bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma homovanillic acid and prolactin in systemic lupus erythematosus
Authors: Ferreira C , Paes M , Gouveia A , Ferreira E , Pádua F , Fiuáza T
Published: November 2003

Prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of pituitary prolactin secretion is complex and involves a negative feedback process in the hypothalamus, in which dopamine plays the principal role. However, the main source of serum prolactin in lupus patients is still not clearly established. Since homovanillic acid (HVA), the principal metabolite of dopamine (DA), is removed from the brain into the blood, it would indirectly reflect DA metabolism. It is assumed that the turnover of a neurotransmitter can be determined through an analysis of its metabolites. The objective of this study was to analyse plasma samples from SLE patients to see if there were any alterations in neurally functioning DA through its principal metabolite, HVA. We also measured the levels of PRL and compared HVA and PRL with the clinical activity of the disease. Twenty-four SLE patients and fifteen healthy controls were studied. The investigation was done over a period of 3 months.

The results of this study show significantly low levels of HVA in lupus patients compared to controls (P < 0.0001). This corresponds to a decrease in dopamine turnover. Hyperprolactinemia was observed in nine patients, and the average level of prolactin in lupus patients was higher than in healthy controls (P < 0.001). For the duration of the study, a significant percentage of variation was observed in the levels of HVA in the clinically active patients (P < 0.05) compared to inactive patients. When PRL was compared in these groups, throughout the study, no signifcant percentage of variation was observed. The relationship between HVA and PRL in healthy controls was r = 0.47, P=0.08, and in patients was r = 0.04, P = 0.84. It is suggested that there is a probable association between plasma levels of HVA and PRL in the healthy controls and not in the SLE patients.
Clinical significance of serum and urine prolactin levels in lupus glomerulonephritis
Authors: Miranda J M , Prieto R E , Paniagua R , Garcia G , Amato D , Barile L , Jara L J
Published: November 2003

Prolactin (PRL) has been involved in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia has been connected with systemic activity. However, the clinical significance of PRL has not been investigated in lupus glomerulonephritis (GN). Methods: We studied SLE patients (ACR criteria) with biopsy-proven renal disease. Renal histology was classified according to World Health Organization (WHO) criteria. Renal function tests, albuminuria, complement levels (nephelometry), anti-DNA antibodies (C. luciliae) and serum and urine PRL concentrations (RIA) were determined at baseline and at 4-month intervals for one year. Renal activity was defined as mild, moderate or severe according to serum creatinine, creatinine clearance, albuminuria, red blood cells (RBC), and casts. Results: There were 26 patients with mean age 28.5 y and mean disease duration 47.9 months. Twenty patients had diffuse proliferative glomerulonephritis (GN), four had focal GN and two had membranous GN with proliferative changes. Renal activity was mild in ten patients, moderate in ten and severe in six. Mean serum (24.7 5.3) and urine (0.90 0.36) PRL levels were higher in patients with severe renal activity (P < 0.05 compared with mild group). PRL levels decreased after treatment, but this trend was not uniform during the follow-up period. Conclusion: Hyperprolactinemia was prevalent in SLE patients and high levels of PRL in the serum and urine could be related to severe renal disease.
Bromocriptine in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled study
Authors: Alvarez-Nemegyei J , Cobarrubias-Cobos A , Escalante-Triay F , Sosa-Muüoz J , Miranda J M , Jara L J
Published: November 2003

The objective of this study was to investigate the efficacy and safety of bromocriptine (BRC) as an adjunct to conventional treatment in systemic lupus erythematosus (SLE). A prospective, doubleblind, randomized, placebo-controlled study compared BRC at a fixed daily dosage of 2.5 mg with placebo. Patients were followed for 2–17 months (mean 12.5 months). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), numbers of flares were recorded, and serum prolactin (PRL) levels were obtained at intervals during the study. Patients were allowed to take prednisone and immunosuppressive drugs.

Sixty-six patients with SLE entered the study. Thirty-six were treated with BRC, and 30 controls received placebo. Sixteen patients were removed from the study during the treatment period: five in each group left the study because of adverse effects, five became pregnant, and one patient who took placebo died with central nervous system lupus. Four patients in the BRC treatment group and three patients in the placebo group moved away or stopped coming for study visits for unknown reasons, and were lost to follow-up during the course.

At entry, serum PRL was (mean–s.d.) 24.8 ng/ml–18.4 in the BRC treatment group. This value fell to 5.8–9.0 after 12 months of treatment. Corresponding PRL values in controls were 23.7–22.1 pretreatment and 20.3–14 after 12 months. PRL levels in BRC-treated subjects were significantly lower than levels in control subjects after 3, 6, 9, and 12 months of treatment. The SLEDAI score on the fifth protocol visit was decreased significantly in the BRC group vs controls: 0.9–1.4 vs 2.6–4.5 (P < 0.05). Although the absolute number of flares in each group was similar, the mean number of flares/patient/month was decreased significantly in the BRC group compared to the control group (0.08–0.1 vs 0.18–0.2, P = 0.03).

