IgA-alpha-1-antitrypsin (IgA-AT) in systemic lupus erythematosus (SLE) and in mixed connective tissue disease (MCTD), and its possible relations to either activity of the disease or a treatment, we examined a concentration of IgA-AT complex in 65 SLE and 9 MCTD sera. Complex IgA-AT was evaluated using a double antibody enzyme-linked immunoassay (ELISA).

Twenty nine patients with SLE (44.6%) and three patients with MCTD (33.3%) had increased serum IgA-AT levels. The mean values of IgA-AT complex in patients with SLE and MCTD were higher than in healthy controls. Among the SLE group, patients with current neurological manifestation were characterized by an increase in IgA-AT serum concentration (2.45 ± 2.07 U vs. 0.78 ± 0.70 U, P < 0.001).

No relation was found between this complex and ESR level, C-reactive protein (CRP) concentration, or hemoglobin level. Ten SLE patients were treated with CTX intravenously. In this group of patients, IgA-AT complex level was found to be increased compared with patients without such a treatment (1.82 ± 1.30 U vs. 0.80 ± 0.67 U, P <0.05).

The present study provides two new observations. Firstly, IgA-AT complex is increased in SLE and MCTD compared with healthy controls, and secondly, patients with CNS involvement displayed a striking increased IgA-AT level.
Research methods for investigating causal relations between SLE disease variables and psychiatric symptomatology
Authors: Iverson G.L. , Anderson K.W. , McCracken L.M.
Published: November 2007

People with systemic lupus erythematosus (SLE) frequently experience psychiatric problems. Some researchers and clinicians presume that these psychiatric problems are a direct manifestation of the disease, while others suggest that psychosocial and environmental factors have greater etiological significance. The majority of the studies addressing these issues in patients with SLE are too methodologically limited to make confident conclusions regarding etiology. More methodologically sound research in this area is needed. This article describes some of the limitations in past research in the areas of sampling, measurement, research design, data analyses and data presentation. Suggestions for improved methodology in future research are offered.
Ontogeny of membrane cofactor protein: phenotypic divergence in the fetal heart
Authors: Gorelick A. , Oglesby T. , Rashbaum W. , Atkinson J. , Buyon J.P.
Published: November 2007

Human adult cells are protected from complement-induced damage in part by membrane cofactor protein (MCP, CD46). To examine fetal characteristics which might influence autoantibody-mediated diseases acquired in utero, such as heart block in neonatal lupus, the tissue expression of MCP was studied. Using a high ratio of acrylamide:bisacrylamide, immunoblots of tissues from six fetuses (aged 19-24 weeks) probed with rabbit anti-MCP antibodies revealed a band at 60 KD in addition to the known 65 KD and 55 KD isoforms which comprise the codominant allelic system of MCP. Five fetuses expressed the most common MCP polymorphism (predominance of the 65 KD isoform, upper band α-phenotype) in the kidney, spleen, liver and lung. In contrast, all hearts from these five fetuses demonstrated a different pattern in which there was a marked decrease in the intensity of the 65 KD band and accentuation of the lower molecular weight bands. In a sixth fetus, which expressed the second most common polymorphism (equal expression of the 65 KD and 55 KD MCP isoforms, αβ-phenotype), the heart was similar to the other tissues. These studies confirm the expression of MCP in early gestational life. Preferential expression of the MCP β-isoform in the majority of fetal hearts irrespective of the phenotype of other organs, suggests tissue-specific RNA splicing or post-translational modification which may relate to autoantibody-mediated injury in diseases such as neonatal lupus.
Cerebellar atrophy in systemic lupus erythematosus
Authors: Al-Arfaj HF , Naddaf HO
Published: November 2007

Central nervous system involvement in systemic lupus erythematosus (SLE) is common; this is especially so in patients with positive antiphospholipid antibody. However, cerebellar involvement is very unusual. In our institution, we have seen 150 cases of SLE over the last 10 years; however, this is the only patient who has cerebellar involvement due to SLE. The patient had no other neurological deficit, and no other cause apart from her SLE to explain her cerebellar ataxia. Her antiphospholipid antibody was negative.

