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Biomedical subjects

G Sturfelt

Publications and source records attributed to G Sturfelt.

At least 73 records · Page 4Linked to original sources
PubMed1996

Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): successful outcome in the recipient and induction of an SLE flare in the donor.

OBJECTIVE: To investigate the transfer of autoimmunity by allogenic bone marrow transplantation. METHODS: Bone marrow transplantation was performed in a 43 years old man with acute myeloid leukaemia (AML) in remission. The donor was his HLA identical brother who had a mild systemic lupus erythematosus (SLE). Autoantibodies, including antinuclear, anti-C1q, and anticardiolipin antibodies, were measured before and after transplantation. RESULTS: Transient mild graft versus host disease (GvHD) developed in the recipient in the weeks following transplantation. The donor had persistently high concentrations of anti-C1q antibodies to the collagenous region of the complement component C1q. Three months after transplantation the recipient developed antiC1q antibodies that persisted for two months. No other autoantibodies and no SLE-like manifestations appeared. Chronic GVHD started five months posttransplant and responded to intensified immunosuppressive treatment. Three years post-transplant the patient was in unmaintained remission. Within a few weeks after bone marrow donation the donor's disease was exacerbated with development of severe pulmonary alveolitis which required treatment with cyclophosphamide. CONCLUSIONS: When bone marrow transplantation was performed in a patient with AML with bone marrow from an HLA identical brother who had SLE, no evidence of transfer of disease was obtained. However, the recipient temporarily produced anti-C1q antibodies which was a characteristic feature of the donor's SLE and was probably produced by the transplant. The flare of the donor's SLE might be related to the bone marrow tap.

Adult↗
PubMed1996

Factor V:Q506 mutation and anticardiolipin antibodies in systemic lupus erythematosus.

Inherited resistance to activated protein C (APC resistance) is an important risk factor of venous thrombosis. It is caused by a point mutation in the gene coding for coagulation factor V, called FV:Q506. Arterio-venous thrombosis is a common and serious medical problem in patients with systemic lupus erythematosus (SLE). We studied the prevalence of the factor V mutation associated with APC resistance and IgG anticardiolipin antibodies (aCLs) in an epidemiological cohort of 78 Swedish SLE patients, to determine their roles as risk factors for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these patients was performed. Totally, 19 (24%) of the 78 SLE patients had thrombosis, 11 (14%) had venous thrombosis and 8 (10%) had a cerebral infarction caused by occlusion of cerebral vessels. Twenty-six (33%) SLE patients were aCL positive and 8 (10%) were heterozygous for the factor V mutation. Only one of the patients with venous thrombosis and one of the patients with cerebral thrombosis had the FV:Q506 mutation, whereas 3 patients with venous thrombosis and 5 patients with cerebral infarction were aCL positive. Eleven of 19 patients with heart valve disease were aCL positive, a statistically significant association (P = 0.01). In conclusion, we found no statistically significant association between venous thrombosis and FV:Q506 mutation or venous thrombosis and aCL positivity. There was, however, an association between heart valve disease and aCL positivity.

Adolescent↗
PubMed1996

TNF microsatellites in systemic lupus erythematosus-a high frequency of the TNFabc 2-3-1 haplotype in multicase SLE families.

TNFa, TNFb and TNFc microsatellites were analyzed in 102 SLE patients recruited from a defined area in Southern Sweden. Furthermore we studied 27 SLE patients belonging to 10 multiplex families in which a majority of the members were living within the same area in Southern Sweden. As a control population 98 healthy blood donors from the same region was used. The TNFa2 allele was found more often in the SLE patients (48%) than in the normal controls (33%) (P < 0.01). A low frequency of the TNFa4 allele (10%) vs 16% in controls was observed. The family study showed that the TNFabc haplotype 2-3-1 was more common in SLE associated haplotypes than in non-SLE haplotypes (P < 0.001). The 2-3-1 haplotype was associated with the extended haplotype MHC haplotype [HLA-B8,SC01,DR17]. The results suggest that TNF haplotypes do not constitute special markers of susceptibility to SLE but reflect the increased frequencies of specific intact haplotypes already known to be associated with the disease.

Adolescent↗
PubMed1996

C1 inhibitor deficiency in a patient with rheumatoid arthritis--increased risk of adverse effects of penicillamine?