Long term treatment with a low dose of BRC appears to be a safe and effective means of decreasing SLE flares in SLE patients.
Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus
Authors: Gutiérrez M A , Garcia M E , Rodriguez J A , Rivero S , Jacobelli S
Published: November 2003

The objective was to study the response of cortisol and of prolactin (PRL) to specific stimuli in systemic lupus erythematosus (SLE). We measured the response of cortisol to insulin-induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in seven patients with active untreated SLE and in ten paired control subjects. All were women with regular menstrual cycles. With the exception of two patients, they had never received corticosteroids before the study.

The basal serum levels of cortisol (12.5 2.4 μg/dl) and PRL (10.7 1.0 ng/ml) in the SLE group were not significantly different from those of the control group (12.3 1.1 mg/dl and 13.7 2.4 ng =ml, respectively). The cortisol response after hypoglycemia was significantly lower in SLE patients compared to the control group at 45 min (P = 0.01), at 60 min (P = 0.009), and at 90 min (P = 0.001). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1447 187 vs 1828 84, P = 0.06). Although the peak of PRL after TRH did not differ significantly in both groups (68.0 7.4 ng =ml in SLE vs 66.3 77 ng/ml in controls) and the AUC of PRL response after TRH was comparable in both groups (4672 537 vs 4128 541, P = 0.32), the interval-specific ‘delta’ response was significantly higher in SLE than the control group at 0–60 min (P = 0.02) and 0–90 min (P = 0.01) after TRH injection.

These findings suggest that active SLE is associated with some degree of dysfunction of the hypothalamic-pituitary-glucocorticoid axis and PRL secretion.
Differential effects of estrogen and prolactin on autoimmune disease in the NZB/NZW F1 mouse model of systemic lupus erythematosus
Authors: Elbourne K B , Keisler D , McMurray R W
Published: November 2003

Estrogen and prolactin have been shown to modulate autoimmunity in the NZB/NZW F1 (B/W) mouse model of systemic lupus erythematosus (SLE). However, estrogen stimulates prolactin secretion. The goal of this study was to examine differential effects of estrogen and prolactin in the female B/W mouse model of SLE. B/W females were manipulated to create combinations of low and high concentrations of serum estrogen and prolactin. Hyperprolactinemic mice with either low or high serum estrogen levels had accelerated development of albuminuria at 24 and 32 weeks of age compared to normal and hypoprolatinemic mice. High estrogen/high prolactin mice also had a higher percentage of anti-DNA antibodies compared to mice in the low estrogen/low prolactin and the high estrogen/low prolactin groups. IgG levels were not significantly different between groups. Mean survival was shortest in the high estrogen/high prolactin group (34 1.0 weeks) and longest in the high estrogen/low prolactin group (42 1.2 weeks; P < 0.05). High levels of serum estrogen were associated with depressed in vitro lymphoproliferation and IL-2 production. This study suggests that high prolactin levels in either high or low serum estrogen states are associated with accelerated autoimmunity in the B/W mouse. This study further demonstrates that high estrogen levels do not accelerate murine SLE when the prolactin-stimulating property of estrogen is suppressed by bromocriptine. Further investigation of hormonal interactions in autoimmunity will provide a better understanding of hormonal immunoregulation and, perhaps, lead to improved clinical application of hormonal immunomodulation.
Rheumatoid nodules in a patient with primary antiphospholipid (Hughes) syndrome
Authors: Elkayam O , Yaron M , Brazowski E , Caspi D
Published: November 2003

A 29-year-old woman presented with multiple rheumatoid nodules in both hands. Clinical features and supportive laboratory investigations revealed antiphospholipid syndrome. A review of rheumatoid nodules and cutaneous manifestations of antiphospholipid syndrome is presented.
Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans Syndrome
Authors: Musso M , Porretto F , Crescimanno A , Bondi F , Polizzi V , Scalone R , Mariani G
Published: November 2003

Immunoablation followed by allogeneic stem cell (SC) transplantation has been shown to be capable of curing a large spectrum of experimental autoimmune disorders, hereditary and/or induced. Superimposable results, albeit with some exceptions, have been obtained in human patients affected by coincidental autoimmune and blood diseases. However, both because of encouraging experimental results and of the procedure's greater safety, autologous SC are being increasingly utilized worldwide. Case reports are being collected in the registry of the European Group for Blood and Marrow Transplantation (EBMT)/European League against Rheumatism (EULAR) Autoimmune Disease Stem Cell Project.

Among the severe autoimmune diseases (SADs), which are the target of autologous transplantation, severe refractory systemic lupus erythematosus (SLE) is a condition which may benefit from this procedure. We report here the case of a 19 year old female patient with a six year history of SLE with secondary antiphospholipid syndrome (APS), who later developed refractory Evans syndrome. She was transplanted with autologous mobilized CD34+ SC and progenitor cells after conditioning with cyclosphosphamide, anti-T lymphocyte globulin and prednisone. Eight months after transplant, the patient is alive and well, with normal blood counts and persistent lowtitre direct antiglobulin (DAT, Coombs) and anti-nuclear antibody (ANA) tests. Anti-double stranded DNA antibody (Anti-dsDNA), lupus anticoagulant tests and anti-cardiolipin antibody (ACA) test are negative.
Successful treatment with immunosuppression, anticoagulation and vasodilator therapy of pulmonary hypertension in SLE associated with secondary antiphospholipid syndrome
Authors: Tam L-S , Li E K
Published: November 2003

