bluuebunny/crossref_metadata_2025 huggingface dataset:
Major Histocompatibility Complex Genes and Susceptibility to Systemic Lupus Erythematosus in Northern India
Authors: Mehra N.K. , Pande Ira , Taneja Veena , Uppal S.S. , Saxena S.P. , Kumar A. , Malaviya A.N.
Published: November 2007

Fifty-eight patients with systemic lupus erythematosus (SLE) from Northern India were tissue typed for HLA class I and II antigens. The results revealed an appreciable increase of HLA-DR4 (37.5%) among patients compared with controls (17.9%), P < 0.03. Additionally, haplotype B8-DR3 was encountered frequently in the patient group. The findings suggest an important role of MHC genes in influencing susceptibility to SLE.
Psychiatric Disorder in Malaysians with Systemic Lupus Erythematosus
Authors: Cheuk Ngen Chin  , Cheong Izham , Kong Norella
Published: November 2007

All 79 patients who attended a University Systemic Lupus Erythematosus (SLE) Clinic over a 6 month period were assessed using the Clinical Interview Schedule for psychiatric disorder. Using the ICD-9 Classification, 40 were found to have psychiatric disorder, 26 having depressive neurosis, six anxiety neurosis, five endogenous depression and three dementia. The group with psychiatric disorder had significantly poor family support as well as lack of a confidant compared to the group without psychiatric disorder (P < 0.01). There was no difference between the group with psychiatric disorder and those without psychiatric disorder in terms of age, duration of illness, ethnicity and severity of SLE. Psychiatric disorder is common affecting more than half the subjects and depression was the most frequent diagnosis.
Profiles of Cytokines (TNFα and IL-6) and Acute Phase Proteins (CRP and α1AG) related to the Disease Course in Patients with Systemic Lupus Erythematosus
Authors: Meijer C. , Huysen V. , Smeenk R.T.J. , Swaak A.J.G.
Published: November 2007

Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNFα and IL-6 in relation to serum levels of C-reactive protein (CRP) and α1-acid glycoprotein (α1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukine profiles. Significantly elevated TNFα levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNFα were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNFα and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised α1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNFα and IL-6 and also between the different cytokine (TNFα and IL-6) levels and acute phase protein (CRP and α1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNFα and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE. These data are also highly suggestive of an imbalance between TNF, IL-6 and the acute phase reaction.
Pulmonary Arterial Hypertension Responsive to Immunosuppressive Therapy in Systemic Lupus Erythematosus
Authors: Morelli Sergio , Giordano Marcello , De Marzio Paolo , Priori Roberta , Sgreccia Alessandro , Valesini Guido
Published: November 2007

Two female patients with recent diagnosis of systemic lupus erythematosus (SLE) are reported. Pulmonary arterial hypertension was diagnosed by Doppler echocardiography. Immunosuppressive therapy was started at the time of diagnosis of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the estimated pulmonary artery systolic pressure was substantially decreased from 78 to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant improvement of the clinical conditions.
Renal Biopsy in Systemic Lupus Erythematosus: Significance of Glomerular Thrombosis. Analysis of 108 Cases
Authors: Miranda Juan M. , Garcia-Torres Romeo , Jara Luis J. , Medina Francisco , Cervera Hernando , Fraga Antonio
Published: November 2007

We investigated the frequency and distribution of glomerular thrombosis (GT) in 108 renal biopsies of lupus patients and correlated this finding with the presence of anticardiolipin antibodies (ACLA). GT was present mainly in the diffuse proliferative form. The activity index was higher in those patients with GT (12.9 ± 4.7 vs 5.4 ± 4.1, P < 0.01). The more severe histologic features, necrosis and extracapillary proliferation were also related with GT. In 18 cases with repeated biopsy the best predictors for the subsequent development of glomerular sclerosis were fibrinoid necrosis (P < 0.01), glomerular infiltration (P < 0.01) and an activity index of 10 or more (P < 0.05). GT also showed to be an important prognostic factor for sclerosis, although no statistically significant. ACLA were investigated in 36 patients at the time of renal biopsy. There were nine positive cases and in three of them this finding was related to GT. We can conclude that GT is a relevant feature showing active lupus nephritis and that it is not related to the presence of ACLA.
Suicide in Patients with Systemic Lupus Erythematosus: A Clinical Analysis of Seven Suicidal Patients
Authors: Matsukawa Yoshihiro , Sawada Shigemasa , Hayama Takashi , Usui Hiroshi , Horie Takashi
Published: November 2007