The patient showed some improvement on high-dose steroids and azathioprin.
When does amyloidosis complicate systemic lupus erythematosus?
Authors: Orellana C. , Collado A. , Hernandez MV , Font J. , Del Olmo JA , Muñoz-Gomez J.
Published: November 2007

Secondary amyloidosis is a well recognised complication of rheumatic diseases, but the association with systemic lupus erythematosus is very unusual. We report the case of a patient with systemic lupus erythematosus who developed proteinuria due to renal amyloidosis. We also review the cases previously reported and the hypothesis on the pathogenic mechanisms.
Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in the USA
Authors: Hochberg M.C. , Perlmutter D.L. , Medsger T.A. , Steen V. , Weisman M.H. , White B. , Wigley F.M.
Published: November 2007

The objective of this study was to estimate the prevalence of self-reported physician-diagnosed systemic lupus erythematosus (SLE) in the USA. During the conduct of an epidemiologic study of systemic sclerosis (scleroderma), 16607 randomly selected telephone numbers in the continental USA were called to recruit controls. All potentially eligible women were asked 'Have you ever been told by a doctor that you have lupus or SLE'? Of 4034 women aged 18 and above who completed telephone screening, 15 stated they had a physician diagnosis of SLE, corresponding to a prevalence of 372 cases per 100000 (95% confidence intervals: 208, 614). After review of available medical records in six cases, however, the prevalence of 'validated' SLE was revised to 124 cases per 100000 (95% confidence intervals: 40, 289). , In conclusion, these data suggest that the prevalence of SLE in the USA may be up to three to 10-fold greater than previously estimated. Based on 1990 census data, we would project that over 275 000 women aged 18 and above have SLE in the USA.
Clinical significance of phospholipid-dependent anti-β2-glycoprotein I (β2-GPI) antibodies in systemic lupus erythematosus
Authors: Kaburaki J. , Kuwana M. , Yamamoto M. , Kawai S. , Matsuura E. , Ikeda Y.
Published: November 2007

We investigated the clinical significance of IgG phospholipid-dependent anti-β2-glycoprotein I (β2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-β2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-β2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-β2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-β2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-β2-GPI antibodies show an unique form of SLE.
Anticardiolipin antibodies in two elderly subpopulations
Authors: Juby A. , Davis P. , Genge T. , McElhaney J.
Published: November 2007

Previous studies have reported that the prevalence of certain autoantibodies is nonspecifically elevated in elderly subjects due to immunoscenescence. This study was undertaken to assess the prevalence of anticardiolipin antibodies (aCL) in two elderly subpopulations: Two hundred and eighteen elderly were included in this study; 63 healthy elderly had a prevalence of anticardiolipin antibodies of zero; 155 unselected frail elderly were prospectively evaluated and the prevalence of anticardiolipin antibodies in this group was found to be significantly increased at 18.7%. Subdivision of this group into those elderly clinically assessed as suffering from dementia showed a prevalence of 26.5% and stroke a prevalence of 31.6%. Both were found to be statistically significantly increased when compared with both the healthy and frail elderly population. Subdivision of the dementia patients into those suffering from multi-infarct type dementia (MID) and those suffering from Alzheimer's type dementia (AD) showed an association of 44% and 20%, respectively. The association of MID with aCL was significant. This study demonstrates therefore that anticardiolipin antibodies are not nonspecifically elevated in elderly subjects but are significantly elevated in elderly subjects with strokes and multiple infarct dementia.
Heart rate variability in patients with systemic lupus erythematosus
Authors: Stein KS , McFarlane IC , Goldberg N. , Ginzler EM
Published: November 2007

As patients with systemic lupus erythematosus (SLE) survive their episodes of disease activ ity, increasing morbidity is shown to be related to chronic cardiovascular complications. The objective of this study was to assess the cardiac parasympathetic autonomic functional status, as reflected by heart rate variability, in SLE patients with and without corticosteroid treatment. A cross-sectional study of SLE patients attending the Arthritis Clinic was done, using age and gender-matched controls. Thirty-four female patients, age 39 ± 11, were entered, 20 of whom were receiving steroids at the time of study. Time and frequency domain heart rate variability indices were significantly reduced in the SLE groups with and without corticosteroid therapy, as compared to controls. The indices were not, however, significantly different in the two SLE groups.
Mononeuritis multiplex in systemic lupus erythematosus: response to pulse intravenous cyclophosphamide
Authors: Martinez-Taboada VM , Blanco Alonso R. , Armona J. , Femandez-Sueiro JL , Gonzalez Vela C. , Rodriguez-Valverde V.
Published: November 2007