Severe pulmonary hypertension (PHT) occurring in patients with systemic lupus erythematosus (SLE) is uncommon. Different modalities have been tried in the treatment for this condition but have not been effective because of progressive increase of pulmonary resistance over time. Our patient with SLE and PHT with antiphospholipid syndrome (APS), a condition which has previously never been described, responded rapidly to combination treatment with immuno-suppression, anticoagulation and vasodilator therapy.
Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome
Authors: Gordon C , Kilby M D
Published: November 2003

Systemic lupus erythematosus and antiphospholipid antibody syndrome are associated with an increased risk of intrauterine growth restriction, miscarriage, stillbirth and premature delivery. Recent advances in therapy during pregnancy have improved the outcome but there is still significant fetal and maternal morbidity and mortality. Treatment of patients failing conventional therapy during the second half of pregnancy is difficult and may be complicated by the development of preeclampsia. The addition of intravenous immunoglobulin therapy offers a low risk strategy for reducing autoantibody mediated disease and improving placental function in severely compromised, growth restricted pregnancies.
Vascular complications of diabetes mellitus: what role for phospholipid-binding antibodies?
Authors: Galtier-Dereure F , Biron C , Vies M , Bourgeois V , Schved J-F , Bringer J
Published: November 2003

Vascular complications are the main cause of morbidity in diabetes mellitus. However, the risk factors for vascular disease remain uncompletely elucidated. It has been previously suggested that factors other than glycemia may contribute to the development of vasculopathy. In this study we determined the prevalence of phospholipid-binding antibodies in uncomplicated and complicated diabetes.

We studied 53 uncomplicated diabetic patients, with type 1 (n=32) or type 2 (n=21) diabetes; 23 diabetic patients with proliferative retinopathy; 28 diabetic patients with an overt nephropathy; 37 diabetic patients with macroangiopathy and 22 non diabetic control patients. Both lupus anticoagulant and anticardiolipin antibodies were determined.Other risk factors for macroangiopathy were analysed.

The prevalence of phospholipid-binding antibodies was similar in uncomplicated diabetic patients and in controls (type 1 diabetes: 9.4%; type 2 diabetes: 9.5%; control group: 4.6%; P=0.76). In complicated diabetes, the frequency of these antibodies was increased only in patients with overt nephropathy (32.1%, P=0.01) or with macroangiopathy (32.4%, P=0.01) while patients with isolated retinopathy were comparable with uncomplicated diabetic patients (4.3%, P=0.66).Uncomplicated diabetes was not associated with phospholipid-binding antibodies. We found a higher prevalence of these antibodies in diabetic patients with macroangiopathy or nephropathy. These results suggest a potential role of phospholipid-binding antibodies in the progression of vascular complications in diabetes mellitus.
Fibromyalgia in Indian patients with SLE
Authors: Handa R , Aggarwal P , Wali J P , Wig N , Dwivedi S N
Published: November 2003

One hundred and fifty-eight patients with SLE were prospectively studied at a tertiary referral centre in India to ascertain the prevalence and clinical profile of fibromyalgia (FM) in Indian patients with lupus. An attempt was made to determine whether socio-demographic factors or disease characteristics differ in SLE patients with and without FM. Only 13 patients (8.2%) in our cohort were found to have fibromyalgia. Their clinical profiles were similar to that reported in other series. Corticosteroid withdrawal or dose reduction was the probable precipitating factor in nearly one-third of our patients. Age, sex, marital status, educational level, disease duration, disease activity and the organ involvement in patients with SLE and FM were comparable to those in patients not having FM. Fibromyalgia appears to be distinctly uncommon in Indian patients with lupus. A strong family support system, the virtual lack of disability benefits and/or racial variations in pain threshold could be the likely factors responsible for the low prevalence of the disease observed in Indian patients with SLE.
Visual disturbance by lymphocytic hypophysitis in a non-pregnant woman with systemic lupus erythematosus
Authors: Katano H , Umemura A , Kamiya K , Kanai H , Yamada K
Published: November 2003

The authors present the case of a patient with systemic lupus erythematosus who developed visual distubance and amenorrhea. Though the clinical and radiological findings resembled those of pituitary adenoma, the patient was finally diagnosed as having lymphocytic hypophysitis after the operation. We briefly describe this relatively rare entity in relation to its autoimmune pathogenesis.
Mucocutaneous disease in Arabs with systemic lupus erythematosus: Clinical expression and relevance to autoantibodies
Authors: Al-Attia H M , Al Ahmed Y H
Published: November 2003

