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Biomedical subjects

G Sturfelt

Publications and source records attributed to G Sturfelt.

At least 55 records · Page 3Linked to original sources
PubMed2000

Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies.

The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.

Adult↗
PubMed2000

Toxic effects of SLE serum on normal monocytes in vitro: cell death induced by apoptosis related to complement dysfunction.

The aim of this study was to assess toxic effects of systemic lupus erythematosus (SLE) serum on blood peripheral mononuclear cells from healthy donors and to evaluate if complement activation was involved. Monocytes from a healthy donor were incubated with 20 sera from ten SLE patients in both high and low disease activity states. After incubation non-adherent cells were analysed by flow cytometry. Serum from six SLE patients induced an increased cell death, four in active disease only, one in the inactive state and one in the active and the inactive state. Five of these sera, three with high and two with low disease activity, induced an increased apoptosis in the monocytes. Proportion of apoptotic cells correlated inversely with C1q and C3 concentration in the active disease sera, but not with disease activity as evaluated by SLEDAI. Apoptosis could be induced by addition of active C1s or antigen/antibody complexes to normal serum before incubation. Serum with complexes added induced increased tumour necrosis factor-alpha secretion from mononuclear cells, but SLE patient sera did not. The results demonstrate that the toxic effect of serum from SLE patients on healthy monocytes is explained by induction of apoptosis. The induction process is suggested to be connected with complement activation in the serum.

Adolescent↗
PubMed2000

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison.

OBJECTIVE: To compare patients with systemic lupus erythematosus (SLE) from different centers with respect to demographics and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and to assess whether the SLICC/ACR DI changed over time, and whether initial DI scores were related to outcome. METHODS: Members of SLICC completed DI scores and patient demographics on patients followed in their centers. Information was provided at 2, 5-10, and > 10 years of followup. Data were entered on computer and analyzed on SPSS/PC+ and SAS using descriptive statistics and analysis of variance. RESULTS: Information for 1297 patients within 2 years of first clinic visit was submitted from 8 centers. There were 1187 women and 110 men with a mean age at diagnosis of SLE of 32 years. Seven hundred sixty-two were Caucasian, 423 were black, and the remainder were of other races. There were more blacks in the American centers than in Canadian or European centers. Five centers provided information for the 3 time periods. The DI increased over time. Ninety-nine patients had died. Higher SLICC/ACR DI scores were documented in patients who went on to die. CONCLUSION: The SLICC/ACR DI is a valid measure for damage in SLE.

American Medical Association↗
PubMed2000

Novel roles of complement in systemic lupus erythematosus--hypothesis for a pathogenetic vicious circle.

We propose that impaired complement function enhances a pathogenetic vicious circle in SLE. In this process, induction and clearance of apoptotic cells is central. Apoptosis could be triggered by various etiological factors, such as infection, UV light, and drug reactions. Clearance of apoptotic material is reduced when complement function is impaired. Apoptosis leads to increased exposure of nuclear antigens to the immune system, to which estrogenic hormones could contribute. This could in turn lead to activation of autoreactive B cells, autoantibody production, and immune complex formation, all of which is accelerated by hypocomplementemia. Immune complexes may, at least partly via complement dependent mechanisms, accelerate apoptosis.

Apoptosis↗
PubMed2000

Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis.

OBJECTIVE: To identify all new cases of systemic lupus erythematosus (SLE) within a defined area in Southern Sweden with validated methods of retrieval, and to compare 2 cohorts assembled during 1981-86 and 1987-91. METHODS: The catchment area, the health care district of Lund-Orup, had during 1981-91 a mean adult population (> 15 years of age) of 172,300 individuals. During 1987-91 we identified 379 individuals with potential SLE diagnosis from diagnosis registers and from central laboratory databases. Out of these, 121 had a previously known SLE diagnosis. All patient records were reviewed and patients with possible SLE not already known at the SLE unit were invited and examined. Organ damage was recorded as the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Forty-one new SLE cases were diagnosed during 1987-91, giving a median annual incidence of 4.8/100,000 inhabitants, with a median age at diagnosis of 47 years. The incidence is similar to that found 1981-86 (4.5/100,000/year) in the same population using the same methods for retrieval. Age and sex-specific incidence 1981-91 was notably highest at the age of 65-74 (14.1/100,000/year) in women and age 65-74 (3.2/100,000/year) in men. The point prevalence on December 31, 1986, was a 42/100,000 and on December 31, 1991, 68/100,000. The 5 year survival was 93% and 10 year survival 83%. While overall survival was not decreased, 10 year survival was slightly reduced compared with an age and sex matched healthy population (p = 0.03). In the 1987-91 cohort the sensitivity of the American Rheumatism Association criteria was 92.7% and the specificity was 94%. The frequency of renal manifestations was decreased in the latter cohort. The damage rate was highest during the first year and then constant during a 5 year followup, and was similar in the 2 cohorts. Damage that related to atherosclerosis was common and cardiovascular disease was the most common cause of death. CONCLUSION: The incidence of SLE in Sweden was notably constant during the 11 years 1981-91. Mortality was low and only late mortality (> 10 years disease duration) exceeded that in an age and sex matched control population. Atherosclerosis was the main cause of damage and mortality. Specificity and sensitivity of the ACR classification criteria are high in this epidemiologically recruited cohort.

