bluuebunny/crossref_metadata_2025 huggingface dataset:
Transverse myelitis as a first manifestation of systemic lupus erythematosus: a case report
Authors: Lopez Dupla M. , Khamashta M.A. , Sanchez A.D. , Ingles F.P. , Uriol P.L. , Aguado A.G.
Published: November 2007

Transverse myelitis as a first manifestation of systemic lupus erythematosus (SLE) is very uncommon. No pathognomonic clinical or biochemical characteristics exist, and therefore an early diagnosis is often difficult. Therapy with intravenous pulses of methylprednisolone and cyclophosphamide has been shown to improve the prognosis. However, morbidity and mortality rates in transverse myelitis are still high due to the fact that complications such as opportunistic infections and pulmonary embolism are still frequent causes of death. We report a woman with relapsing transverse myelitis which was the first manifestation of SLE. A good response to pulse methylprednisolone and cyclophosphamide therapy was obtained but she died later as a result of a pulmonary embolism. We conclude that intravenous pulse methylprednisolone and cyclophosphamide therapy improve the prognosis of transverse myelitis associated with SLE but that a careful follow-up is needed to avoid complications due to the illness itself or secondary to the therapy.
Factors associated with mood and mood disorders in SLE
Authors: Shortall E. , Isenberg D. , Newman S.P.
Published: November 2007

This study examines the relative contribution of factors associated with anxious and depressed mood, and clinical anxiety and depression in SLE. Eighty sequentially consenting patients attending a rheumatology outpatient clinic were assessed on measures of anxiety and depression; disease activity; presence of autoantibodies; neuropsychological performance; and psychological and social factors. Mood and mood disorders were found to be unrelated to measures of disease activity but were found to be associated with psychological and social factors. These findings emphasise the importance of psychosocial factors in attempts to understand mood and psychological distress in SLE.
Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery
Authors: Raz E. , Dudler J. , Lotz M. , Baird S.M. , Berry C.C. , Eisenberg R.A. , Carson D.A.
Published: November 2007

Somatic gene therapy is a novel approach with the potential to achieve prolonged increases in circulating levels of peptide hormones and cytokines. The present study evaluates the effects of monthly, intramuscular injections of cDNA expression vectors encoding for transforming growth factor β (TGFβ) or interleukin 2 (IL-2) on disease activity in the MRL/lpr/lpr murine model of systemic lupus erythematosus (SLE). Monthly injections of plasmids cDNA between 6 and 26 weeks significantly elevated the serum levels of TGFβ (P < 0.005) and IL-2 (P < 0.05) compared with a control plasmid without insert. TGFβ encoding plasmid had beneficial effects in murine SLE with a prolonged survival of 70% at 26 weeks compared with 40% in the control group, decreased anti-chromatin and rheumatoid factor antibodies and a 50% decrease in total IgG production. Renal function was improved with reduced BUN levels and kidney inflammation as estimated by an histologic score. Those beneficial effects occurred in the apparent absence of local or systemic side-effects. In contrast, IL-2 cDNA injections appeared harmful with a decreased survival to 20% at 26 weeks, enhanced total IgG synthesis and autoantibodies production with a 4.5-fold increase in anti-chromatin antibodies. These results indicate that somatic gene therapy may provide a simple, inexpensive and effective mechanism for the long-term control of autoimmune diseases.
Dual inhibitory and stimulatory activities in serum from SLE patients and lupus mice that regulate the proliferation of an IL-2-dependent T cell line
Authors: Huang F.-P. , Stott D.I.
Published: November 2007

In serum and plasma from SLE patients, we have detected elevated levels of factors which regulate proliferative responses of CTLL cells to IL-2. Serum samples containing these factors have dose-dependent dual inhibitory and stimulatory activities on the proliferation of this IL-2-dependent T lymphocyte cell line. At high concentrations, the serum factors inhibit the proliferative responses of CTLL cells to IL-2. At low concentrations, they synergise with IL-2 stimulating the growth of cells. Similar inhibitory activity, but with lower titre, was also found to be elevated in sera of some MRL/ lpr mice, an animal model of SLE. Functional characterisation of the serum factors shows that: (1) the inhibitory activity cannot be neutralised by exogenous IL-2; (2) the stimulatory activity is not due to the presence of serum IL-2 but synergy of the factor with IL-2; (3) the factors bind directly to CTLL cells but they do not bind to protein A; and (4) the serum factors are not dialysable but heat labile. The possible pathological implications of the serum factors, particularly for the defective T cell functions in lupus disease, are discussed.
Specific antiphospholipid antibodies (aPL) eluted from placentae of pregnant women with aPL-positive sera
Authors: Katano K. , Aoki K. , Ogasawara M. , Sasa H. , Hayashi Y. , Kawamura M. , Yagami Y.
Published: November 2007

The mechanism by which antiphospholipid antibodies (aPL) cause recurrent pregnancy loss remains unclear. It has however been reported that aPL may affect cytotrophoblasts in vitro and thus direct placental damage might occur. Therefore, we investigated whether aPL are bound directly to placental tissues in patients with immunoglobulin G (IgG) -aPL positive sera.