Both criterial and non-criterial mucocutaneous manifestations of 42 Arabs with systemic lupus erythematosus are reviewed. Photosensitivity occurred in 40.5%, malar rash in 35.75% and oral ulcers in 26% of patients. Subcutaneous nodules and subcutaneous lupus erythematosus (SCLE) were not seen, and there were few cases of discoid rash (DLE), Raynaud's phenomenon, livedo reticularis and SLE-related sicca and anticardiolipin syndromes. In the clinical relevance of autoantibodies in these patients, there was a significant association between anti-Sm antibodies and oral ulcers (P = 0.033) and, interestingly, between anti-cardiolipin (aCL) antibodies and lack of photosensitivity (P = 0.014). The report also reviews previously presented data on mucocutaneous LE in Arab and non-Arab patients and emphasises the presence of intra-and inter-racial variations of SLE expression including the clinical relevance to autoantibodies.
Echocardiography in systemic lupus erythematosus
Authors: Kalke S , Balakrishanan C , Mangat G , Mittal G , Kumar N , Joshi V R
Published: November 2003

Two dimensional echocardiography with doppler examination was performed in 54 patients with systemic lupus erythematosus (SLE). Nine (17%) had significant cardiac involvement (four left ventricular hypertrophy, one moderate pericardial effusion, one severe aortic regurgitation, and three ventricular systolic dysfunction). We further studied diastolic function in 45 patients who did not have a major abnormality in echo. SLE was graded as active in 16 patients (SLEDAI > 5) and inactive in 29 patients. Twenty age-and sex-matched subjects acted as controls. The data were compared using one way ANOVA test. Patients with active disease had significant diastolic dysfunction compared to inactive patients and controls as indicated by increased peak A (P < 0.01) and decreased E/A ratio (P < 0.01). There was no linear correlation between disease activity and diastolic dysfunction if SLEDAI was considered as a continuous variable (r = 0.29 for E =A). Anticardiolipin antibodies (both IgG and IgM) were elevated in five patients (13 studied). One of them had severe mitral regurgitation, one had trace mitral and aortic regurgitation and one had diastolic dysfunction.

We conclude that asymptomatic diastolic dysfunction is present in SLE patients.
SLE autoantibodies binding to native calf thymus DNA brominated in high salt
Authors: Moinuddin  , Arjumand S , Ali A
Published: November 2003

Native calf thymus DNA was brominated in high salt to achieve B→Z conformational transition. Ultraviolet and circular dichroism spectroscopic studies point towards the conformational modification of the native DNA. Specific binding of the monoclonal anti-Z-DNA antibody (Z- 22) to the DNA brominated in high salt further confirmed the B→Z conformational isomerization of native DNA. The role of Z-DNA in the etiopathogenesis of systemic lupus erythematosus has been investigated in the light of the binding of naturally occurring human anti-DNA autoantibodies to the induced Z-DNA.
Exacerbation of systemic lupus erythematosus related to cytomegalovirus infection
Authors: Hayashi T , Lee S , Ogasawara H , Sekigawa I , Iida N , Tomino Y , Hashimoto H , Hirose S
Published: November 2003

We report two patients with systemic lupus erythematosus (SLE) in whom cytomegalovirus (CMV) infection may have played a significant role in the exacerbation or onset of symptoms. The first patient had thrombocytopenia and the second had proteinuria. CMV infection was observed in both patients when their symptoms developed.
Abnormal pattern of tyrosine phosphorylation in unstimulated peripheral blood T lymphocytes from patients with systemic lupus erythematosus
Authors: Blasini A M , Alonzo E , Chacón R , Riera R , Stekman I L , Rodriguez M A
Published: November 2003

Previous reports have shown abnormal responses mediated via the TCR/CD3 pathway in T lymphocytes from systemic lupus erythematosus (SLE) patients. Recently, we and others have reported augmented TCR/CD3-mediated responses in lupus T cells. It is possible that the pattern of downstream biochemical signals triggered by TCR/CD3 ligation may be altered in T lymphocytes from patients with SLE, thus leading to abnormal distal cell responses. In this paper we have examined the phosphorylation of proteins on tyrosine residues in peripheral blood T lymphocytes from a group of SLE patients and controls. We found a lower frequency of constitutively tyrosine phosphorylated 119-and 113-kDa substrates and an enhanced frequency of tyrosine-phosphorylated 66-and 25-kDa proteins in unstimulated cultures of SLE T lymphocytes, suggesting an altered pattern of tyrosine phosphorylation in T cells from patients in vivo. Additionally, the protein tyrosine phosphatase (PTP) activity of CD45 immunoprecipitates was lower in unstimulated lupus T cells and was enhanced after stimulation via the CD3 pathway in lupus but not control T lymphocytes. The present results seem to suggest abnormal regulation of in-vivo tyrosine phosphorylation in T cells from patients with SLE.
Anticardiolipin antibodies in childhood rheumatic disorders
Authors: Gedalia A , Molina J F , García C O , Doggett S , Espinoza L R , Gharavi A E
Published: November 2003

Anticardiolipin antibodies (aCL) have been reported to occur in a wide variety of autoimmune and non-autoimmune disorders in adults.

Our objective was to investigate the prevalence and isotype distribution of aCL and its relationship with the features of antiphospholipid syndrome (APS) in childhood rheumatic disorders.