Adolescent↗
PubMed1999

DNA levels in circulating immune complexes decrease at severe SLE flares-correlation with complement component C1q.

The objective of this study was to investigate the relationship of DNA content in circulating immune complexes with disease course and activity in SLE. The DNA content in circulating immune complexes containing anti-DNA antibodies of IgG class was determined in serial samples from 28 patients with SLE by a quantitative immunochemical assay. The patients presented various active disease manifestations over 5-55 months. Disease activity (SLEDAI-score), drug treatment and ACR-criteria were recorded. Levels of anti-dsDNA, CRP, leukocytes, complement components C3, C4 and C1q were measured. Patients with severe flares and high SLEDAI scores had low Clq levels at onset of active disease manifestations. The patients with low C1q serum levels during flare (n=13) had significantly lower amounts of DNA in immune complexes than patients with normal Clq (P=0.001). Levels of DNA in immune complexes correlated with Clq at flares (r=0.62, P<0.0001) and correlated inversely with SLEDAI scores (r=-0.47, P=0.012). In conclusion, the low levels of DNA in circulating immune complexes found in severely ill SLE patients with concomitantly low serum concentrations of Clq prior to flares might be related to tissue deposition of immune complexes.

Antibodies, Antinuclear↗
PubMed1999

A comparison of genome-scans performed in multicase families with systemic lupus erythematosus from different population groups.

Systemic lupus erythematosus is a disease of unknown etiology. Multiple genetic factors are believed to be involved in its pathogenesis. In addition, and due to genetic heterogeneity, these factors and/or their combinations may be different in different ethnic groups, while some might be shared between populations. We have performed genome scans in multicase families from three different population groups, two from Northern Europe, with a high degree of homogeneity, and the third from a recently admixed population of Mexican Mestizos. Although our family material is relatively small, the results presented here show that using family sets from well defined populations are sufficient to detect susceptibility loci for SLE. Our results also reveal the chromosomal regions most likely to contain susceptibility genes for SLE.

Ethnicity↗
PubMed1999

Low concentrations of immunoglobulin G antibodies to Salmonella serogroup C in C2 deficiency: suggestion of a mannan-binding lectin pathway-dependent mechanism.

The influence of complement on immune responses to polysaccharides is debatable. We examined the serum concentrations of IgM and IgG antibody against Salmonella O-antigen specific oligosaccharides representing the serogroups B, C and D, and against capsular polysaccharides of Streptococcus pneumoniae serotypes 6 and 23 in C2-deficient adults and in healthy controls. A sharp contrast of findings was found for antibodies against the CO antigen, an activator of the mannan-binding lectin (MBL) pathway of complement activation. The C2-deficient group showed normal IgM and markedly low IgG antibody levels. Similar findings were made in adults with low concentrations of MBL. This suggests that the recruitment of classical pathway C3 convertase through the MBL pathway is critically involved in isotype switching of antibodies against MBL pathway activating antigens during immune system maturation. The findings imply a new role of the MBL pathway, and an additional link between innate and acquired immunity. Specific IgM against BO was moderately low in C2 deficiency. Other differences for the Salmonella antigens were not found. Markedly raised IgM antibody levels against pneumococcal polysaccharides in C2 deficiency probably Salmonella reflected past infections. The absence of a concomitant increase of specific IgG might possibly be explained by impaired IgM to IgG switching.

Adult↗
PubMed1999

Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus.

