Biomedical subjects

G Sturfelt

Publications and source records attributed to G Sturfelt.

At least 37 records · Page 2Linked to original sources

PubMed2004

EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.

OBJECTIVE: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE). METHODS: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing. RESULTS: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group. CONCLUSIONS: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.

Administration, Oral↗

PubMed2004

ACR classification criteria for systemic lupus erythematosus: complement components.

Complement is involved in the pathogenesis of systemic lupus erythematosus (SLE) and has also a seemingly paradoxical protective role in the development of the disease. Low levels of components within the classical pathway of complement especially C1q, C4 and C3 have a high specificity for SLE diagnosis and should be considered as promising for inclusion in classification criteria of SLE.

Biomarkers↗

PubMed2004

Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus.

There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.

Age Factors↗

PubMed2004

Outcome of incomplete systemic lupus erythematosus after 10 years.

The objective was to identify cases of incomplete systemic lupus erythematosus (SLE) within a defined population in southern Sweden, risk factors for development of complete SLE (> or = 4 classification criteria) and study outcome of the patients. During prospective retrieval of SLE cases within a defined population in southern Sweden, 28 patients (26 women, two men) with incomplete SLE (< 4 ACR criteria) were identified between 1981 and 1992. All patient records were reviewed and clinical and laboratory data were extracted from standardized formats. Organ damage was defined according to the SLICC/ACR damage index. During follow-ups, 16 of 28 patients developed complete SLE (median 13 years; range 10-20 years). The time to develop complete SLE varied between one and ten years with a median time of 5.3 years. Three patients were anti-DNA positive at inclusion; only one of them developed complete SLE. False positive Wasserman reaction and anti-cardiolipin antibodies (aCl) were only found in patients who developed complete SLE (P < 0.04; Fisher exact test). Six patients had malar rash from the start and they all had complete SLE at follow-up (P < 0.04; Fisher exact test). Of eight patients with arthritis, three developed complete SLE. Thrombocytopenia was only found in two patients, both developing complete disease. At follow-up, patients that developed complete SLE had high SLICC damage scores (mean 1.5) compared with patients that remained as incomplete SLE (mean 0.16). In conclusion, in this follow-up study of patients with incomplete SLE 57% developed complete disease after a median time of 5.3 years. Malar rash and aCl were predictors of complete SLE. Individuals that developed complete SLE were more prone to organ damage.

Adolescent↗

PubMed2003

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗

PubMed2003

The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles.

The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.

Adolescent↗

PubMed2003

The ACR nomenclature for CNS lupus revisited.

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of peripheral and central nervous system manifestations. These manifestations are complex and their pathophysiology is poorly understood. NPSLE can precede the onset of lupus or occur at any time during its course. The American College of Rheumatology (ACR) developed a standardized nomenclature system providing case definitions for the neuropsychiatric syndromes of systemic lupus erythematosus (SLE) to facilitate and enhance patient classification and reporting requirements in clinical research. Estimates of NPSLE prevalence have ranged widely and most are based on research conducted before the introduction of ACR case definitions. This paper reviews the early experience with the ACR nomenclature use and possible future directions for its improvement. The identification and categorization of the major neuropsychiatric syndromes in SLE using ACR case definitions seems to be adequate, however the mildest and most subjective of the syndromes are the most problematic. Even if the definitions in their present form might have drawbacks the only way forward is further use of ACR nomenclature, pooling data from different populations, and collection of experience as a basis for improvement. The acquisition of normative data for ethnic, age and sex stratification would extend their usefulness.

Female↗

PubMed2002

Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality.