Between November 1995 and May 1996, all patients who visited our paediatric rheumatology clinic whose guardians signed a consent form participated in the study. The study population included 106 patients (36 systemic lupus erythematosus (SLE), 28 juvenile rheumatoid arthritis (JRA), 11 fibromyalgia, 7 sarcoidosis, 5 dermatomyositis, 3 rheumatic fever (RF), 3 vasculitis, 2 scleroderma, and 11 miscellaneous). aCL measurements were performed by enzyme linked immunoabsorbent assay (ELISA). All patients were carefully evaluated for symptoms and signs of APS.

Eighteen of the 106 patients (17%) were tested positive for one or more of the three aCL isotypes. In SLE, aCL were found positive in 13 of 36 (37%); in JRA 2 of 28 (7%); in sarcoidosis 2 of 7; and in RF 1 of 3. aCL of IgG isotype were found positive in 16 patients (11 SLE, 2 sarcoidosis, 2 JRA, and 1 RF). This isotype was usually detected at low titers (16–24 GPL). aCL of IgM isotype were found positive in five patients (2 sarcoidosis, 2 SLE, 1 JRA), and aCL of IgA isotype were found positive in only three patients (2 SLE, 1 sarcoidosis). Clinical features of APS were rarely seen in our SLE population and were not associated with the presence of aCL. None of the patients in the other groups exhibited any clinical manifestations of APS.

In conclusion, aCL were found in 37% of our childhood SLE patients as compared with only 7% in JRA. These were mostly aCL of IgG isotype of low titers and therefore were not associated with the main features of APS. Prospective studies with a larger sample size may be needed to ascertain the exact prevalence and clinical significance of aCL in childhood-onset SLE.
Effector and predisposing genes in murine lupus
Authors: Theofilopoulos A N
Published: November 2003

This Publication is No. 11789-IMM from the Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road/IMM3, La Jolla, CA 92037. The work of the author reported herein was supported, in part, by NIH grants AR39555, AR31203, and AG15061.
Cellular interactions in the pathogenesis of lupus nephritis: The role of T cells and macrophages in the amplification of the inflammatory process in the kidney
Authors: Kuroiwa T , Lee E G
Published: November 2003

A significant number of T cells and macrophages infiltrate the kidneys of patients with lupus nephritis. Chemotactic factors, especially monocyte chemoattractant factor-1 (MCP-1) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), cooperatively facilitate recruitment of mononuclear cells into inflamed tissue. Increased expression of class II MHC molecules and CD40 on renal tubular epithelial cells coupled with upregulation of CD40 ligand (CD40L) and interleukin-2 receptor on infiltrating T cells suggest ongoing cellular immune responses. Recent studies employing knockout mice suggest that the TH-1 cytokine interferon-γ is an important cytokine in amplifying the local immune response of lupus nephritis. Infiltrating mononuclear cells exert their effects on resident renal cells through secretion of soluble factors and/or direct cell to cell contact. These interactions, among others, involve molecules such as CD40=CD40L and adhesion molecules. Studies to better define these molecules are in progress and may provide additional targets for therapeutic intervention. Thus, while autoantibody production and complement activation are the major players in initiating the inflammatory response in lupus nephritis, cellular immune mechanisms mediated through infiltrating mononuclear cells have an important role in its amplification and the progression of renal injury.
Mechanisms of progression of renal damage in lupus nephritis:Pathogenesis of renal scarring
Authors: Grande J P
Published: November 2003

Lupus nephritis results from an acute inflammatory and immunological response to renal immune complex deposition. The acute response is characterized by activation of circulating leukocytes and renal parenchymal cells, triggering the production of pro-inflammatory cytokines and growth factors. In all too many cases, this response is followed by a chronic response, which is characterized by excessive deposition of collagen and other extracellular matrix macromolecules and the development of end-stage renal disease. Mechanisms underlying this chronic response in progressive renal disease are not adequately defined. In this overview, potential roles of reactive oxygen species (ROS) generation and transforming growth factor-β (TGF-β) production in the pathogenesis of lupus nephritis are considered. ROS and TGF-β may be key elements of a pathway leading to persistent and excessive matrix deposition in progressive lupus nephritis. Further studies to define the role of this pathway in lupus nephritis may lead to the development of additional, more specific therapeutic targets to prevent progression of renal disease.
Renal biopsy in lupus nephritis
Authors: Grande J P , Balow J E
Published: November 2003

Renal biopsy can be extremely valuable in the management of patients with lupus nephritis. It is remarkably common to find pathological evidence of substantial nephron loss in patients with low grade laboratory abnormalities. This is due to compensatory hypertrophy and hemodynamic adjustments within the less diseased nephron mass. It has been shown that the decision to institute immunosuppressive therapy is highly informed by the results of renal biopsy and offers the prospect of achieving more favorable renal outcomes. Kidney biopsies should be evaluated by dedicated renal pathology services experienced in diagnostic light, immunofluorescence and electron microscopy. Biopsies should be classified according to the World Health Organization (WHO) system and specific lesions semiquantitatively scored against a checklist of features comprising activity (reversible) and chronicity (irreversible damage) indices. The renal biopsy findings should be reviewed jointly by pathologists and the clinicians caring for patients with lupus nephritis.
Outcome criteria for lupus nephritis trials: A critical overview
Authors: Boumpas D T , Balow J E
Published: November 2003