Despite many suicidal cases in patients with systemic lupus erythematosus (SLE), literature on this subject is lacking. To elucidate and prevent this phenomenon, we re-evaluated the clinical records of seven suicidal patients with SLE. Six patients had photosensitivity and insomnia. At the time of the suicide attempt, hypocomplementemia was observed in five of six patients. Diffuse slowing on electroencephalograms were observed in four of five patients. One patient successfully committed suicide while on no therapy while five patients made their attempts under the tapering courses of steroids. Five patients manifested psychoses whereas two patients displayed no psychotic findings. All patients attempted suicide shortly after admission (mean time 20 days). The subsequent courses of the survivors who received more medication were favorable. Therefore, it appears that disease activity was not fully controlled in these patients. Furthermore, signs of an imminent suicide attempt were missed in some cases. Psychosis, insomnia, history of photosensitivity, an incompletely controlled disease state, receiving tapering steroid dose, diffuse slowings on electroencephalograms and the presence of hypocomplementemia appeared to be risks for attempting suicide in SLE. We would recommend that such patients be under psychiatric care for at least 2 months to prevent suicide. When the patient is still psychotic or unstable, further medical care will be required.
A vascular Osteonecrosis in Patients with SLE: Relation to Corticosteroid Therapy and Anticardiolipin Antibodies
Authors: Migliaresi Sergio , Picillo Ugo , Ambrosone Lucia , Di Palma Gaetano , Mallozzi Matteo , Tesone Elena R. , Tirri Giuseppe
Published: November 2007

Sixty-nine unselected SLE patients were studied to evaluate the prevalence of avascular osteonecrosis (AVN) and its relationship with steroid therapy and with anticardiolipin antibodies (aCL). All the patients were under treatment with corticosteroids. AVN occurred in seven of the 69 patients (10. 14%) and was not related to corticosteroid intake. Seventeen of the 69 patients were also treated with methylprednisolone pulse therapy (MPPT) and cumulated the highest corticosteroid doses but none of them suffered from AVN. Excluding the 17 MPPT-treated SLE patients, corticosteroid intake was significantly higher in the AVN-SLE patients.

Abnormal IgG and/or IgM aCL serum levels were found in two of the seven AVN-SLE patients and in 24 of the 62 non-AVN SLE, without a statistically significant difference. None of the seven AVN-SLE patients showed features of antiphospholipid syndrome.

We conclude that in SLE patients a continuous high-dose steroid treatment may be considered a risk factor for AVN. On the contrary, MPPT regimen may reduce this risk. Anticardiolipin antibodies might represent an added factor which could play a role in some patients but not in all.
Injections of Complexes made of dsDNA and Specific Polyclonal Antibodies Extend MRL LPR Mouse Survival: a Pilot Study
Authors: Lebrun Philippe , Burny Wivine , Cosyns Jean-Pierre , Saint-Remy Jean-Marie R.
Published: November 2007

Antibodies towards double-strain (ds) DNA are responsible for the development of lupus nephritis both in human and animal models. A method by which one would suppress the production of pathogenic idiotypes could therefore prevent the development of nephritis. To this end, we prepared polyclonal anti-dsDNA antibodies by immunoaffinity from a serum pool of MRL/MpJ- lpr mice, a strain that develops an early form of nephritis identical to its human counterpart. Antigen-antibody complexes were prepared by addition of dsDNA. Such complexes have the potential of altering the anti-DNA antibody response and boosting the production of specific anti-idiotypic antibodies. Two groups of 14 MRL lpr mice were treated by regular intraperitoneal injections of 10μg dsDNA-anti-dsDNA complexes or carrier buffer, starting at the age of 4 weeks, namely, prior to the appearance of nephritogenic anti-dsDNA IgG antibodies. We show here that such a treatment significantly extended the survival of treated mice compared with the control group. Five treated mice were still alive at month 11 compared with two in the control group. In addition, microscopic kidney examination at the time of death showed less lesions in the treated group compared with controls. This study indicates that complexes made of dsDNA and anti-dsDNA can delay the development of nephritis in the MRL lpr mouse strain.
Antibodies Against Platelet-Activating Factor in Patients with Antiphospholipid Antibodies
Authors: Barquinero Jordi , Ordi-Ros Josep , Selva Albert , Perez-Peman Pilar , Vilardell Miquel , Khamashta Munther
Published: November 2007

We have studied the specificity of antiphospholipid antibodies in 148 patients with autoimmune diseases, 120 patients with systemic lupus erythematosus and 28 with the primary antiphospholipid syndrome. In addition, 20 patients suffering from syphilis were studied. As a control group, 64 healthy volunteers were investigated. Patient and control serum samples were tested for binding to seven different phospholipid antigens by ELISA. Interestingly, 90% of the sera from syphilis patients and 6% of the autoimmune patients exhibited a significant binding to platelet-activating factor (PAF), a molecule similar to the structure of phosphatidylcholine. In addition, the IgG fraction from one of the lupus patients, which showed a high binding activity to PAF, was further affinity-purified using both liposomes and an affinity chromatography column. Preincubation of these antibodies with PAF inhibited subsequent binding to immobilized PAF. These observations might suggest a putative interaction of antiphospholipid autoantibodies with PAF 'in vivo', which may have, in some patients, important pathophysiological consequences.
Systemic Lupus Erythematosus: Predisposition for Uterine Cervical Dysplasia
Authors: Blumenfeld Z. , Lorber M. , Yoffe N. , Scharf Y.
Published: November 2007