The material investigated comprised the placentae of six patients with a history of recurrent pregnancy loss and subclinical autoimmune disorder and one with systemic lupus erythematosus, who were treated with a combination of prednisolone and aspirin. Normal controls consisted of placentae derived from six women, negative for serum aPL, with no medical or obstetrical complication during their pregnancy.

Five kinds of IgG- and IgM-antiphospholipid (anti-PS, PI, PA, PG and CL) antibodies were eluted from the placentae of both patients and controls, which were measured by enzyme-linked immunosorbent assay.

IgG-aPL were detected in the placental eluates of four of seven (57%) patients, whereas IgM-aPL were not found in any. With respect to the pregnancy outcome of the four patients with IgG-aPL-positive placental eluates, one experienced intrauterine fetal death (IUFD) at 23 weeks of gestation and three demonstrated intrauterine growth retardation (IUGR). In contrast, the remaining three patients, evaluated negative for IgG-aPL in placental eluates, gave birth to one baby with IUGR and two appropriate-for-date babies. The placentae of the four mothers with IgG-aPL-positive placental eluates pathologically showed severe thrombotic findings.

These results suggest that IgG-aPL can directly bind to placental tissue and might cause pathologic damage resulting in IUFD or IUGR.
The presence of antiphospholipid antibodies in acute myocardial infarction
Authors: Adler Y. , Finkelstein Y. , Zandeman-Goddard G. , Blank M. , Lorber M. , Lorber A. , Faden D. , Shoenfeld Y.
Published: November 2007

This study was undertaken to determine if there is an association between increased titers of five different antiphospholipid antibodies (aPLA) in young patients' sera and the occurrence of acute myocardial infarction (AMI). Antibodies to anticardiolipin (aCL), anti-phosphatidylserine (aPS), antiphosphatidylinositol (aPI), anti-phosphatidylcholine (aPC), and anti-phosphatidylethanol amine (aPEA) were measured in 214 patients (102 patients, 102 healthy controls and 10 patients with antiphospholipid syndrome). These antibodies were measured twice (within 4 h of onset of acute myocardial ischemic chest pain and 3 months after the myocardial infarction) by enzyme linked immunosorbent assay (ELISA).

Elevated titers of four different aPLA were detected in 6.9% of all patients with AMI on hospitalization. Titers of aPLA in AMI were elevated in the younger age group <50 years old (P < 0.001) and in men only (not statistically significant). No correlation was found between the presence of aPLA and cardiovascular risk factors (smoking, hypertension, diabetes mellitus and hypercholesterolemia). Three of the seven patients with increased titers of aPLA did not have any other cardiovascular risk factors. The titers of aPLA were within normal range 3 months after AMI.

Evidence of significantly elevated titers of different aPLA at the early stage of AMI suggests that these autoantibodies are present before the AMI and are not secondary to them. The disappearance of the elevated aPLA 3 months after AMI may be due to an absorption effect or possibly a cyclic phenomenon similarly found in other autoimmune diseases. aPLA may be an additional risk factor for AMI, and should especially be considered in a patient of the younger age group without apparent cardiovascular risk factors.
Tricuspid Valve Steno-Insufficiency in Systemic Lupus Erythematosus
Authors: Morelli S. , Perrone C. , Valesini G.
Published: November 2007

We describe a case of isolated tricuspid steno-insufficiency, diagnosed by transthoracic echocardiography, in a 43-year-old woman affected by systemic lupus erythematosus. Other similar cases were never previously reported.
Hemichorea in systemic lupus erythematosus: significance of MRI findings
Authors: Al Jishi F. , Al Kawi M.Z. , El Ramahi K. , Omer S.
Published: November 2007

A young man with systemic lupus (SLE) developed hemichorea 13 years after the onset of his illness. For the first time in the course of his illness he had a positive test for anticardiolipin antibodies (aCL). Magnetic resonance imaging (MRI) of his brain showed lesions of presumed vascular cause in the ipsilateral hasal ganglia. The findings support the contention that an immune phenomenon, invisible on proton imaging by MRI, is responsible for the striatal neuronal activation. Chorea, the clinical expression of this activation, was probably blocked on the side previously affected by vascular pathology.
Prolactin and systemic lupus erythematosus: prolactin secretion by SLE lymphocytes and proliferative (autocrine) activity
Authors: Gutiérrez MA , Molina JF , Jara LJ , Cuéllar ML , García C. , Gutiérrez-Ureña S. , Gharavi A. , Espinoza LR
Published: November 2007

Accumulated evidence suggests that prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). Moreover, a PRL-like molecule is secreted by normal human lymphocytes and acts as an autocrine growth factor for lymphoproliferation. The objective of this study was to explore the PRL-like peptide production by peripheral blood mononuclear cells (PBMC) from patients with SLE.

We investigated the PRL secretion by PBMC from six female SLE patients and nine normal subjects (5 women and 4 men). Ficoll-Hypaque isolated PBMC (1 X 106 cells/ml) were cultured with and without maximal stimulatory doses of PHA (1 mg/ml) or PWM (1/200). At 72 h of culture supernatants were harvested and used to determine PRL immunoreactivity by a radioimmunoassay (NIDDK-reagents). Cell extracts and concentrated supernatants were prepared to determine PRL by Western blot analysis (NIDDK-reagents).