Lupus nephritis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus. Traditional outcome criteria such as doubling of serum creatinine, end stage renal disease and death have been used in controlled therapeutic trials, but are limited by their low incidence and the extended period of time required to reach them. More recently, discussions have focused on composite outcome measures, such as remission and relapse, as well as measures of health related quality of life, general lupus activity and cumulative damage indexes. We review the strengths and weaknesses of several outcome criteria, and we propose criteria for both small pilot studies and large definitive trials.
Flares in lupus nephritis: Incidence, impact on renal survival and management
Authors: Ponticelli C , Moroni G
Published: November 2003

One of the characteristics of systemic lupus erythematosus (SLE) is the large inter-and intra-individual variability of the clinical course. Lupus nephritis is no exception. Some patients with kidney involvement may show rapid progression to renal failure, others may enter complete and stable remission after adequate therapy while a number of other patients, with similar clinical and histological pattern at presentation, may alternate periods of clinical quiescence with renal exacerbations of different severity. In this paper we focus on the incidence, the prognostic significance and the treatment of renal flares in patients with SLE nephritis.
Novel approaches in the treatment of lupus nephritis
Authors: Illei G G , Klippel J H
Published: November 2003

Lupus nephritis can be managed successfully in the majority of cases; most therapies, however, are associated with significant side-effects. Several new agents aiming at specific stages in the pathogenesis of lupus are in different phases of clinical trials. The central role of lymphocytes makes them targets of various therapeutic approaches. Lymphocyte depletion can be achieved by high-dose chemotherapy with or without bone marrow transplantation. Nucleoside analogs selectively deplete mononuclear cells; antibodies against T or B cell surface antigens target specific subsets of lymphocytes. Synchronized plasmapheresis has been used in an attempt to delete pathogenic lymphocyte clones activated by plasmapheresis. Treating patients with DNase or neutralizing pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiotype antibodies may prevent immune complex formation and/or deposition. Blocking the complement cascade or some of the inflammatory mediators like thromboxane A2 may be efficacious even if immune complex deposition could not be prevented. Inducing antigen-specific tolerance or interfering with important interactions between T-lymphocytes and other cells by blocking CD40 ligand or decreasing the level of interleukin-10 are some of the other approaches currently under clinical investigation.
End-stage renal disease in lupus: Disease activity, dialysis, and the outcome of transplantation
Authors: Stone John H
Published: November 2003

Lupus nephritis remains a major cause of morbidity in SLE. Approximately 10% of patients with SLE develop end-stage renal disease (ESRD). In most SLE patients, disease activity diminishes as ESRD approaches. Consequently, the survival of SLE patients on dialysis (both hemo-and peritoneal) appears to be comparable to that of non-SLE patients. However, the role of anti-phospholipid (aPL) antibodies in causing dialysis-related morbidity among patients with SLE requires further investigation. In contrast to the outcomes of dialysis, recent evidence suggests that renal transplantation outcomes among SLE patients are inferior to those of non-SLE patients, primarily because of the risk of recurrent lupus nephritis in the allograft and the effect of aPL-related events on transplantation outcomes. Future avenues of investigation should be directed at developing better strategies to manage and prevent these complications.
The interdisciplinary team's approach to lupus nephritis
Authors: Crane M , Pucino F , Sebring N , Irby D , Perry M , Mattiko M , Yarboro C
Published: November 2003

The interdisciplinary team approach in assessment and treatment of patients with chronic disease in general and lupus nephritis in particular provides a global format for identifying the multiple problem areas that retard or prevent optimal patient functioning. These areas include the physical, emotional, economic, psychosocial, and functional. Benefits to the individual patient include a thorough multifaceted assessment by professionals who have the benefit of peer collaboration and validation. This increases the likelihood that the whole patient is considered, not just the problem of nephritis. For example, how does the patient and her or his family cope with the impact of such a disease and how, in turn, do the coping abilities of the patient and family affect the disease. The interdisciplinary team also assesses how the treatment strategies for each problem area influence each other. Finally, the interdisciplinary team serves as a positive role model for effective collaboration among health professionals and for students in their respective disciplines.
Affinity purified human antiphospholipid antibodies bind normal term placenta
Authors: Donohoe S , Kingdom J C P , Mackie I J
Published: November 2003

Antiphospholipid antibodies (aPL) are associated with an increased incidence of fetal loss, but the pathophysiology remains unclear. One mechanism may involve the binding of aPL directly to the placenta where they may initiate placental thrombosis and infarction. We have developed an immunofiuorescent technique to detect human aPL binding to human placenta. Endogenous immunoglobulins were eluted by extensive washing and residual staining was prevented by incorporating multiple blocking steps. APL were affinity purified on both cardiolipin and phosphatidylserine liposomes from the sera of six patients with aPL (five antiphospholipid syndrome (APS) patients and one post bone marrow transplant patient). Heterogeneous binding to normal term placenta, involving either the trophoblast microvillous surface, stromal and perivascular regions was demonstrated by affinity purified aPL from five of six patients. Preliminary sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting studies have demonstrated that aPL bind a number of placental proteins. b2GPI was not the predominant protein bound by aPL using this technique. This study provides further evidence for the involvement of aPL in mediating placental damage.
Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas expression, serum soluble Fas and disease activity
Authors: Courtney P A , Crockard A D , Williamson K , McConnell J , Kennedy R J , Bell A L
Published: November 2003

Lupus specific autoantigens are exposed on apoptotic cells. The increased number of apoptotic lymphocytes reported in systemic lupus erythematosus (SLE) may be attributable to abnormalities of lymphocyte Fas expression or serum soluble Fas.