Severe mononeuritis multiplex in systemic lupus erythematosus (SLE) is quite rare and almost always accompanied by evidence of active disease in other organs, although occasionally it may be the presenting feature of the disease. We describe here two patients with SLE who presented a severe mononeuritis multiplex secondary to a necrotizing vasculitis which responded successfully to therapy with intravenous cyclophosphamide, and review the literature of similar cases.
Establishment and characterization of permanent human endothelial cell clones
Authors: Le Tonquèze M. , Jamin C. , Böhme M. , Le Corre R. , Dueymes M. , Youinou P.
Published: November 2007

Though vasculitic diseases have been claimed to be associated with anti-endothelial cells antibodies (AECA), there is a widespread awareness of the limitations of the tests currently in use. Our objective was therefore to establish clones, in the hope that some of them would express disease-specific membrane autoantigens. Two EC lines and 7 clones were estab lished by fusing human umbilical vein EC with epithelial A549/8 cells, and cloning by limit ing dilution. An additional clone was derived from the EA.hy 926 cell line. All clones carried EC markers, such as thrombomoduline (TM) and platelet-EC adhesion molecule 1 but differed from each other, depending on whether they expressed HLA class II antigen, LFA-1, thrombospondin receptor or von Willebrand factor (vWf) antigen. Clones were also characterized by their ability to release tissue plasminogen activator, interleukin 6, TM and vWf. This panel is meant to distinguish reactivities of AECA.
Immunology of antiphospholipid antibodies and their interaction with plasma proteins
Authors: Kandiah DA , Krilis SA
Published: November 2007

'Antiphospholipid' (aPL) antibodies are of clinical importance because of their strong association with vascular thrombosis, recurrent pregnancy loss, thrombocytopenia and other clinical manifestations like livedo reticularis, chorea and cardiac valvular disease1. While aPL antibodies have traditionally been thought to be directed against negatively- charged (anionic) phospholipids, current evidence suggests that these autoantibodies recog nise protein-phospholipid complexes or the proteins themselves2-4. A number of candidate proteins have been investigated with the two most extensively researched being β2 glycoprotein I and prothrombin.
Pharmacological intervention in antibody mediated disease
Authors: Coutts SM , Plunkett ML , Iverson GM , Barstad PA , Berner CM
Published: November 2007

The use of single signal anergy to inactive pathological B cells in an antigen-specific manner is discussed. Cross-linking surface immunoglobulin, with a construct which contains oligo valent B cell epitopes on a non-immunogenic molecular framework can be used to inac tivate the target B cells if the construct lacks T cells epitopes. An example of such a B cell toleragen is LJP 394, which inactivates anti-dsDNA-specific B cells in vivo in murine immu nized and spontaneous disease models. The drug enhances survival and lowers renal pathol ogy in BXSB mice. Appropriate definition of epitopes of pathological (auto) antibodies thus offers an opportunity for pharmacological intervention.
Neurological and obstetric manifestations of the antiphospholipid syndrome
Authors: Gatenby PA
Published: November 2007

The experience of a single centre with the neurological and obstetric complications of the antiphospholipid syndrome is presented and reviewed briefly with the general world liter ature. Both the neurologic and the obstetric manifestations exemplify the need for a greater understanding of underlying pathogenetic mechanisms and a more rigorous approach to therapy.
Libman-Sacks endocarditis in the antiphospholipid syndrome: immunopathologic findings in deformed heart valves
Authors: Ziporen L. , Goldberg I. , Arad M. , Hojnik M. , Ordi-Ros J. , Afek A. , Blank M. , Sandbank Y. , Vilardell-Tarres M. , de Torres I. , Weinberger A. , Asherson RA , Kopolovic Y. , Shoenfeld Y.
Published: November 2007

Objective. To examine the potential immunologic mechanism and involvement of antiphos pholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphos pholipid syndrome (APS).

Methods. Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immuno globulins, complement components, serum albumin and a monoclonal anti-idiotypic anti body to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls.

Results. Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS.

Conclusion. Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.
Review : Ultraviolet-A1 (340-400 nm) irradiation therapy in systemic lupus erythematosus
Authors: McGrath H. , Martínez-Osuna P. , Lee FA
Published: November 2007

Ultraviolet-A1 (UV-A1) wavelengths have been found effective in mitigating signs and symp toms of disease activity in systemic lupus erythematosus (SLE) but studies have been uncon trolled. To rigorously assess the effectiveness and safety of daily low-dose UV-A1 irradiation as a therapeutic agent in this disorder we enrolled 26 women with SLE in an 18-week two-phase study. During the initial six-week prospective, double-blind, placebo-controlled phase, the patients were divided into two groups; Group A was exposed to 60 kJ/m 2 of UV-A1 (340-400 nm) irradiation within a sunbed five days a week for three weeks and Group B was exposed for an equal amount of time to visible light of greater than > 430 nm (placebo). Each group was then crossed over for exposure to the other source for three weeks. During the second phase - 12 weeks - patients and physicians were unblinded and patients were irradiated with progressively decreasing levels of UV-A1 only.