We investigated whether IL1RN alleles separately or in combination with MHC class II variants, contribute to susceptibility to SLE and to analysed if IL1RN alleles are markers of disease severity. We investigated 81 patients from a defined area in southern Sweden diagnosed between 1981-1992 and 10 consecutive Caucasian families with multiple cases of SLE. As control group 189 healthy blood donors was used. PCR amplification of defined gene sequences was used in determining the IL1RN polymorphism as well as the MHC class II variants. The IL-1RA levels were measured by an immunoassay. We found an increased frequency of IL1RN*2 in both the epidemiological cohort and in the multicase families (P < 0.01). Alone IL1RN*2 and MHC class II (DR17,DQ2) separately increased the SLE risk moderately. The occurrence of IL1RN*2 and MHC class II variants DR17 and DQ2 together increased the risk to develop SLE by a sevenfold. The IL-1RA gene polymorphism did not correlate with disease severity or with renal involvement. We found an association between IL1RN*1 and arthritis (P < 0.001). Serum level of IL-1RA did not correspond to any specific IL1RN allele. An increased frequency of IL1RN*2 suggests the presence of a gene, implemented in SLE-susceptibility, in the IL1RN region of chromosome 2. IL1RN*2 and specific variants of MHC class II act in synergy to increase disease susceptibility. IL1RN*1 may be a marker of risk for development of arthritis.

Alleles↗
PubMed1999

Genetic analysis of the contribution of IL10 to systemic lupus erythematosus.

OBJECTIVE: To study the contribution of the IL10 gene to the susceptibility to systemic lupus erythematosus (SLE). METHODS: Analysis by fluorescent-semiautomated genotyping of a dinucleotide repeat located in the promoter region of the IL10 locus (microsatellite G). RESULTS: No significant difference was found in the frequencies of the microsatellite alleles of 330 Mexican patients with SLE compared to 368 controls from the same population. Two-point linkage analyses were carried out using 13 Mexican, 13 Swedish, and 8 Icelandic families with 2 or more cases with SLE. No linkage was revealed between IL10 and SLE, using a variety of parameter settings. CONCLUSION: Our results do not support that the IL10 gene contributes to the susceptibility to SLE in the populations we studied.

Dinucleotide Repeats↗
PubMed1998

Binding of properdin to solid-phase immune complexes: critical role of the classical activation pathway of complement.

The capacity of serum to support deposition of C3, properdin and factor B was studied by enzyme-linked immunosorbent assay using solid-phase immune complexes (IC) for activation of complement. Deposition of C3 and properdin occurred in fairly dilute normal human serum (NHS), but factor B uptake was hardly detectable. Alternative pathway-mediated deposition of C3 with slow kinetics was demonstrated in C2-deficient serum and in NHS depleted of C1q, factor D and properdin (C1qDP-depleted serum) after reconstitution with factor D and properdin. Efficient uptake of properdin required a functional classical pathway, in the presence of which C3 and properdin were rapidly deposited onto the IC. Judging from findings in C3-deficient serum, factor I-deficient serum, and C1qDPB-depleted serum, the uptake of properdin was strictly C3-dependent, and did not require the presence of factors B and D. Thus, C3b fixed to IC was the principal ligand for properdin in the assay. The findings could have biological implications relating to complement-mediated modification of immune complexes in disease.

Antigen-Antibody Complex↗
PubMed1997

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus.

OBJECTIVE: To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. METHODS: Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. RESULTS: The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. CONCLUSION: Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.

Adult↗
PubMed1997

Increased phosphate content in complement component C3, fibrinogen, vitronectin, and other plasma proteins in systemic lupus erythematosus: covariation with platelet activation and possible association with thrombosis.

OBJECTIVE: To investigate whether extracellular phosphorylation of plasma proteins takes place in vivo in patients with systemic lupus erythematosus (SLE), to determine possible correlations between phosphate levels and clinical and/or laboratory parameters, and to identify individual phosphorylated plasma proteins. METHODS: Sera from SLE patients were analyzed for total amounts of protein-bound phosphate by a colorimetric technique, and for levels of beta-thromboglobulin by radioimmunoassay. In addition, the ability of these sera to activate platelets, resulting in the release of protein kinase, was tested using an assay in which platelet-rich plasma from healthy blood donors was incubated with sera or immune complexes from SLE patients. In this assay, [gamma-32P]ATP was added, and 32P-labeled C3 was quantified. Phosphate in individual proteins was detected by Western blot analysis. RESULTS: 32P-labeled, activated platelets were able to phosphorylate exogenously added proteins, without the addition of ATP or cations. Platelet-rich plasma from healthy blood donors became activated by sera or by polyethylene glycol-precipitated immune complexes from patients with SLE, which led to the extracellular phosphorylation of plasma proteins, exemplified in the C3 assay. The phosphate content in plasma proteins was increased in SLE patients with previous thrombosis. The degree of phosphorylation increased up to 3-fold in serial samples obtained from 2 SLE patients during periods of disease exacerbation. Substantial phosphate increases were seen in C3 and fibrinogen. The changes were linked to platelet activation because of the observed covariation with the levels of beta-thromboglobulin. CONCLUSION: In SLE patients, the phosphate content in plasma proteins (including C3 and fibrinogen) increases due to platelet activation.

Adolescent↗
PubMed1997

Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus.