In the present study we analysed the count of circulating apoptotic lymphocytes in SLE patients (n ‘ 50), by flow cytometry using Annexin V, compared to rheumatoid arthritis patients (RA, n ‘ 20), inflammatory bowel disease patients (IBD, n ‘ 20) and normal controls (n ‘ 20). Lymphocyte Fas expression and serum soluble Fas were measured and related to numbers of apoptotic lymphocytes.

The percentage of apoptotic lymphocytes, determined by Annexin V binding, was significantly increased in peripheral blood of SLE patients (median ‘ 4.2%) compared with normal healthy donors (median ‘ 1.1%) and IBD patients (median ‘ 2.0%) but not RA (median ‘ 3.9%). SLE lymphocyte Fas expression was not significantly different from RA or IBD patients. Serum soluble Fas in SLE patients correlated positively with apoptotic lymphocytes and antibodies to double stranded DNA.

This study suggests that increased apoptotic lymphocytes and increased lymphocyte Fas expression may not be specific to SLE. Serum soluble Fas may have a role in the regulation of lymphocyte apoptosis in SLE.
Clinical and laboratory features of patients of Vietnamese descent with systemic lupus erythematosus
Authors: Phan J C , Bush T M , Donald F , Ward M
Published: November 2003

The prevalence rate and disease manifestations of systemic lupus erythematosus (SLE) have been noted to vary among different ethnic groups. There has been no description in the English literature of SLE in the Vietnamese population. This is the first report, which details the clinical and laboratory features as well as an estimation of the prevalence of SLE in patients with a Vietnamese ancestry living in the United States.

We performed a retrospective chart review of clinical and laboratory features of patients of Vietnamese descent with SLE. The case finding was performed by a review of the rheumatology clinic records at two large teaching hospitals in Santa Clara County searching for patients with SLE with a Vietnamese surname. In addition, we recruited patients by contacting all of the rheumatologists practicing in the county.

Twenty-three patients of Vietnamese descent were identified with SLE in Santa Clara County. The estimated prevalence of SLE in the patients of Vietnamese descent was 42 cases per 100 000 persons. Eighty-seven per cent of the cases were born in Vietnam. The clinical and laboratory features of SLE were similar to prior published reviews except for a relatively high prevalence of anti-RNP antibody (54%). The patients with anti-RNP antibody exhibited features of overlap syndrome. There was a high rate of exposure to tuberculosis (TB). Fifty-eight per cent of patients had a positive purified protein derivative (PPD) skin test and 27% of patients had a history of clinical TB. Forty-four per cent of patients had evidence of hepatitis B exposure.

The prevalence of SLE in the Vietnamese population in Santa Clara County is similar to that of other Asian populations. There was a relatively high prevalence of anti-RNP antibody in our patient group which was associated with overlap features. As expected in an immigrant population from Southeast Asia, there was a high rate of prior exposure to tuberculosis and hepatitis B. Clinicians should diligently screen for these infections and appropriately prophylaxe and treat patients.
Systemic lupus erythematosus (SLE) and hair treatment: a large community based case-control study
Authors: Hardy C J , Palmer B P , Muir K R , Powell R J
Published: November 2003

Objective: To investigate the association of hair treatment, including permanent and non-permanent dyes, bleach, highlights and lowlights on the development of systemic lupus erythematosus (SLE).

Methods: 150 SLE patients and 300 controls from Nottingham, UK were interviewed in a casecontrol study. Controls were matched to cases for gender and year of birth. All patients met at least four of the American Rheumatology Association criteria for SLE. Controls were randomly selected from the Nottingham Family Health Services Authority register. Information was collected via an interview-administered questionnaire concerning demographic variables and hair treatment.

Results: For hair treatment no significant associations were observed between ever using permanent colouring, non-permanent colouring, bleach or lowlights, and disease. Nevertheless a significant association (OR 0.55, 95% CI 0.31–0.95) was observed between ‘ever having’ used highlights and disease with cases having used highlights less frequently than their healthy counterparts. No significant differences were observed in duration of usage of hair bleach, permanent colouring, non-permanent colouring, highlights and lowlights between cases and controls.

