bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE
Authors: Podrebarac T A , Boisert D M , Goldstein R 
Published: November 2003

Objective: To investigate the predisposing role of major histocompatibility complex (MHC) genes to autoantibody production and clinical manifestations comparing French Canadian and Non-French Canadian Caucasians with systemic lupus erythematosus (SLE) Methods: Ninety-one Caucasian patients with SLE were studied. Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing) were determined. Results: Photosensitivity was present in all SLE subjects with anti-Ro antibodies (P = 0.001, RR = 13.1, Cl = 1.8, 564). Photosensitivity was further associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A gene deletion was associated with anti-Ro (P = 0.008, RR = 4.6, Cl = 1.4, 16.2) and anti-La (P = 0.02, RR = 11.7, Cl = 1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P = 0.01, RR = 21.3, Cl = 1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P = 0.02, RR = 0.3, Cl = 0.07, 0.8) and correlated with HLA-DR15 (P = 0.006, RR = 4.2, Cl = 1.5, 12.8) and Dw2 (P = 0.009, RR = 3.9, Cl = 1.4, 11.9). Conclusion: C4A gene deletion has a previously unrecognized powerful association with anti-Ro and anti-La autoantibodies. These results support the concept of divergent MHC gene associations with autoantibody expression and emphasize the influence of ethnicity on the immunogenetic study of SLE.
Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus
Authors: Reifen R , Blank M , Afek A , Kopilowiz Y , Sklan D , Gershwin M E , German B , Yoshida S , Shoenfeld Y 
Published: November 2003

Objective: To examine the effect of diets with different polyunsaturated fatty acid contents, including linseed oil which contains 70% omega-3 fatty acids, on autoantibody production in idiotype induced mouse model of systemic lupus erythematosus (SLE). Methods: Five different fats were fed to mice with induced SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and histological examination of kidneys were carried out. Results: SLE mice fed linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less severe kidney damage than mice fed other diets, including fish oil. Conclusion: Use of linseed oil may attenuate the severity of SLE and this diet may be recommended for other auto-immune diseases as well.
Systemic lupus erythematosus VII: frequency and impact of secondary Sjøgren's syndrome
Authors: Nossent J C , Swaak A JG 
Published: November 2003

Background: The prognosis of patients with systemic lupus erythematosus (SLE) largely depends on the severity of cumulative organ damage during the course of the disease. While Sjùgren's syndrome (SS) predominantly affects exocrine glands, a considerable number of patients develop visceral organ damage. Thus, the occurrence of a secondary SS (2°SS) in SLE patients, may result in more extensive organ damage and thereby adversely affect prognosis. Patients/Methods: 138 patients meeting the 1982 American College of Rheumatology (ACR) classification criteria for SLE were prospectively studied over a mean period of ninety months. 2°SS was diagnosed according to the 1993 European Study Group criteria and complication rates and prognosis were compared between patients with and without SS. Results: 27 patients (19%) developed SS after a mean period of 48 months. There was a gradual increase in SS prevalence over time after SLE-onset. 2°SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and similar serological profiles (including anti-SSa) as patients without SS. Overall mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable analysis showed improved survival estimates for 2°SS patients with borderline statistical significance (P = 0.06). Conclusions:2SS develops in about one-fifth of SLE patients in a time-dependent fashion: these patients are older, have less renal involvement and their prognosis is at least as good as for those remaining free of SS.
Polyarteritis nodosa, microscopic polyangiitis and Churg–Strauss syndrome
Authors: Lhote F , Cohen P , Guillevin L 
Published: November 2003

Polyarteritis nodosa (PAN), first described by Küssmaul and Maier, is a well-known form of necrotizing angiitis whose manifestations are weight loss, fever, asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous manifestations, hypertension, gastrointestinal tract involvement, and cardiac failure. Recently individualized from PAN, microscopic polyangiitis (MPA) is a systemic vasculitis of small-size vessels whose clinical manifestations are very similar to those of PAN, but it is characterized by the presence of rapidly progressive glomerulonephritis (RPGN), which is nearly constant, and pulmonary involvement usually absent in PAN. Churg–Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systemic vasculitis similar to that of PAN and occurring in individuals with asthma and allergic rhinitis. Considering the etiologies of PAN, primary and secondary vasculitides can also be distinguished because PAN can be the consequence of hepatitis B virus (HBV) infection and sometimes of other etiologic agents. The prognosis of systemic vasculitides has been transformed by corticosteroids that are, except in HBV-related PAN, the basic treatment. Immunosuppressive drugs, especially cyclophophamide, have also contributed to improving the prognosis, but their precise role in the management of these vasculitides is still being elucidated.
Platelet activation and turnover in the primary antiphospholipid syndrome
Authors: Joseph J E , Donohoe S , Harrison P , Mackie I J , Machin S J 
Published: November 2003