Twenty-five patients completed the six-week placebo-controlled phase of the study and eighteen patients participated for the entire 18 weeks. In Group A the systemic lupus activ ity measure (SLAM) score improved significantly after three weeks of five-day-a-week UV-A1 irradiation (P < 0.05), regressing to baseline during the three weeks of placebo irra diation. Improvement recurred and progressed with six weeks of three-day-a-week UV-A1 irradiation (P < 0.05). Group B patients responded negligibly to the three weeks of visible light, more sharply to UV-A1, and as with Group A, maximally to the six weeks of three- day-a-week UV-A1 (P < 0.01). With twice- and then once-weekly UV-A1 irradiation the SLAM scores worsened slightly.

All patients decreased their drug use. Anti-double-stranded DNA antibodies (anti- dsDNA) decreased significantly (P < 0.05) and anti-nuclear antibodies non-significantly. Side effects were negligible. Visible light had no significant effect. In conclusion, low-dose UV-A1 irradiation effectively, comfortably, and without apparent toxicity diminished signs and symptoms of disease activity in SLE.
Review : A clinical and serological comparison of familial and non-familial systemic lupus erythematosus in Ireland
Authors: Gourley Ian S , Cunnane G. , Bresnihan B. , FitzGerald O. , Bell Aubrey L
Published: November 2007

Seventeen families, in which the diagnosis of SLE could be verified in two relatives, were included in the study. The diagnosis was made according to the revised 1982 ARA criteria. We compared the 34 cases of familial SLE in these 17 families with 34 non-familial SLE controls matched for age, sex, ethnicity and duration of disease. Comparisons were made for the presence of 26 clinical and 11 serological features. The frequency of clinical features was similar between the groups. The frequency of anti-Ro antibody was higher in the non-familial group (15 out of 34 compared to 6 out of 34, P = 0.036, McNemar's test), although this was not significant after application of Bonferoni's correction for the number of comparisons. No cases of familial IgA or familial complement deficiency were identified. It was noted that 10 of the 34 non-familial patients and only one of the familial patients had the combination of anti-Ro antibody and photosensitivity. The findings of this study support the hypothesis that familial SLE and non-familial SLE are the same clinical entity, although there are differences in the subtypes of disease.
Superior sagittal sinus thrombosis in a patient with systemic lupus erythematosus
Authors: Flusser D. , Abu-Shakra M. , Baumgarten-Kleiner A. , Flusser G. , Sukenik S.
Published: November 2007

Cerebral venous thrombosis is a rare cause of focal neurological damage in patients with SLE. We describe a patient with SLE who presented with a focal neurological deficit and subsequently developed increased intracranial pressure. A superior sagittal sinus thrombosis was diagnosed by MRI. The association between SLE and superior sagittal sinus throm bosis is discussed. Early diagnosis is essential because treatment leads to a positive clinical outcome.
Antiphospholipid antibody associated thrombosis: A consensus for treatment?
Authors: McCrae KR
Published: November 2007

The results of several studies have demonstrated that antiphospholipid antibodies (APLA) are associated with an increased risk of both venous and arterial thrombosis. Additional work has suggested that patients with antiphospholipid antibody-associated thrombosis are at a markedly increased risk for recurrent thrombotic disease, and several investigators have suggested that such patients should receive high-intensity anticoagulant therapy for an indefinite period of time for prophylaxis of recurrent thrombotic events. However, the majority of these studies are retrospective and include highly-selected patient populations, and the potential morbidity of long-term, intensive warfarin therapy has not been fully considered. In this article, studies concerning the incidence and prevention of recurrent thrombosis in patients with antiphospholipid antibodies are reviewed. I will also present the results of a survey in which opinions concerning selected issues in prophylactic anticoagulant therapy of patients with antiphospholipid antibody-associated venous thrombosis were obtained from prominent clinicians with expertise in this area. The results of the survey demonstrate that opinions concerning this issue vary widely, and emphasize the need for additional prospective studies examining the utility of specific anticoagulant regimens in the prophylaxis of recurrent thromboembolism in patients with antiphospholipid antibodies.
Induction of anticardiolipin antibody and/or lupus anticoagulant in rabbits by immunization with lipoteichoic acid, lipopolysaccharide and lipid A
Authors: Gotoh M. , Matsuda J.
Published: November 2007