SLE non-stimulated PBMC secreted significantly higher levels of PRL than normal non- stimulated PBMC (8.09 ± 4.15 ng/ml vs. 3.48 ± 2.36 ng/ml, P = 0.02 by Mann-Whitney test). High levels of PRL were secreted by SLE-PHA stimulated PBMC (6.88 ± 4.53 ng/ml) and SLE-PWM stimulated PBMC (16.57 ± 16.39 ng/ml) compared with normal-PHA stimulated PBMC (5.83 ± 5.27ng/ml) and normal-PWM stimulated PBMC (8.54 ± 5.49ng/ml), respectively, but the differences were not significant. The maximal production of PRL was found in PWM-stimulated lymphocytes in both groups. Cells extracts prepared from SLE non-stimulated and stimulated PBMC contained a 11 KDa PRL immunoreactive material. Concentrated supernatants from SLE non-stimulated and stimulated PBMC contained both a 11 KDa and a 24-27 KDa PRL immunoreactive material.

Our data indicate that PBMC from patients with SLE have an increased production of PRL-like immunoreactive material. This PRL is released in vitro as two different molecular weight forms, and appears to be derived from B rather than T lymphocytes.
Longitudinal measurement of anticardiolipin antibodies during normal pregnancy: a prospective study
Authors: Lynch AM , Rutledge JH , Stephens JK , Murphy JR , Marlar RA , Davila GH , Santos ME , Emlen W.
Published: November 2007

We have previously shown that elevation of anticardiolipin antibodies (aCL) at the first prenatal visit is associated with increased fetal loss in normal pregnancy. The variation in aCL levels during normal pregnancy has not been established. To examine this question we measured IgG, IgM and IgA aCL levels five times during pregnancy at weeks 5-15, 16-25, 26-35, 36-37 and at delivery. Data were analyzed to determine: (a) the within and between subject variability of aCL during pregnancy; (2) the temporal trend of aCL; and (3) the relation of serial measures of aCL with maternal complications of pregnancy.

We divided our cohort of 354 subjects into two groups. Group A included those subjects with consistently normal levels of aCL and group B those subjects with at least one elevated level of aCL. In group A the within subject variability was relatively low (28-34%). In group B we found wide fluctuations in aCL levels and a within subject variability of 88-91 %. Subjects in group B had no increase in maternal complications of pregnancy.

The present data suggest that aCL may fluctuate significantly during normal pregnancy and there is little clinical value in measuring aCL on a serial basis during pregnancy.
Analysis of three new idiotypes on human monoclonal autoantibodies
Authors: Kalsi JK , Ravirajan CT , Wiloch-Winska H. , Blanco F. , Longhurst CM , Williams W. , Chapman C. , Hillson J. , Youniou P. , Latchman D. , Isenberg DA
Published: November 2007

We have identified and characterised three new idiotypes on human IgM McAbs generated from the splenocytes of a SLE patient with active disease. RT-6, which binds H1 and Sm/RNP, expresses essentially a private Id. Its expression is limited to a small number of human McAbs and the sera from patients with infectious diseases. In contrast RT-72Id and RT-84Id, expressed on McAbs which are polyreactive for two or more antigens, have a public distribution. RT-72Id and RT-84Id are found on McAbs from murine and human adult, and foetal tissues. In sera, significant numbers of SLE, RA and patients with other autoimmune diseases are positive for both Ids. RT-84Id is also elevated in SLE relatives and spouses, and in patients with Klebsiella infection. No correlation with disease activity, IgM or IgG levels was observed with either Id. However, RT-72Id was significantly associated with anti-ssDNA antibodies and RhF. RT-6Id and RT-72Id are located on the framework regions of the μ heavy chain, whereas RT-84Id is present on the kappa light chain, within the binding site. The McAbs are encoded by mainly germline genes: heavy chains of RT-6, RT-72 and RT-84 are encoded by the genes VH26, VH4.22 and VH4.21, respectively, and the light chain sequences of RT- 6 and RT-72 are derived from DPL11 and HK102. Immunofluorescent staining revealed the presence of RT-72Id and RT-84Id positive immunoglobulin deposits in 18% and 45%, respectively, of the lupus renal sections compared with none in the disease control group, suggesting that these Ids may contribute to the pathology of the disease.
Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity
Authors: Houssiau FA , Lefebvre C. , Vanden Berghe M. , Lambert M. , Devogelaer J-P. , Renauld J-C.
Published: November 2007

We investigated whether serum titers of interleukin 10 (IL-10), a cytokine known to shift lymphocyte responses towards humoral immunity, reflect disease activity in systemic lupus erythematosus (SLE). Sera from 72 SLE patients, 25 RA patients and 30 healthy controls were tested for IL-10 by ELISA. Low titers of IL-10 were detected in the serum of 37.5% of SLE patients and in 24% of RA patients but in only 3% of healthy controls. Interestingly, serum IL-10 titers in SLE patients were positively correlated with the SLE Disease Activity Index (SLEDAI) and with anti-DNA antibody titers, but negatively with complement fraction C3 levels. These results indicate that serum IL-10 values reflect SLE disease activity and suggest that overexpression of IL-10 might play a pathogenic role in severe lupus disease.
Cytomegalovirus infection induces expression of 60 KD/Ro antigen on human keratinocytes
Authors: Zhu J.
Published: November 2007