The objective was to study the relationship between the levels of interleukin-1 receptor antagonist (IL-1Ra) and disease activity and the acute-phase response in SLE patients with and without renal involvement. Twenty SLE patients who had distinct active clinical manifestations (eight glomerulonephritis, four systemic vasculitis without kidney involvement, nine skin rash, 12 arthritis, five serositis, four neuropsychiatric manifestations, three thrombocytopenia, one myositis and one haemolytic anaemia) were studied during a period of 8-12 months. Serum and plasma samples were taken at intervals of 6 weeks-4 months and tested for IL-1Ra, IL-1 beta, IL-6, IgG and anti-dsDNA, Clq, C3, C4 and C-reactive protein (CRP). IL-1Ra serum concentrations were increased in most SLE patients with active disease when compared to normal blood donors. However, at the time of flare, significantly higher levels of IL-1Ra were observed in patients with extra-renal disease as compared to other patients (median [range]: 363 [202-3041] and 4847 [268-27180] pg/ml for patients with and without renal involvement, respectively). This difference was not due to proteinuria. IL-1Ra levels did not correlate with SLEDAI score during flares, but they were elevated during flares in patients with extra-renal manifestations. When disease activity was at its highest, IL-1Ra concentrations correlated with IL-1 beta (r = 0.76; P < 0.001), IL-6 (r = 0.60; P < 0.01) and CRP (r = 0.61; P < 0.01), but not with C1q, C3, C4 and anti-dsDNA levels. The study showed that the pattern of inflammatory cytokines in active SLE varies in a manner that is dependent on which organs are involved. A relative absence of IL-1Ra response appears to be a feature characteristic of kidney involvement. IL-1Ra elevation clearly correlates with flares involving other organs.

Acute-Phase Reaction↗
PubMed1997

Serial analysis of autoantibody responses to the collagen-like region of Clq, collagen type II, and double stranded DNA in patients with systemic lupus erythematosus.

OBJECTIVE: To compare autoantibody responses to the collagen-like region of Clq (ClqCLR) with responses to double stranded DNA (dsDNA) and native rat collagen type II during changes of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: IgG antibodies to ClqCLR, dsDNA, and collagen type II were determined by ELISA in serial samples from 33 patients with SLE with different disease manifestations. Antibodies to dsDNA were also detected with the Crithidia luciliae test. RESULTS: Distinct antibody responses in conjunction with flare were observed, but the markers were more clearly related to clinical groups and to severity of disease than to changes of disease activity. Anti-ClqCLR antibodies were detected in 2/10 patients with mild flares, 7/12 patients with severe extrarenal flares, and in 10/11 of the patients with active lupus glomerulonephritis. Findings with regard to anti-dsDNA antibodies were similar. Antibody responses to collagen type II were detected in 7/12 of the patients with severe extrarenal disease, and were less frequently found in the other patients. ELISA absorption and elution experiments with anti-ClqCLR antibodies in the patient sera did not suggest cross reactivity with collagen type II and dsDNA. CONCLUSION: Serial investigation of 33 patients with SLE showed that antibodies to ClqCLR and dsDNA are markers of severe SLE, particularly SLE with kidney involvement. Antibodies to collagen type II are possible markers of severe extrarenal SLE with vasculitis and serositis. Analysis of anti-ClqCLR antibodies provided no evidence of cross reactivity with collagen type II and dsDNA.

Antibodies, Antinuclear↗
PubMed1996

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗
PubMed1996

Selective antibody reactivity with peptides from human endogenous retroviruses and nonviral poly(amino acids) in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate antibody responses to a broad panel of peptides derived from human endogenous retroviruses (HERVs) among unselected patients with systemic lupus erythematosus (SLE). METHODS: In sera obtained from 69 patients with SLE and healthy blood donors, immunoassay was used to measure levels of antibody against synthetic peptides derived from HERVs, exogenous retroviruses, and nonviral poly(amino acids). RESULTS: Measurement by immunoassay revealed increased frequencies of antiretroviral antibodies against 2 peptides derived from the env gene of the type C-like class, which includes ERV-9 and HERV-H, and against 2 peptides from the gag region of human T lymphotropic virus type I-related endogenous sequence 1, in patients with SLE. Antibodies to 2 nonviral peptides, polyhistidine and polyproline, were also overrepresented in patient sera. In 1 patient, longitudinal data obtained over a period of 12 years indicated that the concentrations of certain antiretroviral antibodies varied according to disease activity. CONCLUSION: Reactivity to certain type C HERV-derived antigens was found among patients with SLE. This reactivity could be explained by increased exposure to cross-reactive epitopes from essentially complete type C HERVs.

Amino Acid Sequence↗