Thromboembolism is a common occurrence in patients with the antiphospholipid syndrome (APS). The mechanism responsible for this phenomenon is unclear; there are several theories. One possibility is that a pathogenic interaction exists between antiphospholipid antibodies and platelets, leading to their activation. This study examined the expression of the platelet activation markers CD62 and CD63 by flow cytometry in 20 patients with the primary antiphospholipid syndrome (PAPS). Levels of soluble P-selectin were also assayed. Reticulated platelets were measured as an indicator of increased platelet production and/or turnover. Median CD63 expression was significantly increased in patients (14.3%) compared to a group of healthy controls (10.1%, P , 0.0008). There was no significant difference in median CD62 expression or percent reticulated platelets between the two groups. The median level of soluble P-selectin was significantly higher in PAPS patients (35.5 ng/ml) compared to controls (18.8 ng/ml, P , 0.0028). Patients receiving aspirin had lower median CD63 values (13.1%) when compared to those patients who were not (18.0%, P , 0.023). However, aspirin therapy did not prevent significant platelet activation occurring in some individual patients. Our data suggest that although not excessive, there is a degree of increased platelet activation in some PAPS patients, which is not always suppressed by antiplatelet therapy with aspirin.
Defective early T and T-dependent B cell activation in systemic lupus erythematosus
Authors: Fernández-Gutiérrez B , de Miguel S , Morado C , Hernández-García C , Bañares A , Jover J A 
Published: November 2003

Systemic lupus erythematosus (SLE) is characterized by autoantibody production of unknown origin. Since T-B cell interaction is a key event to produce antibodies, we investigated this interaction through study of CD69, CD40 ligand (CD40L) and CD23 expression (three very early activation antigens). Peripheral blood mononuclear cells (PBMC) from inactive lupus patients were studied following culture with either medium alone, anti-CD3 monoclonal antibody (mAb), recombinant interleukin-4 (rIL-4) or phorbol myristate acetate (PMA)–ionomycin. Analysis of CD23 expression on lupus B cells in basal conditions and after anti-CD3 challenge of PBMC, a reflection of cognate interaction between T and B cells, was clearly defective. Conversely, CD23 expression on lupus B cells following non-cognate T cell signals (rIL-4) was preserved. CD69 and CD40L expression was also impaired in lupus T cells following anti-CD3 challenge. Nonetheless, activation by means of PMA and/or ionomycin was preserved both in T cells (CD69 and CD40L expression) and in B cells (CD23 expression). These results indicate that B cells from inactive lupus patients display a normal early response to direct B-cell stimuli. Conversely, T-dependent B-cell stimuli are clearly defective in SLE patients in remission. These results indicate that T-B cognate interaction related to defective T cell activation located between surface membrane and protein kinase C (PKC)=ionomycin function is an intrinsic characteristic of these patients.
Immunomodulation of murine experimental SLE-like disease by interferon-γ
Authors: Amital H , Levi Y , Blank M , Barak V , Langevitz P , Afek A , Nicoletti F , Kopolovic J , Gilburd B , Meroni P L , Shoenfeld Y 
Published: November 2003

The objective of this study was to assess the impact of murine recombinant IFN-γ and anti-IFN-γ monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16=6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-γ, anti-IFN-γ mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-γ intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-γ treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-γ treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-γ treated mice. IFN-γ upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-γ administration can aggravate the clinical and laboratory outcome of 16=6id induced lupus in BALB/c mice.
Apoptosis and expression of soluble Fas mRNA in systemic lupus erythematosus
Authors: Papo T , Parizot C , Ortova M , Piette J-C , Frances C , Debre P , Godeau P , Gorochov G 
Published: November 2003