OBJECTIVE: To investigate the outcome of neuropsychiatric involvement in systemic lupus erythematosus patients (NPSLE) recruited from a defined population. METHODS: All cases of adult SLE diagnosed during 1981-1995 within the Lund-Orup Health Care District were followed prospectively and neuropsychiatric manifestations were recorded. The SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index, mortality and working incapacity were recorded as measures of outcome. RESULTS: NPSLE manifestations developed in 38% (44/117) of the patients. A high rate of organ damage (SLICC/ACR Damage Index) was recorded in the NPSLE patients (P<0.001). Compared with patients without neuropsychiatric involvement, NPSLE patients were treated more intensively, with glucocorticoids (P<0.01) and cytostatic drugs (P<0.01). When compared with the normal population in the same area, the NPSLE patients had a higher rate of working incapacity (relative risk 4.0, 95% confidence interval 2.06-6.96), whereas mortality was not increased (standardized mortality rate 1.4, 95% confidence interval 0.5-3.0). CONCLUSIONS: SLE patients with neuropsychiatric involvement have an increased rate of organ damage and a high degree of working incapacity, which illustrates the severity of disease in this subgroup.

Activities of Daily Living↗

PubMed2002

Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden.

OBJECTIVE: To explore the risk factors that have been suggested to be associated with the development of SLE. METHODS: A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events. RESULTS: Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; >150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=2.3, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE. CONCLUSIONS: Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.

Adolescent↗

PubMed2001

Increased level of soluble HLA class I antigens in systemic lupus erythematosus: correlation with anti-DNA antibodies and leukopenia.

The concentration of soluble HLA class I (sHLA-I) was measured by ELISA in serum samples from 30 well-characterised SLE patients at high and low disease activity states and from 100 healthy controls. HLA-A allotypes in the patients were analysed by a PCR-based typing technique. A higher level of sHLA-I was found in SLE patient sera both at high and low disease activity than in controls (P< 0.001). The sHLA-I level was further increased during active disease (P< 0.01). Concentrations of sHLA-I correlated with anti-dsDNA antibodies at high disease activity, but not with disease activity as analysed by a modified SLEDAI. Numbers of leukocytes and lymphocytes, as well as levels of C1q and C3 correlated inversely with sHLA-I concentration. In five serial samples from ten patients the sHLA-I level co-varied with disease activity. Presence of HLA allotype A9 was associated with higher sHLA-I levels in both patients (P< 0.001) and controls (P< 0.001). We conclude that the increased sHLA-I concentration in SLE patients was related to several laboratory parameters reflecting disease activity suggesting that sHLA-I molecules are connected with the disease process. Increased sHLA-I level due to HLA-A allotype was not a disease susceptibility factor for SLE.

Adult↗

PubMed2001

Increased endothelial expression of HLA-DQ and interleukin 1alpha in extra-articular rheumatoid arthritis. Results from immunohistochemical studies of skeletal muscle.

OBJECTIVE: To investigate markers of endothelial activation in muscle biopsies from rheumatoid arthritis (RA) patients with and without extra-articular manifestations (ExRA). PATIENTS AND METHODS: Nine consecutive ExRA patients were compared with nine RA controls without ExRA, matched for age, sex and duration of RA. Muscle biopsies were obtained from the lateral vastus or anterior tibial muscle. Macrophage and lymphocyte CD markers, HLA molecules, cytokines and adhesion molecules were investigated using immunohistochemistry, and stainings were evaluated using computer image analysis and conventional microscopy. Serum concentrations of soluble adhesion molecules, tumour necrosis factor alpha (TNF-alpha) and rheumatoid factor (RF) were determined using immunoassays. RESULTS: The number of HLA-DQ-positive capillaries (P=0.039) and the expression of interleukin 1alpha (IL-1alpha) in endothelial cells (mean pairwise difference 0.26%; 95% confidence interval 0-0.52) were increased in ExRA patients compared with non-ExRA controls. There were no signs of inflammatory cell infiltrates or fibre degeneration. Serum levels of TNF-alpha, the soluble form of intercellular adhesion molecule 1, the soluble form of vascular cell adhesion molecule 1 and IgM RF were increased in the ExRA group. CONCLUSION: The increased expression of HLA-DQ and IL-1alpha may indicate systemic endothelial activation in extra-articular RA, which could be of importance for cardiovascular comorbidity and mortality in such patients.