To investigate the effect of human cytomegalovirus (CMV) infection on the expression of Ro autoantigen in human keratinocytes, the binding of anti-Ro peptide antibodies (anti-60 KD/Ro, anti- 52 KD/Ro and anti-calreticulin) to cultured human keratinocytes was detected by fixed cell enzyme- linked immunoassay (ELISA), immunofluorescence, flow cytometry (FACS) analysis and immunoblotting. There was a significant increase in the binding of anti-60 KD/Ro antibody but not anti-52 KD/Ro or anti-calreticulin antibody to the surface of cultured keratinocytes at 24 h after CMV infection compared with uninfected cells, by ELISA and immunofluoresence. Surface binding of anti-60 KD/Ro was found in 71.2% (±5.5%) of CMV-infected cells compared with 26.2% (±4.1%) of untreated cells (P < 0.05) by FACS analysis. Similar observations were made with a human serum which contained anti-60 KD/Ro antibodies. Immunoblotting was used to analyse total cellular 60 KD/Ro antigen expression in keratinocytes infected with CMV or without infection. No increase in the intensity of the 60 KD band was found in extracts of the CMV-infected cells, suggesting that the 60 KD/Ro antigen is redistributed from the cytoplasm to the cell surface after viral infection. The effects of CMV infection on cell cultures were compared with those of ultraviolet B (UVB) irradiation. The 60 KD/Ro, 52 KD/Ro and calreticulin were all induced on the UVB-irradiated cell surface but no significant synergistic effect of UVB and CMV was found. This study provides evidence that CMV infection induced 60 KD/Ro antigen expression on the surface of human keratinocytes, suggesting that CMV may play a role in development of skin lesions in systemic lupus erythematosus (SLE).
Special report: adjusted lupus prevalence Results of a marketing study by the Lupus Foundation of America
Authors: Lahita R.G.
Published: November 2007

There are many estimates of the prevalence of systemic lupus erythematosus. These range from a high of 1:245 to 1:1000 from numerous worldwide epidemiologic studies. In a departure from scientific procedure the Lupus Foundation of America recently completed an inexpensive marketing study which produced three findings. Firstly, that lupus awareness in the USA was about 86%, much higher than many other immunologic illnesses. Secondly, that many people have been told by their physicians that they have the disease lupus, and considering that data, that over 1.4 million people in the USA have the disease. Lastly, that the prevalence of the disease, by unsubstantiated claim, would be a very high 1 in 177 patients. The overall conclusion is that more people are being told that they have the disease lupus than previously expected. Self-reporting studies are notoriously inaccurate as the criteria for the disease are not verified, indicating that the numbers derived from this study may not be true.
Immunomodulating effects of synchronised plasmapheresis and intravenous bolus cyclophosphamide in systemic lupus erythematosus
Authors: Hanly J.G. , Hong C. , Zayed E. , Jones J.V. , Jones E.
Published: November 2007

Recent studies have suggested that synchronised plasmapheresis and intravenous pulse cyclophosphamide therapy reduce disease activity in SLE patients. The aim of the present study was to examine the immunomodulating effects of this therapy and compare it with changes seen with cyclophosphamide alone. Four patients with active SLE were studied. Two were treated with synchronised therapy and two received cyclophosphamide only for up to 26 weeks. Disease activity was measured by the SLE disease activity index (SLEDAI). Immunological studies were performed immediately prior to each treatment. Patients in both treatment groups improved as reflected by a fall in mean SLEDAI scores: synchronised therapy 33.5 to 11; cyclophosphamide only 13.5 to 4.5. Following synchronised therapy only there was a prompt and sustained increase in the mean percentage of CD8 + cells (20.8 to 54.8) which resulted in a fall in the CD4:CD8 ratio (1.95 to 0.62). With both treatment modalities there was a fall in the proportion of CD20+ cells (B lymphocytes) (synchronised therapy 10.5 to 3.2; cyclophosphamide only 5.6 to 2.2). However, only synchronised therapy resulted in a fall in the in vitro production of immunoglobulins which was unchanged or increased following cyclophosphamide alone. These results suggest that although both treatment modalities are efficacious in the treatment of active SLE they produce different immunomodulatory effects. Thus, both therapies reduce the number of circulating B lymphocytes whereas synchronised therapy also modifies cellular immunity by promoting the emergence of a phenotypic suppressor T lymphocyte population.
Human T cell responses to autoantibody variable region peptides
Authors: Williams W.M. , Staines N.A. , Muller S. , Isenberg D.A.
Published: November 2007