A previous retrospective study has found an increased risk of uterine cervical atypia in women with systemic lupus erythematosus (SLE) who have been treated with cytotoxic drugs. Our objective was to prospectively reveal any increased incidence of cervical atypia in SLE patients and to evaluate the relationship to previous chemotherapy. A total of 39 SLE women were prospectively referred for cytologic PAP smears of the uterine cervix. A significantly higher incidence of cervical atypia was found in SLE women (35.9%) compared with non-SLE control groups (≤5%; P < 0.01). No significant difference was found between the incidence of atypia in patients previously treated by cytotoxic medications such as cyclophosphamide pulses or methotrexate (4 of 9) compared with SLE women not receiving cytotoxic drugs (10 of 30). Colposcopically directed biopsies revealed three cases of cervical intraepithelial neoplasia (CIN) I-III (23%) among the cases with atypia. We conclude that women with SLE should have regular cytologic cervical smears because of a significantly increased incidence of atypia, regardless of previous cytotoxic therapy.
Antiphospholipid Syndrome: Clinical and Therapeutic Aspects
Authors: Vlachoyiannopoulos Panayiotis G. , Tsiakou Eleni , Chalevelakis George , Raptis Sotiris A. , Moutsopoulos Haralampos M.
Published: November 2007

The purpose of the present study was to evaluate patients with the antiphospholipid syndrome with particular attention to their initial clinical features, final diagnoses and the course of thrombotic events in association with therapy. The methodology applied was the following: retrospective analysis of 30 patient files (20 female, 10 male) with antiphospholipid syndrome (APS). Four types of therapy were evaluated for their efficacy to prevent thrombotic recurrences, aspirin 100 mg daily plus low-dose prednisone 10-15 mg daily, warfarin (with international normalized ratio 2 to 2.6), immunotherapy alone and no therapy. None of the patients was followed-up during pregnancy. The probability of thrombosis-free survival was estimated according to Kaplan-Meier method, while the statistical significance was tested by the log rank test. There were 21 patients with primary APS and 9 with secondary, 8 of whom had SLE and one patient who had primary Sjögren's syndrome. The age at onset and the disease duration did not differ between men and women, while patients with secondary APS had a longer disease duration than patients with primary APS, a finding indicating that SLE patients develop, for unknown reasons, APS a long time after the initiation of their disease. Twenty patients experienced recurrent thrombotic events (a total of 46 recurrences) of which 43 (93%) were identical to the first event. Thus, in the majority of the cases arterial were followed by arterial and venous by venous thrombotic events: a finding suggesting a tissue-related factor for initiation of thromboses. Total follow-up of the patients was 154 patient years, of which 98 patient years were after the first thrombotic episode. More specifically: aspirin plus low-dose prednisone, 38 patient years; warfarin therapy, 15; immunotherapy alone, 10; no therapy, 35. The recurrence rates of thrombotic events were 0.13, 0.20, 0.70 and 0.88, respectively. The thrombosis-free survival after the first thrombotic event was significantly longer with aspirin plus low-dose of prednisone and warfarin therapy than with no therapy (P < 0.005 and P < 0.05, respectively). Immunotherapy alone did not prolong significantly the thrombosis-free survival compared with no therapy. Prospective studies are necessary to identify the optimum type and duration of therapy. Although immunotherapy and warfarin therapy cannot be definitely tested due to the small number of patients, the short follow-up and in the case of warfarin the low intensity of therapy, our data suggests that aspirin with low doses of prednisone and warfarin seem to be the most effective anti-thrombotic therapies in APS.
Solar Ultraviolet Radiation Induces Enhanced Accumulation of Oxygen Radicals in Murine SLE-Derived Splenocytes in vitro
Authors: Dov Golan Theo , Dan Sigal , Haim Hacham , Varda Gottfried , Sol Kimel
Published: November 2007

Although sunlight is known to induce generalized manifestation in systemic lupus erythematosus (SLE) patients, its underlying mechanism remains obscure. In the present study we have investigated whether UVA (320-400 nm), the most predominant UV component in solar radiation, induces enhanced accumulation of reactive oxygen species in murine SLE-derived cells (MRL/1) in comparison to normal cells (Balb/c), as measured by oxygen (O2) consumption, by means of a Clark-type electrode. Our data show enhanced O2 consumption by MRL/1 cells (which correlates with the formation of reactive oxygen species), accompanied by decreased viability, in comparison to irradiated normal cells. This finding suggests that increased accumulation of reactive oxygen species contributes to the enhanced photosensitivity observed in SLE patients.
Multiple Subungual Splinter Hemorrhages in the Antiphospholipid Syndrome: A Report of Five Cases and Review of the Literature
Authors: Francès Camille , Piette Jean-Charles , Saada Véronique , Papo Thomas , Wechsler Bertrand , Chosidow Olivier , Godeau Pierre
Published: November 2007

Multiple subungual splinter hemorrhages have been initially described as an important sign of subacute endocarditis. Secondly, they were reported in various other conditions, especially in isolated cases of primary antiphospholipid syndrome. We report five patients with multiple fingernail subungual splinter hemorrhages occurring in the course of antiphospholipid syndrome. Antiphospholipid syndrome was secondary to systemic lupus erythematosus in two, to Fasciola hepatica infection in one and was considered as primary in two. In all patients multiple subungual splinter hemorrhages occurred concomitantly with thrombotic events of diverse arterial sites. The mechanism of subungual splinter hemorrhages is most probably thrombotic.
Complete Heart Block in an Adult with Systemic Lupus Erythematosus
Authors: Fonseca Eduardo , Crespo Mariano , Sobrino Jose-Antonio
Published: November 2007