Aged↗

PubMed2001

Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden.

The objective of this study was to identify all malignancies in an inception cohort of SLE patients in southern Sweden and compare with the observed frequencies and spectrum of malignancies in the general population. All adult incidence cases of SLE in a defined population during the period 1981-1996 were retrieved from a prospective database and the cases were followed to endpoint or through 1998. The SLE cohort registry was aggregated with the National Cancer Registry to identify all malignancies by date, type and outcome. Standardized morbidity rates (SMR) were calculated based on the sex- and age-matched general population of the region. Sixteen malignancies occurred in 13 patients out of a total of 116 SLE patients observed for 1086 patient-years. The SMR for all cancers detected was 2.24 (confidence interval 0.6-5.7) for males and 1.02 (confidence interval 0.4-2.1) for females and thus indicative of no general increase in malignancies. However, the SMR for non-Hodgkin lymphoma was 11.63 (confidence interval 1.4-42.0), for pulmonary cancer 5.55 (confidence interval 0.7-20.1) and prostatic cancer 6.41 (confidence interval 1.3-18.7) all significantly increased. The increase in prostatic carcinoma disappeared when only cases occurring after a latency period of 3y after SLE diagnosis were included. In this comprehensive inception cohort of SLE no increase in relative risk of malignancy overall was found, but the frequencies of non-Hodgkin lymphoma and pulmonary cancer were increased, possibly also the frequency of prostatic carcinoma.

Aged↗

PubMed2000

Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus.

We have previously reported linkage of systemic lupus erythematosus to chromosome 2q37 in multicase families from Iceland and Sweden. This locus (SLEB2) was identified by linkage to the markers D2S125 and D2S140. In the present study we have analyzed additional microsatellite markers and SNPs covering a region of 30 cM around D2S125 in an extended set of Nordic families (Icelandic, Swedish, and Norwegian). Two-point linkage analysis in these families gave a maximum lod score at the position of markers D2S2585 and D2S2985 (Z = 4.51, PIC = 0.65), by applying a "model-free" pseudo-marker linkage analysis. Based on multipoint linkage analysis in the Nordic families, the most likely location of the SLEB2 locus is estimated to be in the interval between D2S125 and the position of markers D2S2585 and D2S2985, with a peak multipoint lod score of Z = 6.03, assuming a dominant pseudo-marker model. Linkage disequilibrium (LD) analysis was performed using the data from the multicase families and 89 single-case families of Swedish origin, using the same set of markers. The LD analysis showed evidence for association in the single-case and multicase families with locus GAAT3C11 (P < 0.0003), and weak evidence for association was obtained for several markers located telomeric to D2S125 in the multicase families. Thirteen Mexican families were analyzed separately and found not to have linkage to this region. Our results support the presence of the SLEB2 locus at 2q37.

Base Sequence↗

PubMed2000

A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q.

To identify chromosomal regions containing susceptibility loci for systemic lupus erythematosus (SLE), we performed genome scans in families with multiple SLE patients from Iceland, a geographical and genetic isolate, and from Sweden. A number of chromosomal regions showed maximum lod scores (Z) indicating possible linkage to SLE in both the Icelandic and Swedish families. In the Icelandic families, five regions showed lod scores greater than 2.0, three of which (4p15-13, Z=3.20; 9p22, Z=2.27; 19q13, Z=2.06) are homologous to the murine regions containing the lmb2, sle2 and sle3 loci, respectively. The fourth region is located on 19p13 (D19S247, Z=2.58) and the fifth on 2q37 (D2S125, Z=2.06). Only two regions showed lod scores above 2.0 in the Swedish families: on chromosome 2q11 (D2S436, Z=2. 13) and 2q37 (D2S125, Z=2.18). The combination of both family sets gave a highly significant lod score at D2S125 of Z=4.24 in favor of linkage for 2q37. This region represents a new locus for SLE. Our results underscore the importance of studying well-defined populations for genetic analysis of complex diseases such as SLE.