The origins and regulation of autoantibodies in SLE may involve idiotypic cell interactions. The purpose of this study was to determine if SLE patients have T cells reactive with the idiotopes of autoantibodies. Sequences of the variable regions of two DNA-binding autoantibodies (Vλ of antibody B3 and VH of 9G4) were selected according to the predicted location of their idiotypes defined previously by anti-idiotypic antibodies. The sequences were prepared as synthetic 16mer peptides (idiopeptides). Peripheral blood mononuclear cells were prepared from SLE patients (n = 28) and controls (n = 13) and put into multiple microcultures with idiopeptide for 6 days. The frequency of responding cultures was determined as those incorporating thymidine at levels above the mean plus three standard deviations of the control cultures lacking peptide. Of the 28 lupus patients, six responded to B3 idiopeptide and five to the 9G4 idiopeptide. Some patients responded to other idiopeptides, but only one normal individual responded to each reference peptide. The difference between the patient and control responses to all idiopeptides was significant by χ2 analysis (P = 0.025). We conclude that patients with SLE show evidence of sensitisation of T cells to idiotopes of autoantibodies. Such anti-idiotypic T cells could either provide idiotype-specific help or suppression for autoantibody responses in SLE.
Role of β2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease
Authors: Dueymes M. , Piette J.C. , Le Tonquèze M. , Bendaoud B. , Roué R. , Garré M. , Youinou P.
Published: November 2007

The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of β2-glycoprotein I (β2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that β2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when β 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.
Choroidopathy in a case of systemic lupus erythematosus
Authors: Abu El-Asrar A.M. , Naddaf H.O. , Mitwali A.
Published: November 2007

Choroidopathy in association with systemic lupus erythematosus (SLE) has rarely been reported. We report a patient with SLE and choroidopathy manifested by bilateral multifocal, serous elevations of the neurosensory retina. Control of the systemic disease resulted in resolution of the serous detachment.
Occasional Series: Lupus Around the World Systemic Lupus Erythematosus Research in the Asia-Pacific Region: A co-ordinated and co-operative approach
Authors: Fong K-Y. , Feng P-H.
Published: November 2007

Research on SLE in the Asia-Pacific region is presently conducted separately in various centres. A co-ordinated and co-operative approach is advocated for a long-term, prospective study on lupus patients in this region. A pilot study involving Beijing, Shanghai and Singa pore has been initiated with the intention of expanding it to a larger study, involving up to 1000 newly diagnosed lupus patients who will be followed up for 10 years. The study design and term definitions are patterned after that of the Euro-Lupus project so as to allow for meaningful comparisons. The protocol was discussed, pretested and revised before arriving at the final version to be used. The principal co-ordinators met and discussed with all pioneer participating rheumatologists to ensure common understanding of definitions and standardisation of laboratory procedures. Preliminary results are expected to be presented in about six months' time together with an invitation for more rheumatologists to partici pate in the project.
Biochemical characterization of ADP-ribose polymer metabolism in SLE
Authors: Chen H-Y. , Pertusi RM , Kirkland JB , Rubin BR , Jacobson EL
Published: November 2007

The metabolism of poly(ADP-ribose) in peripheral blood mononuclear (PBM) cells was studied in 13 patients with systemic lupus erythematosus (SLE) and in 12 age and sex matched controls. Poly(ADP-ribose) polymerase activity was measured as the net accumulation of ADP-ribose polymers during the conversion of 32P-NAD to poly(ADP-ribose) in PBM cells in vitro. The control population showed a mean activity of 418 ± 91(s.d.) pmol ADP-ribose/10 min/106 cells. The SLE population was more heterogeneous and showed a lower mean of 225 ± 147(s.d.) pmol ADP-ribose/ 10 min/106 cells. The mechanism of decreased ADP-ribose polymer accumulation was investigated. Measurements of turnover of the ADP-ribose polymers and its substrate, NAD+, showed that diminished ADP-ribose polymer accumulation in SLE subjects resulted from decreased poly(ADP- ribose) synthesis and not from altered rates of polymer turnover or NAD utilization. Western blot analyses of enzyme protein levels, kinetic studies of poly(ADP-ribose) polymerase activity and analyses of polymer size distribution suggested that the mechanism of poly(ADP-ribose) synthesis in SLE cells is not altered but that the number of active poly(ADP-ribose) polymerase molecules is reduced.
Prolactin levels and antinuclear antibody profiles in women tested for connective tissue disease
Authors: Allen SH , Sharp GC , Wang G. , Conley C. , Takeda Y. , Conroy SE , Walker SE
Published: November 2007

Hyperprolactinemia has been reported in some patients with active systemic lupus erythe matosus (SLE). To determine if there was an association between selected autoantibodies and hyperprolactinemia, we assayed prolactin concentrations in sera from women sub mitted to a reference antinuclear antibody laboratory. Autoantibody-positive samples were separated into groups that contained antibodies to double-stranded DNA (anti-DNA), anti bodies to SSA/Ro (anti-SSA/Ro), or antibodies to both SSA/Ro and SSB/La (anti-SSA/Ro- SSB/La). Results were compared with autoantibody-negative sera from age-matched women, submitted to the same laboratory. We also compared the study groups with a separate cohort of 84 healthy women who were not referred for autoantibody testing. Elevated prolactin levels were clustered in 20% of sera from anti-DNA-positive women ≤50 years of age. Twenty-one percent of anti-SSA/Ro-SSB/La-positive women < 50 years of age were hyperprolactinemic. Four of the 15 hyperprolactinemic women identified in this survey had no known cause of elevated prolactin. In the other 11 individuals, secondary causes such as hypothyroidism, pregnancy, chronic renal failure, and medications may have accounted for high serum prolactin values. We also examined sera by Western blot, to determine if immunoblot patterns were associated with elevated serum prolactin concentra tions. The hyperprolactinemic sera yielded novel bands migrating at 70 kd, 32 kd, and 16.5 kd.