It still remains unclear how anti-phospholipid antibody develops in a specific patient group, however, it is possible that certain microorganism(s) may cause anti-cardiolipin antibody (aCL) development since aCL is frequently detected in patients with Treponema pallidum (TP) and/or other infectious diseases. Accordingly, we conducted an investigation to clarify whether or not anticardiolipin antibody (aCL) and/or lupus anticoagulant (LA) can be induced in rabbits by immunization with Gram-positive or -negative microorganism derivatives, such as lipoteichoic acid, lipopolysaccharide and lipid A. We detected the induction of SLE type-aCL (β2GPI-dependent) and LA in some rabbits immunized with lipid A and lipoteichoic acid, thereby suggesting that some microorganisms may contribute to even the production of pathogenic (SLE-type) antiphospholipid antibody.
Bone mineral density and hormonal status in men with systemic lupus erythematosus
Authors: Formiga F. , Nolla JM , Mitjavila F. , Bonnin R. , Navarro MA , Moga I.
Published: November 2007

A loss in bone mass was reported in premenopausal systemic lupus erythematosus (SLE) women, but this problem has not been studied in SLE males. We evaluated bone mineral density (BMD) in SLE males and the relationship between prolactin (PRL) and testosterone with BMD. We also studied the controversial effect of steroid therapy on BMD in these patients. We measured BMD in the lumbar spine and at the hip in 20 SLE men (mean age 37 y) and in the controls ( n = 40). We measured PRL and testosterone in serum and saliva. The mean dose of prednisone at the time of study was 11.6 mg; and cumulative dose was 17.6 g. No significative decrease in BMD was detected in SLE males vs controls; either in the lumbar spine (1.00 ± 0.1 vs 1.05 ± 0.1 g/cm2) or in the femoral neck (0.84 ± 0.1 vs 0.87 ± 0.1 g/cm2). No patient or control had osteoporosis or fractures. We did not find any relationship between BMD and cumulative dose and baseline dose of corticosteroids. The mean values of PRL and testosterone (serum and salivary) were in the normal range. We did not find any correlation between BMD, PRL and androgens. This study did not show a loss in bone mass in SLE men on corticosteroid therapy.
Epidemiology and socioeconomic impact of skin disease in lupus erythematosus
Authors: Tebbe B. , Orfanos CE
Published: November 2007

The prevalence rates of systemic lupus erythematosus (SLE) may vary within 17-48/100 000 population worldwide. Although population-based epidemiological studies are still missing, the cutaneous variants of lupus erythematosus (LE) are 2-3 times more frequent than SLE itself. The most common age of onset is 20-40 y. Overall, cutaneous LE is regarded as a variant with less severe course and better prognosis. However, CDLE and SCLE last for many years and may lead, like SLE, to severe disability for work and limited life quality; also, a small proportion of patients with cutaneous LE develops SLE during the course of their disease. This implies considerable amount of medical management and costs for the community. Early recognition of cutaneous LE patients at risk to develop SLE and preventive measures against disease triggering factors are important tasks for physicians attending with cutaneous LE patients. It seems that signs of nephropathy, elevated ANA-titers and arthralgias may serve as prognostic predictors for transition into SLE.

Characteristic features of cutaneous LE are photosensitivity and female predominance. UV light is a major environmental triggering factor in cutaneous LE. Skin lesions may be induced or preexistent lesions may exacerbate due to UV light in up to 80-90% of all patients. Therefore, socioeconomic counseling of the young patients, for example choice of occupation and sun protection, are essentials in compliant patients. Also, since females are 3—6 times more frequently affected than males, the possibility of hormonal influences including pregnancy and estrogen- containing drugs should be discussed. Risk considerations for females wishing to become pregnant are required, and avoidance of estrogen-containing contraceptives should be recommended.
Effect of cyclophosphamide on leukocytic infiltration in the brain of MRL/lpr mice
Authors: Farrell M. , Šakić B. , Szechtman H. , Denburg J.A.
Published: November 2007