Report of a case of complete heart block in a patient with systemic lupus erythematosus (SLE). The cardiac disturbance presented as repeated syncopal episodes and normal cardiac clinical and electrocardiographic examination between these episodes. Circulating anti-UIRNP antibodies were detected and tests for anti-SSA/Ro, anti-SSB/La and antiphospholipid antibodies were negative. Evidence of myocarditis was not found. The diagnosis was just established when the patient developed a syncopal episode during hospitalization. Only one SLE case with a similar clinical course has been reported previously.
Conjugates or dsDNA Linked to Human Gammaglobulin Inhibit Anti-dsDNA Antibodies In Vitro
Authors: Mikael Nagy , Boguniewicz Mark , Manakata Yasuhiko , Sasaki Takashi , Borel Halina , Borel Yves
Published: November 2007

Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus eruthematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE.
SLE in Indian Men: Analysis of the Clinical and Laboratory Features with a Review of the Literature
Authors: Pande Ira , Malaviya A.N. , Sekharan N.G. , Kailash S.S. , Uppal S.S. , Kumar A.
Published: November 2007

Data on the clinical and laboratory profile of 39 male lupus patients has been analysed. An attempt has been made to (1) delineate the pattern of SLE in Indian males, (2) compare it with that reported in the world literature, (3) find out differences, if any, between male children and adults with the disease, and (4) compare it with our previously published data on Indian females with SLE. Several important points were brought out in this study. First, SLE in Indian males has an earlier age of disease onset, a higher incidence of mucocutaneous and renal involvement and a lower incidence of neuropsychiatric, gastrointestinal and hematological disease in comparison to those published from the developed countries. Second, leucopenia and lymphopenia, a reflection of disease severity, occur significantly more in male children compared with adults. Thrombocytopenia is exclusively noted in adult males and virtually non-existent in children. Third, male patients overall have a less severe form of the disease in comparison with their female counterpart, as was evident by significantly less patients with hypocomplementemia, diffuse proliferative lupus nephritis and psychosis. Finally, a higher frequency of infection, particularly tuberculosis, was seen in male patients, which was the cause of death in some.
Brain Reactive Autoantibodies and Cognitive Impairment in Systemic Lupus Erythematosus
Authors: Hanly John G. , Fisk John D. , Eastwood Brian
Published: November 2007

Nervous system involvement in SLE encompasses a wide array of clinical manifestations which may reflect multiple etiologic factors including autoantibodies to nervous tissue antigens. The aim of the present study was to examine the association between autoantibodies to a wide range of brain antigens and cognitive abnormalities in an unselected population of 70 SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared with 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Integral membrane proteins were isolated from dissociated brain cells by temperature-induced phase separation with Triton X-114. Synaptosomes were isolated by differential centrifugation and membrane enriched fractions were prepared by lectin affinity chromatography. Western blotting identified IgG reactivity to a wide range of proteins (MW 22-52K) in SLE patients. The proteins identified were distinct from well-characterized intracellular antigens including ribosomal P proteins. There was no significant difference in the prevalence of anti-brain antibodies between SLE patients who were cognitively impaired and those who were not impaired. Furthermore, there was no association between the presence of autoantibodies and subsets of cognitive dysfunction. These results suggest that circulating autoantibodies to brain antigens are not responsible for the abnormalities in cognitive function in SLE patients.
Anticardiolipm Antibodies: Specificity and Function
Authors: Harris E.N. , Pierangeli Silvia
Published: November 2007

Antibodies detected by solid phase anticardiolipin immunoassays are heterogeneous but understanding the nature of this heterogeneity has proven difficult. Differences in any of the following features may account for differences in anticardiolipin antibodies: avidity for cardiolipin, phospholipid cross-reactivity, specificity for β2 glycoprotein I (β2GPI)-cardiolipin complexes, functional activity (as defined by the ability to inhibit phospholipid dependent coagulation reactions) and specificities for different conformations of phospholipids. Understanding these differences may be important in explaining the variations in clinical presentation of patients with these antibodies. This review attempts to define and discuss anticardiolipin heterogeneity.
Models for Central Nervous System Complications of Antiphospholipid Syndrome
Authors: Hess David C.
Published: November 2007

One of the clinical hallmarks of antiphospholipid syndrome is the development of neurological complications, namely cerebral ischaemia, chorea, multi-infarct dementia, amaurosis fugax, migraine and transverse myelitis. An animal model should include the development of measurable neurological deficits and evidence of cerebral infarction. Although there are a number of mouse models for fetal loss, there has been no convincing model for the neurological complications of the antiphosphohpid syndrome. One explanation for the high frequency of neurological events in antiphospholipid syndrome is a vulnerability of the cerebral vasculature to the hypercoagulable state associated with the syndrome. A greater appreciation of the differences in the regulation of coagulation between the systemic and cerebral vasculatures may be key to understanding the apparent predilection for central nervous system involvement in the antiphospholipid syndrome.
'Primary', 'Secondary' and Other Variants of the Antiphospholipid Syndrome
Authors: Asherson Ronald A. , Cervera Ricard
Published: November 2007