Conclusions: Hair treatment or duration of hair treatment usage is not significant in the aetiology of SLE. Although patients with SLE were less likely in this study to have highlights than controls, for all other hair treatments no differences were observed.
Intra-uterine death due to umbilical cord thrombosis secondary to antiphospholipid syndrome
Authors: Brewster J A , Quenby S M , Alfirevic Z
Published: November 2003

This is a case of intra-uterine death due to a thrombotic event on the fetal side of circulation in a woman who was subsequently diagnosed with Antiphospholipid Syndrome.
Risk factors for hypercreatinemia in patients with systemic lupus erythematosus
Authors: Rzany B , Coresh J , Whelton P K , Petri M
Published: November 2003

Renal insufficiency is one of the most severe outcomes of systemic lupus erythematosus (SLE). The aim of this study was to identify baseline predictors of the development of renal insufficiency in a cohort of patients with SLE. 281 patients from the The Hopkins Lupus Cohort (HLC) enrolled between 1987–1994 were followed for the occurrence of renal insufficiency, defined as a serum creatinine 1.6 mg/dl for men and 1.4 mg/dl for women.

Over a mean (±s.d.) of 3.3±2.1 y of follow up, 46 (16%) of the 281 patients developed renal insufficiency. Using a multivariate Cox proportional hazard model, we found the risk of renal insufficiency associated with younger (0–19 y) or older (40 y) age at baseline (relative risk (95% CI) 5.1 (1.4, 18.8) and 4.1 (2.1, 8.2)) and longer duration of SLE before referral to the cohort (RR 1.25 [1.05, 1.5] for every five years). Additional predictive variables were borderline elevation of serum creatinine at baseline (RR 3.1 (1.4, 6.6) for a serum creatinine 1.4–1.5 mg/dl for men and 1.2–1.3 mg/dl for women), and mean proteinuria (RR 3.6 (1.8, 7.4) for trace–3 + and 10.6 (3.8, 30.0) for 3 + (urine dipstick level)). Socioeconomic status, race, autoantibodies and complement were not significantly associated with the risk of renal insufficiency.

This study supports early referral of SLE patients to rheumatologists and emphasizes the importance of early signs of renal involvement as predictors of later renal insufficiency in SLE patients.
Lupus anticoagulant–hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature
Authors: Erkan D , Bateman H , Lockshin M D
Published: November 2003

We describe two patients whose initial presentation of systemic lupus erythematosus (SLE) was accompanied by haemorrhagic episodes and significant coagulopathy. Further investigation demonstrated positive lupus anticoagulant and decreased Factor II (prothrombin) activity. Both patients were diagnosed with lupus anticoagulant–hypoprothrombinemia syndrome (LAC–HPS) as a result of non-neutralizing antibodies directed against Factor II. LAC–HPS is a rare clinical entity that can occur in association with SLE, transient viral infections, drug reactions or even in healthy individuals. Mixing studies, which can be affected by other coagulation factor inhibitors, play an important role in the diagnosis of LAC–HPS. Factor VII level was decreased in the second patient, a finding that has not previously been reported in association with SLE. In both patients, bleeding stopped promptly and coagulation studies improved significantly with high dose corticosteroids. We discuss the pathogenesis, diagnosis and management of LAC–HPS in patients with SLE.
Immunisation of patients with systemic lupus erythematosus: the current state of play
Authors: Ioannou Yiannis , Isenberg David A
Published: November 2003

Concerns regarding the safety and efficacy of immunisation in patients with SLE have persisted for over 50 y and indeed infection remains a leading cause of morbidity and mortality in these patients. There have been many anecdotal reports in the literature linking vaccination with either induction or exacerbation of SLE disease. However prospective studies have shown that immunisation with inactivated/killed vaccines is probably safe in patients with SLE. Individuals on immunosuppressive agents and/or high dose steroid (more than 20 mg/d) should not receive live vaccines, as stated in guidelines proposed by the British Society of Rheumatology. The safety of hepatitis B vaccination in patients with SLE is as yet undetermined and a prospective study is required. However until such evidence becomes available the advice of the BSR should be followed and patients with SLE who are at risk of exposure should be vaccinated.

It remains uncertain whether the immune response to immunisation is significantly impaired by active disease and/or immunosuppressive treatment and to what extent. Most patients do however seem to mount a satisfactory immune response though this may not be quantitatively and qualitatively the same as healthy controls.
Neonatal lupus erythematosus: analysis of HLA class I genes in Japanese child/mother pairs
Authors: Miyagawa S , Kidoguchi K , Kaneshige T , Shirai T
Published: November 2003

Neonatal lupus erythematosus (NLE), characterized by two major symptoms of congenital heart block (CHB) and transient cutaneous lesions, is an antibody mediated disorder due to placentally transmitted maternal autoantibodies to Ro/SSA and/or La/SSB. We genotyped 14 mothers, 9 children with CHB, 8 with cutaneous NLE only and 5 asymptomatic siblings at HLA class I loci, by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with sequence-specific amplification. Mothers of children with NLE exhibited a very high polymorphism of HLA class I genes. Significant increases of HLA-B*1501 (B62) and Cw*0303 (Cw9) with absence of HLA-Al/B8 haplotype in Japanese mothers differed from the serologically defined HLA class I profiles among NLE mothers in white and North American black populations. Child/mother heterozygous HLA-A/B/C haplotype identity, which extended to HLA-class II DR/DQ loci, was observed in only one of 9 cases with CHB. No association was found between HLA class I alleles of children and the symptoms of NLE. These findings provide for the opportunity to investigate the primary genetic associations with NLE/CHB in different ethnic groups.