This study confirmed the reported associations of hyperprolactinemia with SLE and Sjögren's syndrome. Multiple factors appeared to contribute to elevated serum prolactin levels in women with connective tissue diseases, and the presence of hyperprolactinemia was related to unique findings on immunoblot analysis.
Respiratory function in systemic lupus erythematosus: relation with activity and severity
Authors: Rolla G. , Brussino L. , Bertero MT , Bucca C. , Converso M. , Caligaris-Cappio F.
Published: November 2007

The objective of this study was to examine the relation between respiratory function tests, disease activity and disease severity in ambulatory patients with systemic lupus erythematosus (SLE) who did not present with overt respiratory problems. Lung volumes, maximal expiratory flows at 50% and 25% of vital capacity (MEF50 and MEF25), bronchial threshold to methacholine (PD15FEV 1), transfer factor CO (KCO) were measured in 24 consecutive SLE outpatients (22 women, age 41 ± 14.8 years) and in 24 healthy controls matched for age and sex. In SLE patients alveolar-arterial oxygen gradient (AaO2) was also measured. Disease activity was assessed by European Consensus Lupus Activity Measurement (ECLAM) scoring system and disease severity by Lupus Severity of Disease Index. In comparison to controls SLE patients showed a significant decrease of total lung capacity (TLC) (91.7 ± 16.5 vs 102.7 ± 12.9% predicted, P < 0.01), MEF25 (58.4 ± 25.2 vs 73.5 ± 19.5% predicted, P < 0.005), PD15FEV1 (2164 ± 1122 vs 4230 ± 1014 μg methacholine, P < 0.0001) and KCO (77.1 ± 20.5 vs 96.3 ± 12.4% predicted, P < 0.001). AaO2 (mean value 13.2 ± 8.4) was abnormally high (>20 mm Hg) in 12 patients. The ECLAM score of activity was inversely related with KCO (r = 0.48, P < 0.02). The severity index was significantly related with FEV1/VC ratio (r = 0.43, P < 0.05), MEF50 (r = 0.51, P < 0.01), MEF25 (r = 0.40, P < 0.05) and PD15FEV1 (r = 0.51, P < 0.01). In eight patients, evaluated also after treatment intensification, there was a significant increase in KCO (from 71.8 ± 24.7 to 84.9 ± 22.3% predicted, P < 0.01) along with a decrease in ECLAM score (from 3.0 ± 1.34 to 0.69 ± 0.75, P < 0.01).

The relation between disease activity and KCO suggests a relation between systemic and alveolar inflammation whereas the relation between severity index, airway patency and reactivity indices suggests a cumulative damage to the airways in SLE patients, even in the absence of overt respiratory manifestations.
Systemic lupus erythematosus after heavy exposure to quartz dust in uranium mines: clinical and serological characteristics
Authors: Conrad K. , Mehlhorn J. , Lüthke K. , Dörner T. , Frank K-H.
Published: November 2007

Epidemiological, clinical and serological data of uranium miners with symptoms of connec tive tissue diseases (CTD) were collected during the control examinations for occupational lung diseases since 1975. Twenty eight definite (four or more ARA criteria) and 15 probable (2-3 ARA criteria) SLE were diagnosed. The estimated prevalence among heavily silica exposed uranium miners was up to 93 in 100000. The only significant differences to non- exposed SLE patients were decreased frequency of arthritis and photosensitivity and the absence of anti-Sm and anti-U1-RNP antibodies. ANA were found in all definite SLE patients examined with the following specificies: anti-dsDNA (in 44.4%), & anti-Ro/SSA (in 55.6%, four cases together with anti-dsDNA) and anti-La/SSB (in 22.2%). The autoanti body profiles of patients with probable SLE were similar, but with a lower frequency of ANA, anti-dsDNA and anti-Ro/SSA. Middle to high-titred autoantibodies to dsDNA, Ro/SSA and La/SSB were detected in 3.2% uranium miners with no (N = 1229) and in 20.6% with some symptoms (one ARA criterion and/or two or more of other CTD typical symptoms, N = 68) of CTD development. We conclude, that the strong exposure to dust with a high content of silica may predispose to or initiate the development of SLE. The detection of SLE-typical antibodies in quartz dust-exposed miners may indicate a higher risk for the development of systemic autoimmune disease.
The significance of anticardiolipin antibodies in patients with lupus nephritis
Authors: Abu-Shakra M. , Urowitz MB , Gladman DD , Ritchie S.
Published: November 2007