Although the APS seen as a PAPS or accompanying SLE essentially manifests the same clinical features, there appears to be distinct differences in the two groups of patients which have been summarized in this article. Additionally, the fact that some patients with Sneddon's syndrome, Trousseau's syndrome, or even Addison's disease, may in reality be examples of aPL-related vascular occlusive events has opened new avenues, not only for identification of these patients, but also for more systematic therapeutic regimens.
Drugs Recently Associated With Lupus Syndromes
Authors: Fritzler Marvin J.
Published: November 2007

A number of drugs have recently been implicated in a syndrome that resembles systemic lupus erythematosus. One of the difficulties in many of these patients is that the signs, symptoms and serological abnormalities reported in these patients may be a natural consequence of the primary diseases rather than the incriminated drug. A second problem with the studies is a lack of unifom reporting of the techniques used to detect autoantibodies. For example, a patient that has a highly positive ANA with a homogeneous pattern of staining or a positive LE cell test usually has antibodies directed against chromatin components (DNA, histones, high mobility group (HMG) proteins). The discrepancies in clinical criteria and the serological techniques in many of these reports, emphasize the importance of using guidelines for the diagnosis of drug-induced or drug-related lupus. In the future, it appears that the increased use of biological response modifiers such as interferon-α and other cytokines may prompt more reports of lupus syndromes associated with their use.
Possible Role of Cytochromes P450 in Lupus Erythematosus and Related Disorders
Authors: McKinnon Ross A. , Nebert Daniel W.
Published: November 2007

Cytochromes P450 comprise a superfamily of enzymes pivotal in the metabolism of innumerable substrates of both endogenous and exogenous origin. The total number of distinct P450 genes, each encoding a different enzyme in humans, is estimated to be at least 60 and possibly several hundred. The cytochrome P450 (CYP) superfamily nomenclature system is based on divergent evolution of the genes. Most of the enzymes within gene families CYP1, CYP2, CYP3 and CYP4 appear to have evolved as the body's primary defense against the onslaught of chemicals confronted on a daily basis. Whereas P450 enzymes more than 3.5 billion years ago were undoubtedly designed as necessary components of signal transduction pathways, in the past billion years most P450 enzymes have become generally responsible for the detoxification of numerous foreign chemicals. During such oxidative metabolism, it has become increasingly apparent that these enzymes are also capable of functioning in an ambivalent manner, generating toxic intermediates. More than a dozen human P450 polymorphisms have been characterized. Genetic variability in P450 expression is therefore likely to have significant bearing on individual susceptibility to chemical toxicity. In this review, genetic differences in human P450 expression are outlined, and their possible relationship to autoimmune disease is examined. In addition, the speculative role of P450 polymorphisms in several 'lupus-like' disorders is discussed.
Role of T Cell DNA Methylation in Lupus Syndromes
Authors: Yung Raymond L. , Richardson Bruce C.
Published: November 2007

Current theories postulate that exposure to certain environmental agents will induce lupus in genetically predisposed individuals. However, the mechanisms by which environmental agents interact with the immune system to trigger lupus is unclear. Recent work has shown that some environmental agents associated with lupus, such as procainamide, hydralazine and ultraviolet light, will inhibit T cell DNA methylation, increase LFA-1 expression and induce autoreactivity. In addition, T cells isolated from patients with active lupus have hypomethylated DNA, diminished DNA methyltransferase activity and overexpress LFA-1 on an autoreactive subset of cells which spontaneously lyses autologous macrophages. More recent work has shown that the adoptive transfer of murine T cells made autoreactive with DNA methylation inhibitors is sufficient to cause a lupus-like disease in otherwise healthy syngeneic recipients. Together, these results support a new model of autoimmunity, in which certain environmental agents modify T cells by inhibiting DNA methylation and altering expression of certain genes, thereby inducing autoreactivity. The autoreactive cells then interact with the host to produce a lupus-like disease.
Impact of Ultraviolet Irradiation on Expression of SSA/Ro Autoantigenic Polypeptides in Transformed Human Epidermal Keratinocytes
Authors: Kawashima Toshimitsu , Zappi Eugene G. , Lieu Tsu-San , Sontheimer Richard D
Published: November 2007