Our objective was to measure the relative proportions of messenger RNAs coding for soluble and membrane-bound Fas in peripheral blood mononuclear cells (PBMCs) and to quantify lymphocyte apoptosis in vitro in systemic lupus erythematosus (SLE). A RT-PCR (soluble/membrane Fas mRNA) ratio was calculated in 16 SLE, 11 RA and 16 healthy subjects' PBMCs. Apoptosis was quantitated in vitro using nick-end labeling and flowcytometry analysis immediately and after overnight T cell activation. The mean soluble/membrane Fas ratio was 1.219–0.424 in the SLE group, significantly higher than in healthy subjects, 0.516–0.180 (P = 0.0001). There was no significant difference between inactive and active SLE groups whereas Fas ratio was higher in SLE patients with nephritis (1.460–0.365) compared to those without nephritis (1.031–0.380) (P = 0.039). Mean soluble/membrane Fas ratio in RA patients (0.975–0.37) was higher than in healthy subjects (P = 0.0003) and lower than lupus nephritis patients (P = 0.015). A significantly higher proportion of mononuclear cells engaged apoptosis after T cell activation in active lupus patients, compared to control subjects. In comparison with healthy subjects, Fas alternative splicing was skewed toward the soluble form of Fas in SLE and RA. Apoptosis after T cell activation in vitro was increased in active SLE patients.
Identification and characterization of a calreticulin-binding nuclear protein as histone (H1), an autoantigen in systemic lupus erythematosus
Authors: Treves S , Bajocchi G , Zorzato F , Govoni M , Trotta F 
Published: November 2003

Our objective was to identify nuclear calreticulin-binding protein(s) and investigate whether there is a correlation between presence of autoantibodies against calreticulin and calreticulin-binding protein(s) in the sera of patients suffering from systemic lupus erythematosus (SLE). The ligand overlay procedure using digoxigenin-labelled calreticulin was used to identify a calreticulin-binding protein in the nuclear fraction of bovine brain. Fractionation of the nuclear components was used to localize the major positive calreticulin-binding protein. The protein was partially purified using hydroxylapatitie chromatography and subjected to NH2-amino acid sequence analysis. Immunoblots using the sera of SLE patients were then carried out on calreticulin and the calreticulin-binding protein. The calreticulin-binding protein present in the nucleoplasm was identified as histone H1. Approximately 62% (26=42) patients with SLE had IgG antibodies directed against H1 whereas the sera of healthy individuals did not react with the antigen; 36% of patients with SLE had both anticalreticulin and anti-histone H1 antibodies. Phosphorylation of the latter protein did not alter its immunoreactivity. These findings demonstrate that the concomitant presence of autoantibodies directed against both calreticulin and histone H1 occurs frequently in patients with SLE and may help shed some light on the mechanisms which bring about the autoimmune response.
Association of an insertion polymorphism of angiotensinconverting enzyme gene with the activity of systemic lupus erythematosus
Authors: Sato H , Akai Y , Iwano M , Kurumatani N , Kurioka H , Kubo A , Yamaguchi T , Fujimoto T , Dohi K 
Published: November 2003

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65 IU/ml (4.05, 6.8)) (P < 0.01). Moreover, patients with the II genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.
Genetic susceptibility to lupus nephritis
Authors: Tsao B P 
Published: November 2003

Although cumulative evidence suggests that a genetic predisposition plays a major role in development of systemic lupus erythematosus (SLE) and/or lupus nephritis (LN), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to multiple genes with variable genetic effects and the diverse genetic backgrounds of human populations. In human SLE, genes of early components of complements as well as many polymorphic genes (including the MHC class II and class III, FcγR, mannose-binding protein, IL-6, Bcl-2, and IL-10 genes) have been associated with SLE or LN by population-based case-control or within-case studies. The contribution of some of these disease-associated genes to the presence or absence of clinical manifestations has been further tested in mice with targeted disruption of the specific candidate gene. In addition to SLE susceptibility genes, there may be a separate set of nephropathy susceptibility genes predisposing to LN as suggested by the familial clustering of endstage renal disease in African-Americans with LN. The availability of densely mapped genetic markers spanning the entire genome has enabled the identification of chromosomal regions linked to disease susceptibility genes without prior knowledge of the gene function. Our group has used known murine lupus susceptibility loci as a guide, and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sib pairs from multiple ethnic groups. More recently, several groups have reported results of genome scans of SLE-affected sib pairs or pedigrees. These exciting recent developments in delineating the genetic basis of SLE or LN are summarized in this review.
Lupus nephritis in children
Authors: Gloor J M 
Published: November 2003