The objective of this study was to determine whether anticardiolipin antibodies (ACL) in SLE patients are associated with a specific pattern of lupus nephritis and/or with renal microvascular changes. Patients with SLE, followed prospectively between June 1991-May 1994 at The Wellesley Hospital Lupus Clinic, who underwent a renal biopsy were included. The ACL was measured by the ELISA according to international standardized method. Renal biopsy morphology was assessed using the WHO criteria for the classification of lupus nephritis. Renal vascular changes included glomerular hyaline thrombi, intimal fibro sis and intraluminal thrombi of renal arterioles. There were 23 SLE patients. The mean age at diagnosis of SLE was 28.2 years and the mean disease duration was 6.3 years. Of these 10 (43%) had high levels of ACL. No difference in the frequency of severe nephritis (Class III and IV) was identified amongst patients with and without ACL. Mesangial nephritis was more common in patients with ACL 40% vs 0, p = 0.02). Glomerular hyaline thrombi occurred in 3 (13%) patients. None of them had positive ACL. Renal vascular lesions included intimal proliferation in 4 (ACL + , 1) occluded lumens by thrombi in 2 (ACL + 1). Our data indicate that the development of glomerular and/or microvascular changes is not related to the presence of ACL.
Primary antiphospholipid syndrome evolving into systemic lupus erythematosus
Authors: Derksen RHWM , Gmelig-Meijling FHJ , de Groot PhG
Published: November 2007

A young woman had a history of spontaneous venous thromboembolic disease which recurred on several occasions after cessation of treatment with oral anticoagulants. The presence of antiphospholipid antibodies (lupus anticoagulant and a high titre of IgG class anticardiolipin antibodies) in the absence of other clinical and serological features of sys temic lupus erythematosus (SLE) confirmed a diagnosis of primary antiphospholipid syn drome (PAPS). Antinuclear antibodies (ANA) were positive (1 :1280; speckled pattern). Twelve years after the first thrombotic episode she fulfilled criteria for the classification of SLE (antinuclear antibodies, platelet count < 100 x 109/l, anti-dsDNA antibodies, Coombs' positive haemolytic anaemia). She suffered a myocardial infarction while adequately anti coagulated and developed polyarthritis and immune complex-mediated nephritis over the next 3 years. This case history supports suggestions made by others that a strongly positive ANA test in a patient diagnosed with PAPS may be a harbinger for the development of SLE. Such evolution can take place over more than 10 years.
Correction of severe thrombocytopenia with chloroquine in the primary antiphospholipid syndrome
Authors: Suarez IM , Diaz RA , Canela D-Aguayo , Pujol de la Llave E.
Published: November 2007

We describe a patient with Primary Antiphospholipid Syndrome (PAPS) and severe throm bocytopenia with bleeding, in whom treatment with high dose steroids failed to maintain a sustained level of platelets following an initial short lived response. After several unsuc cessful attempts with Danazol and aspirin combined with low dose steroids, the platelets count rose following the administration of chloroquine and low dose steroids and remained in the normal range even when steroids were tapered.
Factors associated with fetal losses in severe systemic lupus erythematosus
Authors: Martinez-Rueda JO , Arce-Salinas CA , Kraus A. , Alcocer-Varela J. , Alarcón-Segovia D.
Published: November 2007

We evaluated factors associated with fetal losses in patients with severe lupus in a nested case-control study. We assessed separately 73 pregnancies that occurred in 46 women from a cohort of 633 Systemic Lupus Erythematosus (SLE) patients. They had at least one preg nancy after SLE diagnosis, one or more of our severity criteria and all had taken immuno suppressive drugs. Included data were related to disease severity, anti-phospholipid syndrome (APS), anticardiolipin antibodies (a-CL ab), and drugs received during preg nancy. Cases were pregnancies with fetal wastage; controls were pregnancies with live-born children.

The mean age at pregnancy was 26.6 ± 4.5 years. Cases had longer disease duration, 6.1 ± 3.5 years vs 4.5 ± 4.3 of controls (p = 0.02); higher prevalence of renal involvement, hemolysis and recurrent venous thrombosis (p < 0.05); they also tended to have a greater prevalence of a-CL ab, and previous fetal losses (p = 0.06). Cases used azathioprine more frequently than controls (p = 0.04). Univariate analysis showed an association of renal involvement, hemolytic anemia, azathioprine or cyclophosphamide prescription during pregnancy, previous fetal losses and APS with fetal wastage. Immunosuppressive drugs and the APS remained significant in the multivariate analysis (p = 0.05; F = 0.01). Factors related with fetal losses in women with severe SLE were: longer disease duration, ingestion of immunosuppressive drugs during pregnancy and any related manifestation of APS. We did not find macroscopic malformations in live-children of women that took azathioprine during pregnancy.
Antibodies reactive with HIV-1 antigens in systemic lupus erythematosus
Authors: Gül A. , Inanç M. , Yilmaz G. , Öcal L. , Koniçe M. , Aral O. , Badur S. , Dilşen N.
Published: November 2007

Antibodies reactive with retroviral gag proteins have been detected in patients with systemic lupus erythematosus (SLE). We investigated the immune responses against human immuno deficiency virus (HIV) 1 antigens in the sera of 44 Turkish patients with SLE. Serum samples were tested by using two different commercial enzyme immunoassay (EIA) kits and by Western blotting. EIA studies revealed positive results in 12 patients (27%) for HIV-1 antigens by one of the kits that coated with purified viral antigens. Immunoblot analysis showed antibodies mainly to retroviral gag proteins in 23 patients (52%). The most frequent reactivity was against the p18 gag protein (n = 9). Although antibodies reactive particularly with p24 antigen were described in the previous reports, antibodies to p24 were found in only two patients. These findings might reflect a serologic diversity in different ethnic groups and also suggest the involvement of different triggers in the etiopathogenesis of SLE.
Brain calcification in patients with cerebral lupus
Authors: Raymond AA , Zariah AA , Samad SA , Chin CN , Kong Nct
Published: November 2007