SSA/Ro autoantibodies are frequently found in various autoimmune disorders including subacute cutaneous and neonatal lupus erythematosus. SSA/Ro patient sera precipitate a ribonucleoprotein complex consisting of multiple polypeptides and small RNA molecules (hY RNA). Such sera react in Western blot with at least four antigenically distinct proteins having molecular weights of 52-60 kD. Several laboratories have reported increased binding of anti-SSA/Ro patient serum to viable cultured human epidermal keratinocytes following UVB irradiation. However, it is currently unknown which SSA/Ro molecule(s) might be responsible for this increased antibody binding to UVB irradiated keratinocytes. To address this question, we studied the effect of UVB irradiation on the expression of three different polypeptide components of the SSA/Roautoantigen complex (60 kD SSA/Ro, 52 kD SSA/Ro, and 46 kD SSA/Ro (calreticulin) in A431 cells, a transformed human epidermal keratinocyte cell line. Total cellular and cell surface expression of each SSA/Ro antigenic polypeptide was examined by a whole cell ELISA and FACS using rabbit anti-synthetic peptide antisera as probes. Our results suggest that both total cellular and cell surface calreticulin, but not the 60 and 52 kD SSA/Ro polypeptides, is increased after 100J/M2 of UVB irradiation, indicating that perturbed calreticulin expression may be primarily responsible for the UVB-induced increased binding of anti-SSA/Ro to keratinocytes. These results suggest that calreticulin could be a critical component of the SSA/Ro ribonucleoprotein complex that is involved in the pathogenesis of anti-SSA/Ro-associated photosensitive LE skin lesions.
Anticardiolipin Antibodies and Polyarteritis Nodosa
Authors: De La Fuente Fernandez Raúl , Gil Jenaro Graña
Published: November 2007

A patient with biopsy-diagnosed polyarteritis nodosa showed central nervous system (CNS) involvement and evidence of intrathecal synthesis of immunoglobulins, coincident with very high serum levels of anticardiolipin antibodies (aCL). Cerebral angiography was normal. We suggest that aCL could be directly implicated in the CNS damage.
Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus
Authors: Choon Lee Wang  , Wang Florence , Bosco John Joseph
Published: November 2007

Ninety-two women with systemic lupus erythematosus treated with oral cyclophosphamide were studied to ascertain the prevalence and the factors associated with ovarian dysfunction. Menstrual disturbance during treatment occurred in 55% of patients: 36% had amenorrhoea and 19% had oligomenorrhoea. Sustained oligomenorrhoea occurred in 12% patients. Permanent amenorrhoea (> 12 months) after cessation of oral cyclophosphamide occurred in 27% of patients. Hormonal studies in these patients were consistent with ovarian failure. Older age at initiation of treatment and high cumulative dose of cyclophosphamide were found to be associated with this outcome. There was a trend towards linear relationship between the age of initiation of cyclophosphamide therapy and frequency of amenorrhoea. A statistically significant association between amenorrhoea and cumulative dose of cyclophosphamide after adjustment for age was found whereas no such association was linked to the duration of treatment. Fourteen of the 23 women who wished to become pregnant after cessation of treatment conceived resulting in 20 live births and two abortions.
A new endocrinological and immunological syndrome in SLE: elevation of human chorionic gonadotropin and of antibodies directed against ovary and endometrium antigens
Authors: Moncayo Roy , Moncayo Helga E
Published: November 2007

We have analysed the levels of gonadotropins in male and female patients with systemic lupus erythematosus (SLE). Human chorionic gonadotropin hCG was elevated in 23.8% of patients compared with 12.7% of controls. hCG isolated from the serum of SLE patients was bioactive in vitro. Levels of hCG were significantly correlated with those of its beta-subunit but not with the levels of follicle stimulating hormone, luteinizing hormone, prolactin alphafetoprotein or carcino embryonic antigen. A high percentage of patients presented an organ-specific humoral immune response against ovarian (26.7%) and endometrial (40%) antigens compared with controls (8% and 7.6%, respectively). Endometrial antibodies were significantly correlated to the levels of prolactin. The ovarian tumour marker CA-125 was elevated in 32.5% of patients, including two males. As a whole, these elements delineate a new endocrine and immunological syndrome in SLE in which the elevation of hCG could provide a central physiological explanation for a series of endocrine alterations that characterize this disease.
Lack of relationship between human immunodeficiency virus infection and systemic lupus erythematosus
Authors: Font Josep , Vidal Josep , Cervera Ricard , López-Soto Alfons , Miret Carles , Jiménez de Anta Maria Teresa , Ingelmo Miguel
Published: November 2007

The objective of this work was to determine whether HIV-1 and HIV-2 could be involved in the pathogenesis of systemic lupus erythematosus (SLE). Seventy-five consecutive Caucasian patients with SLE presenting at one institution over a 2-year period were studied. Serum samples were surveyed for anti-HIV-1 antibodies by a commercial ELISA coated with HIV-1-p24. For confirmation, conventional immunoblots were performed with the following antigens: HIV-1-gp41, p31, p24 and p17 (recombinant) and HIV-2-gp36 (synthetic peptide). Additionally, Western blots with HIV-1-gp160, gp120, gp41, p65, p51, p24 and p18 bands were applied.

Seventeen (23%) patients exhibited reactivity with HIV-1-p24 in the ELISA, but in the immunoblots and Western blots these sera samples were negative.