The renal manifestations of systemic lupus erythematosus in childhood range from minor abnormalities detected on urinalysis to severe renal insufficiency requiring renal replacement therapy. Clinically significant renal involvement in systemic lupus erythematosus is more common in children than in adults. Effective treatment for childhood lupus nephritis is available, and the prognosis for affected children has improved over the course of the last 30 years. Corticosteroid therapy remains the cornerstone of treatment for children with lupus nephritis. The addition of cytotoxic agents to corticosteroid treatment improves both the long and short-term prognoses. Cyclosporin may improve the clinical manifestations of lupus nephritis although the disease remains active serologically. Although survival in childhood lupus has improved, complications of therapy result in significant morbidity with distressing frequency. Immunosuppression may result in mortality and morbidity due to opportunistic infections. Individuals with otherwise successful control of renal manifestations of systemic lupus erythematosus may still be left with significant morbidity due to disturbances in growth due to long-term corticosteroid treatment. Psychosocial development may be adversely affected both as a result of chronic illness as well as due to the effects of therapy. Meticulous attention to detail over decades of treatment is necessary to optimize patient outcome in childhood lupus nephritis.
Validation of the medical outcomes study family and marital functioning measures in SLE patients in Singapore
Authors: Thumboo J , Fong K-Y , Chan S-P , Leong K-H , Feng P-H , Thio S-T , Boey M-L 
Published: November 2003

Objective: To validate the Medical Outcomes Study Family and Marital Functioning Measures (FMM and MFM) in a multi-ethnic, urban Asian population in Singapore. Methods: English speaking Chinese, Malay or Indian SLE patients (n ‘ 120) completed a selfadministered questionnaire containing the FFM and MFM at baseline, after 2 weeks and after 6 months. Lupus activity, disease-related damage and quality of life were assessed using the British Isles Lupus Assessment Group (BILAG), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and SF-36 Health Survey respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's a, quantifying test-retest differences and known-groups construct validity. Results: Factor analysis of scores obtained at baseline and after 6 months identified 3 factors corresponding to the FFM (1 factor) and the MFM (2 factors). Both scales showed acceptable internal consistency, with Cronbach's a of 0.95 for the FFM and 0.70 for the MFM. Mean (s.d.) test-retest differences were 7 0.31 (3.82) points for the FFM and 7 0.70 (4.26) points for the MFM. Eleven out of 13 a priori hypotheses relating both the FFM and MFM to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. Conclusion: The FFM and MFM are valid and reliable measures of family and marital functioning in a multi-ethnic cohort of Asian SLE patients in Singapore.
Increased endothelial cell expression of a3β1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome
Authors: Afek A , Shoenfeld Y , Manor R , Goldberg I , Ziporen L , George J , Polak-Charcon S , Amigo M C , Garcia-Torres R , Segal R , Kopolovic J 
Published: November 2003

The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls. One group included seven normal valves from patients who died from non-cardiac diseases. The other group of valves were obtained from patients with bacterial endocarditis during autopsies or valve replacement operations. Immunoperoxidase and immunofluorescence stainings with antibodies to human immunoglobulins, endothelial cells, a3β1 integrin, collagen IV, laminin and fibronectin were employed. Three histopathological patterns were apparent: normal valves, valves with verrucous endocarditis and valves with fibrocalcific changes. In all the valves with verrucous endocarditis the following findings were observed: (1) increased expression of the a3β1 integrin on the endothelial cells, (2) increased amount of collagen IV, laminin and fibronectin, (3) proliferation of blood vessels and (4) linear subendothelial deposition of immunoglobulins and complement. The valves with fibrocalcific changes were deformed and showed a thick layer of collagen IV, laminin and fibronectin, yet in two valves the indothelial cells showed an expression of the a3β1 integrin. The control valves did not express the integrin and had only a thin subendothelial band of collagen IV. In valves from patients with APS,1 markers of endothelial cell activation are upregulated while the inflammatory exudate is scant. There is also a prominent deposition of immunoglobulins in the valves from patients with APS, suggesting a possible association between the deposition of the antibodies and the activation of the endothelial cells in APS.