Cerebral lupus (CL) is a common cause of morbidity and mortality in patients with SLE. The brain CTs of 27 consecutive adult patients with SLE and various neurological presen tations were reviewed. The median age and duration of neurological symptoms at the time of the brain CT were 30 years (range = 14-51 years) and six days (range = 1 day-22 years), respectively. Eleven patients (41%) had normal CTs. The abnormalities in the remaining patients could be divided into six categories: (a) cerebral atrophy alone (two patients); (b) calcification alone (three patients); (c) infarct(s) alone (five patients); (d) cerebral atrophy and calcification (three patients); (e) cerebral atrophy and infarct(s) (one patient) and (f) cerebral atrophy, calcification and infarct(s) (two patients). Altogether eight patients (30%) (age range = 17-47 years) had intracerebral calcification : the globus pallidus was involved in all, putamen in two, head of the caudate nucleus in one, thalamus in one, centrum semiovale in two and cerebellum in three patients. Two patients had extensive calcifications of most of the basal ganglia, centrum semiovale and cerebellum. There was no relationship between the presence/degree of calcification and age of patients/duration or type of neurological presentation. The pathogenesis of cerebral calcification in CL is unknown. Cerebral lupus must now be included in the differential diagnosis of intracerebral calcification.
Abnormal prostanoid metabolism in lupus nephritis and the effects of a thromboxane A2 synthetase inhibitor, DP-1904
Authors: Yoshida T. , Ichikawa Y. , Tojo T. , Homma M.
Published: November 2007

Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB 2, 6-keto-PGF1α,2,3-dinor-6-keto-PGF1α and PGE2, and plasma level of 11-dehydro-TXB2 were determined. The effects of four days' dosing of a selective thromboxane A2 (TXA2 ) synthetase inhibitor, DP-1904 (DP), on pros tanoid metabolism, were also studied.

Urinary excretion of TXB 2, which reflects the renal production of TXA2, was signifi cantly increased in the patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1α ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbal ance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1α ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001).

DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2 and urinary TXB2/6-keto- PGF1α ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment.

The conclusions reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2 syn thetase inhibitor.
The role of β2-glycoprotein I in the antiphospholipid syndrome
Authors: Krilis SA , Sheng YH , Kandiah DA
Published: November 2007

Antiphospholipid antibodies were originally thought to bind negatively-charged (aniomic) phospholipids. Current evidence suggests that the target antigen is considerably more complex and includes β2-glycoprotein I, a phospholipid-binding plasma protein. Our under standing of the pathophysiology of the antiphospholipid syndrome has increased exponen tially with a number of studies into the interactions of antiphospholipid antibodies and β2-glycoprotein I.
Occasional Series: Lupus Around the World The Chilean experience of systemic lupus erythematosus
Authors: Massardo L. , Jacobelli S.
Published: November 2007

The Chilean experience with SLE began more than 40 years ago. The first series was published in 1958 with 108 patients. Lupus hair was described for the first time as a symptom that highly suggested SLE at that time. Subsequent studies have dealt with differ ent clinical aspects of the disease. The description of silent nephropathy in SLE and inspira tory muscle dysfunction as a cause of unexplained dyspnoea have been relevant contributions to the understanding of this condition. Patient survival has improved over the last decades from 13% at 5 years in 1959 up to 87% in 1994. Reasons for this improved survival are probably related to better diagnosis and management of the severely ill patients. However, in spite of this, the incidence of infections in our patients often contrib utes to fatal outcome. Recently, some studies have been published related to the basic pathogenic mechanisms of this disease.
A comparison of five health status instruments in patients with systemic lupus erythematosus (SLE)
Authors: Gladman DD , Urowitz MB , Ong A. , Gough J. , MacKinnon A.
Published: November 2007

The aim of the present investigation was to assess and compare health status instruments in SLE. One hundred and twenty-five patients completed five health status instruments: the Health Assessment Questionnaire (HAQ), Functional Ability Index, the Fatigue Severity Scale (FSS), the Disability Days Measure (DDM), the Centre for Epidemiological Studies- Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Short Form Health Survey during their Clinic visit. Disease activity was measured using the SLE Disease Activ ity Index (SLEDAI).

All instruments described a spectrum of quality of life outcomes in these patients. An inter-instrument correlation analysis revealed that components of the MOS correlated sig nificantly with each of the other instruments used. There was no correlation between any of the instruments used and the SLEDAI.

We conclude that health status assessment as measured by the MOS short form is a valid independent outcome measure in patients with SLE.
Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus
Authors: Martini F. , Farsi A. , Gori AM , Boddi M. , Fedi S. , Domeneghetti MP , Passaleva A. , Prisco D. , Abbate R.
Published: November 2007

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet.

Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasmin ogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL ( p < 0.01) and to controls ( p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.