Patients with SLE may exhibit a reactivity with HIV-1-p24 in the ELISA for HIV infection screening but not in the confirmatory blots. This false-positive reactivity is probably due to molecular mimicry between autoantigens and retroviruses or a contaminant or artefacts in the antigen preparation procedure.
Association between HLA class II antigens and primary antiphospholipid syndrome from the South of Spain
Authors: Camps MT , Cuadrado MJ , Ocón P. , Alonso A. , Gutierrez A. , Guil M. , Grana MI , de Ramón E.
Published: November 2007

Recent studies have suggested an association between primary antiphospholipid syndrome (PAPS), antiphospholipid antibodies and some major histocompatibility complex (MHC) antigens. We have studied the relationship between MHC class II antigens and PAPS in 19 patients from the south of Spain. Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%1 P = 0.03), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04). However, multivariant analysis confirmed the association with DQ7 (RR = 2.5; CI 80%:1.3-4.7) and DR4 (RR = 2.2; CI 80%:1.1-4.4) but not with DQ3. When we introduced DRw53 into this analysis, we noticed a DR4 confounding effect, with DQ7 (RR = 3.1; CI 80%: 1.7-5.8) and Drw53 (RR = 2.3; CI 80%: 1.2-4.4) remaining as the most important HLA antigens related to PAPS. In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.
Hemiballismus in systemic lupus erythematosus: possible association with antiphospholipid antibodies
Authors: Tam Lai-Shan , Cohen Michael G , Li Edmund K
Published: November 2007

The neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are diverse but, among them, movement disorders are distinctly uncommon. We describe a 30-year-old female with SLE who developed sudden onset of right-sided hemiballismus. Previous cerebral venous thrombosis and a poor obstetric history suggested the antiphospholipid syndrome but only minimally elevated levels of anticardiolipin antibodies were detected. The underlying pathology could not be established but was most likely to have been a microinfarct of the contralateral subthalamic nucleus. Our patient responded rapidly to haloperidol alone without the requirement for corticosteroids.
Hepatic amyloidosis associated with systemic lupus erythematosus
Authors: García-Tobaruela Almudena , Gil Antonio , Lavilla Paz , Larrauri Javier , Pizarro Angel , Moreno de la Santa Carmen , López-Dupla Miguel , Martínez Pedro
Published: November 2007

The association between amyloidosis and systemic lupus erythematosus has rarely been described. We report a case of a 37-year-old man with a long-standing SLE who developed clinical and laboratory signs of hepatic dysfunction. A liver biopsy revealed secondary amyloidosis.
Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?
Authors: Balestrieri Genesio , Tincani Angela , Spatola Laura , Allegri Flavio , Prati Enrica , Cattaneo Roberto , Valesini Guido , Del Papa Nicoletta , Meroni Pierluigi
Published: November 2007

Anticardiolipin (aCL) and anti-beta2-glycoprotein I(antiβ2GPI) antibodies have been shown in animal models as not cross-reacting antibody populations. This observation prompted us to prove if anti-β2GPI exist in human sera by using a reliable method and then to investigate if these are independent from aCl antibodies. We have developed a new ELISA for the detection of anti-β2GPI antibodies employing the coating of the protein in carbonate buffer to irradiated microtitre plates and the filtration of serum samples, that makes irrelevant the binding to the uncoated wells. IgG F(ab)2 fragments from IgG positive sera were shown bind β2GPI, providing that the binding was a specific antibody binding, mediated by the antigen binding site of the antibody molecule; moreover the antibodies were not able to differentiate native and delipidated β2GPI coated plates, making a possible role of a phospholipid contaminant unlikely. On the other hand, the phosphorus content of native as well as delipitated β2GPI was undetectable. IgG, but not IgM, anti-β2GPI antibodies were classically inhibited by the addition of soluble β2GPI, while cardiolipin liposomes appear to modify the reaction in a completely different way, possibly by the described interaction between cardiolipin and β2GPI. The application of the new ELISA to the study of patients has shown that: (1) the presence of anti-β2GPI is statistically associated with the presence of aCL antibodies (P < 0.0001), (2) anti-β2GPI antibodies are related to the classical features of antiphospholipid syndrome (thrombosis: P < 0.001; fetal loss: P < 0.001) while, in this series of patients, aCl antibodies are not (thrombosis: P < 0.126; fetal loss: P < 0.061).
False positive seroreactivity to Borrelia burgdorferi in systemic lupus erythematosus: the value of immunoblot analysis
Authors: Weiss Nancy L , Sadock Victoria A , Sigal Leonard H , Phillips Mark , Merryman Parvin F , Abramson Steven B
Published: November 2007

The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot analysis as a tool to differentiate true from false positive ELISA. Sera were obtained from patients with SLE ( n = 35), rheumatoid arthritis ( n = 26), seronegative arthritis (n = 28) and Lyme disease ( n = 18). Reactivity to B. burgdorferi antigens was analysed by two available diagnostic techniques: ELISA and immunoblot. Correlations were made between seroreactivity to B. burgdorferi and standard serological tests of autoimmunity: antibodies to nuclear antigens, dsDNA, cardiolipin, SSA and SSB. Seroreactivity to B. burgdorferi antigens by the ELISA system was detected in 40% of patients with SLE, 8% of patients with rheumatoid arthritis and 4% with seronegative arthritis. Among patients seropositive by ELISA, immunoblots were negative in all cases. However, eight of 14 patients with rheumatoid arthritis (57%) showed cross-reactivity to multiple borrelial antigens. No significant correlations were found between Lyme seropositivity by ELISA and other autoantibodies except IgM rheumatoid factor (r = 0.61, P < 0.01 ) in patients with rheumatoid arthritis.