Animals↗

PubMed2000

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Alleles↗

PubMed2000

Binding of immune complexes to erythrocyte CR1 (CD35): difference in requirement of classical pathway components and indication of alternative pathway-mediated binding in C2-deficiency.

Deficiency of complement components within the classical pathway is associated with increased risk for immune complex disease. However, C2-deficient individuals often have a mild disease and about 50% are healthy. To study the importance of the different components for immune complex clearance, bovine serum albumin (BSA)/anti-BSA complexes were opsonized in human serum and the binding to erythrocyte complement receptor type 1 (CR1, CD35) was measured in vitro. In C2-depleted serum the complexes were opsonized and bound to CR1 but the reaction needed a longer opsonization time than in normal human serum (NHS). In contrast, serum reagent lacking C1q, C4 or C3 did not promote binding in this assay system. We also demonstrated that elevated levels of factor B could restore binding of complexes to erythrocytes in C2-depleted serum via alternative pathway activation. These results indicate that in spite of lack of a complete classical pathway, C2-deficient individuals could retain some immune complex opsonizing activity via the alternative pathway. This finding could contribute to the understanding of differences in association between complement deficiency and immune-complex disease.

Antigen-Antibody Complex↗

PubMed2000

Predictors of extra-articular manifestations in rheumatoid arthritis.

OBJECTIVE: To identify clinical and genetic risk factors for extra-articular manifestations of rheumatoid arthritis (ExRA). METHODS: ExRA patients were identified retrospectively using predefined criteria in two hospital-based cohorts of RA patients, and compared to non-extraarticular RA controls from one of the cohorts, matched for disease duration. RESULTS: Forty-nine living and thirteen deceased cases of ExRA were identified. Extra-articular disease was predicted by the demonstration of antinuclear antibodies (Odds ratio (OR) 3.6; 95% CI: 1.4-9.1) and the presence of rheumatoid nodules within two years from RA diagnosis (OR 3.4; 95%, CI: 1.1-10.9) or at any time before ExRA onset (OR 2.8; 95% CI: 1.1-7.2). Male sex and rheumatoid factor did not affect the risk of ExRA. Although present in the majority of cases as well as controls, the disease associated HLA-DRB1 subtypes were not significant predictors of ExRA. CONCLUSION: Extra-articular manifestations of rheumatoid arthritis in a hospital based population were predicted by antinuclear antibodies and rheumatoid nodules.

Adolescent↗

PubMed2000

No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19.

OBJECTIVES: Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual seroprevalence in epidemiologically defined SLE populations has previously been reported. METHODS: Sera from 99 SLE patients from a defined area in Southern Sweden, representing 88% of all new SLE cases 1981-1995 within the Lund-Orup Health Care district with 175 000 adult inhabitants (> 15 years of age), and sera from 99 age and sex matched healthy controls were investigated for the presence of IgG parvovirus antibodies. Two different commercially available EIA kits were used; one using E coli synthesised parvovirus VP1/VP2 antigen, and one using baculovirus derived parvovirus VP2 antigen. RESULTS: The EIA using baculovirus derived antigen was more sensitive and surprisingly the controls were more often positive than the SLE patients were (79% versus 65%, chi(2) p=0.027). No difference between the groups was seen with the EIA using E coli derived antigen (46% versus 49%). Titration experiments indicated that the discordance between the two tests was a matter of sensitivity rather than specificity. CONCLUSION: No evidence was found of human parvovirus B19 infection being more prevalent among SLE patients. On the contrary, in one of the parvovirus EIAs the controls were more often positive than the SLE patients were.

Adolescent↗