Neuropsychiatric manifestations are a poorly understood and potentially life-threatening complication of systemic lupus erythematosus (SLE). MRL/1pr mice spontaneously develop a lupus-like syndrome which is similar to the human disease in many respects, including behavioural abnormalities. Our previous findings indicated that the age at which infiltration of immune cells into the choroid plexus is first observed coincides with the appearance of behavioural dysfunction in MRL/1pr mice. This present study quantified leukocyte infiltration in relation to prolonged administration of cyclophosphamide (CY), a treatment effective in preventing some behavioural deficits. Compared to MRL + / + controls, saline-treated MRL/1pr mice had significantly more CD45-positive cells (leukocytes) and CD45R-positive (B) cells in the choroid plexus and in the brain parenchyma. A six week course of CY (100 mg/kg i.p.) significantly reduced the infiltration of CD45, but not of CD45R-positive cells into the choroid plexus of the MRL/1pr substrain. In addition, the presence of leukocytes correlated positively with measures on one behavioural test (floating in the forced swim test) but not on another test (novel object test). These findings suggest that CY treatment has a differential effect on the infiltration of leukocyte subtypes and strengthen the hypothesis that some abnormal behaviour in MRL/1pr mice may be related to the presence of immunocompetent cells in the brain.
Systemic lupus erythematosus with acanthosis nigricans, hyperpigmentation, and insulin receptor antibody
Authors: Baird J.S. , Johnson J.L. , Elliott-Mills D. , Opas L.M.
Published: November 2007

Acanthosis nigricans, insulin receptor antibody, and systemic lupus erythematosus are associated in the potentially lethal syndrome of type B insulin resistance. Hyperpigmentation has been reported rarely, while glucose intolerance is common in these patients. We report an adolescent girl with acanthosis nigricans, hyperpigmentation, insulin receptor antibody, and systemic lupus erythematosus without glucose intolerance. Insulin resistance may be mild or transient in some patients with type B insulin resistance. Resolution of skin lesions was noted during therapy of SLE, and was associated with disappearance of insulin receptor antibody.
The Prevalence of Systemic Lupus Erythematosus in Northern Ireland
Authors: Gourley IS , Patterson CC , Bell AL
Published: November 2007

Using six sources of patient ascertainment, 467 patients were initially identified as having a diagnosis of systemic lupus erythematosus (SLE) in Northern Ireland. The diagnosis was subsequently altered in 45 of these, either by the patient, their family, or their physician. The corrected source data were then reanalysed by the 'capture-recapture' technique, which suggested a further 71 patients missed during the initial identification process. Eighty-eight patients underwent physical examination, and 14 were found to have a diagnosis other than SLE. A final estimated figure of 415 patients was obtained, giving a point prevalence on August 1, 1993 of 25.4 per 100000 for the Province (95% confidence interval 22.1-28.7 per 100000).
Mycotic aneurysm of a coronary artery in SLE—a rare complication of salmonella infection
Authors: Howe HS , Wong Jsl , Ding ZP , Sivathasan C. , Ang B. , Koh WH , Feng PH
Published: November 2007

We describe a 27 y old female systemic lupus erythematosus (SLE) patient with salmonella bacteraemia who presented with fever, back pain and an enlarging heart size. A two dimensional echocardiogram (2D Echo) showed a mass in the right atrium. Subsequent computer tomographic (CT) and magnetic resonance imaging (MRI) studies showed that this had become a ring shaped lesion at the posterior end of the interventricular septum with an area communicating with the right atrial cavity. At operation a ruptured mycotic aneurysm of the right coronary artery was found. This is the first report of an SLE patient with a coronary artery mycotic aneurysm due to salmonella and the first reported case of survival following rupture of such an aneurysm.
Primary antiphospholipid syndrome emerging following thymectomy for myasthenia gravis: Additional evidence for the kaleidoscope of autoimmunity
Authors: Shoenfeld Y. , Lorber M. , Yucel T. , Yazici H.
Published: November 2007

The etiology of autoimmune diseases is multifactorial. In many of them the stimulation by a specific autoantigen is claimed to be responsible for the initiation of the disease. Alternatively, an autoimmune state may be induced by a pure dysregulation of the immune system. Such is the case in which severe systemic lupus erythematosus (SLE) is induced in young patients with myasthenia gravis following thymectomy. We have referred to this set of events as the 'kaleidoscope of autoimmunity'. Herewith, we would like to present another example of the kaleidoscope phenomenon, namely: the emergence of a full blown clinical presentation of the primary antiphospholipid syndrome (APS-recurrent thromboembolic phenomena, repeated fetal loss with high titers of anti-cardiolipid antibodies) in a 32 y old female with myasthenia gravis, two years following thymectomy.

Thymectomy in myasthenic patients may be associated with the emergence of new autoimmune conditions such as SLE and APS, pointing to the importance of immune dysregulation in the induction of these autoimmune diseases.