In conclusion: a positive ELISA for Lyme disease was found in up to 40% of patients with established SLE and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique. We conclude that immunoblot analysis can help differentiate a false from true positive ELISA for Lyme disease. These findings should caution the clinician with regard to the limitations of current diagnostic testing for Lyme disease, particularly in patients with connective tissue disease.
IgA antiphospholipid antibodies in HTLV-1-associated tropical spastic paraparesis
Authors: Wilson Wendell A , Morgan Owen St. C , Barton EN , Smikle M. , Hanchard B. , Blattner WA , Doggett Sarah , Gharavi Azzudin E
Published: November 2007

A retrovirus, human T cell lymphotropic virus type 1 (HTLV-1), is an essential but not a sufficient aetiologic factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for treponemal infections (BFP-STS), we used ELISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies occur in about 26% of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-1 or other non- treponemal infections.
Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion
Authors: Abu El-Asrar Ahmed M , Naddaf Hasan O , Al-Momen Abdul-Kareem , Al-Balla Suliman R
Published: November 2007

In this report we describe a patient with systemic lupus erythematosus who was clinically stable after treatment with the antimalarial drug chloroquine and pulse cyclophosphamide therapy. Three months after the discontinuation of chloroquine, the patient developed cilioretinal artery occlusion that was the only the manifestation of a clinical flare-up without evidence of clinical disease activity elsewhere. This case report confirms the clinical belief that the antimalarial agents can maintain the clinical quiescence of systemic lupus erythematosus and its discontinuation is associated with an increase in the risk of clinical flare-up.
Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus
Authors: Yood RA , Steigman DM , Gill LR
Published: November 2007

A 34-year-old woman with stable systemic lupus erythematosus (SLE) treated with low-dose prednisone and hydroxychloroquine developed multiple bilateral pulmonary nodules. Open lung biopsy documented lymphocytic interstitial pneumonitis (LIP). LIP should be considered in the differential diagnosis of nodular pulmonary lesions in patients with SLE.
Occasional Review: Use of hyperbaric oxygen in rheumatic diseases: case report and critical analysis
Authors: Wallace D.J. , Silverman S. , Goldstein J. , Hughes D.
Published: November 2007

Hyperbaric oxygen has been used in patients with rheumatic disease for many years without reports of untoward or unusual complications for a variety of non-rheumatic indications. Recent evidence that hyperbaric oxygen inhibits the actions of certain cytokines, acts as an immune modulator and may help cognitive dysfunction has resulted in a re-examination of its potential role in rheumatic diseases. A case report of a lupus/scleroderma crossover patient is presented whose cognitive dysfunction improved after hyperbaric oxygen therapy. The history of hyperbaric oxygen and its physiology are related, along with a focused review of its effects on the immune and central nervous systems. Areas which might warrant further consideration by rheumatologists are outlined, as well as areas of concern.
Severe hepatic involvement without inflammatory changes in systemic lupus erythematosus: report of two cases and review of the literature
Authors: Atsumi T. , Sagawa A. , Jodo S. , Amasaki Y. , Nakabayashi T. , Ohnishi K. , Fujisaku A. , Koike T.
Published: November 2007

Hepatic diseases in systemic lupus erythematosus (SLE) are not rare, but liver biopsies of those cases are usually reported as chronic hepatitis or steroid-induced steatosis. We describe two unusual patients with active SLE who displayed liver dysfunction without inflammatory changes or associated with drug administration. A liver biopsy in case 1 showed massive hepatic cell damage resulting in acute hepatic failure. In case 2, the liver specimen revealed diffuse fatty degeneration without symptoms specific to liver dysfunction. No inflammatory cell infiltrate was observed in the liver tissue of either patient. After steroid pulse therapy (case 1) and the administration of 60 mg/day of prednisolone (case 2), liver function improved in parallel with the stabilization of the other manifestations of SLE. No other causes for liver damage except for SLE were observed in either case. Therefore it is supposed that the liver impairments in these cases were one manifestation of SLE.
Penicillium marneffei infection in a patient with SLE
Authors: Lo C.-Y. , Chan D.T.M. , Yuen K.-Y. , Li F.-K. , Cheng K.P.
Published: November 2007

We describe a patient with SLE who was infected by the fungus Penicillium marneffei. She was initially misdiagnosed as having disseminated tuberculosis. The correct diagnosis was finally made by bone marrow culture and she responded to a prolonged course of amphotericin B, flucytosine and itraconazole. The clinical presentation and histology of penicilliosis are very similar to those of Mycobacterium tuberculosis. In Southeast Asia, penicilliosis should be considered as a differential diagnosis in patients with SLE who present with fever and lymphadenopathy.
Systemic lupus erythematosus and anticardiolipin antibodies in Klinefelter's syndrome
Authors: Miyagawa S. , Matsuura E. , Kitamura W. , Ohno H. , Kichikawa K. , Uchida H. , Shirai T. , Okamoto S.
Published: November 2007

A case report of Klinefelter's syndrome is presented that shows features of systemic lupus erythematosus, arteriographically-proven peripheral artery occlusion with leg ulcers, multiple cerebral infarcts and persistent elevations of anticardiolipin antibodies.