We report the coincidence of hereditary angioedema and rheumatoid arthritis in a male patient and in his father. During treatment with D-penicillamine the patient developed a transient lupus-like disorder with glomerulonephritis that resolved when D-penicillamine was discontinued. He later was diagnosed with malignant lymphoma. Impaired classical complement pathway function could have contributed to development of the drug reaction.

Angioedema↗
PubMed1995

Binding to erythrocyte complement receptor type 1 of BSA/anti-BSA complexes opsonized by C4A3 or C4B1 in the presence of serum.

An in vitro model with human serum and human 0 Rh-negative erythrocytes was used for studies on preformed BSA/anti-BSA complex binding to complement receptor type 1 (CR1). The serum used was first depleted of Clq, factor D and properdin, then of C3, C4 or both and finally reconstituted with the desired proteins (serum reagent). With varying C4 concentrations and 100% C3 present, binding curves obtained for the two C4 isotypes were similar. When the serum reagent was not reconstituted with factor D and properdin there was no difference between the CR1 binding of normal serum and the partially reconstituted serum reagent, nor between the two C4 isotypes in this serum reagent. When C3 at 50% or 100% of normal concentrations was added to the serum reagent together with 100% C4A3 or C4B1, the C4B1-opsonized complexes showed more binding than the C4A3-opsonized complexes. At very low levels of C3 (< 25%) the binding could not be distinguished from the background. The results suggest that the binding of complement opsonized antigen/antibody complexes to erythrocyte CR1 is mediated mainly by C3, originating from activation of the classical pathway, and that the difference in properties between C4A and C4B does not have a major influence.

Animals↗
PubMed1995

Sharing of MHC haplotypes among patients with systemic lupus erythematosus from unrelated Caucasian multicase families: disease association with the extended haplotype [HLA-B8, SC01, DR17].

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease often clustered in families. We investigated the association between MHC haplotypes and SLE in multicase Caucasian families. METHODS: Ten consecutive families with 2 or more patients with SLE, in total 27 patients among 66 individuals, were studied. MHC haplotypes were determined by typing for HLA-A, B, C, DR, and DQ by serological and DNA methods. Complotypes were determined by protein typing and C4 gene polymorphism by DNA analysis. RESULTS: Fifty-four independent MHC haplotypes were found. Ten of the 31 haplotypes in the patients with SLE were examples of the extended haplotype [HLA-B8,SC01,DR17]. Six of these were found in 2 or more patients with SLE within the same family. All the 14 SLE sib-pairs in the families shared at least one haplotype and in 9 of the sib-pairs the shared haplotype was [HLA-B8,SCO1,DR17]. Three SLE associated haplotypes were [HLA-B7,SC31,DR15]. Four of the 27 patients with SLE were C4A deficient. Two C2 deficient siblings were homozygous for the haplotype [HLA-B18,S042,DR15]. CONCLUSION: We demonstrate that a very limited number of MHC haplotypes are associated with familial SLE. The haplotype [HLA-B8,SCO1,DR17] was closely related with the disease. There was no evidence suggesting familial SLE constitutes a disease subset. Determination of MHC haplotypes in multicase families is of value for assessment of disease susceptibility.

Adult↗
PubMed1994

Increased antiretroviral antibody reactivity in sera from a defined population of patients with systemic lupus erythematosus. Correlation with autoantibodies and clinical manifestations.

OBJECTIVE: The implied role of retroviruses in the pathogenesis of murine systemic lupus erythematosus (SLE) led us to study antiretroviral antibodies in a population-based SLE cohort. METHODS: Immunoassays using whole virus and synthetic peptides were performed on sera from 72 patients with SLE and 88 control subjects. RESULTS: Reactions with whole baboon endogenous virus occurred more frequently in patients with SLE, and correlated with the presence of anti-RNP and anti-Sm. Some retroviral env and gag peptides, several of which were similar to U1 small nuclear RNP, reacted more strongly in patients with SLE, and their presence was correlated with discoid rash, hematologic disorder, and other symptoms. CONCLUSION: These results provide circumstantial evidence for involvement of retroviruses in the pathogenesis of human SLE; further studies should be carried out using other techniques for measurement of retroviral expression.

Adult↗
PubMed1994

A simple enzyme immunoassay for measurement of immune complex solubilization utilizing preformed peroxidase-antiperoxidase complexes.

An enzyme immunoassay (EIA) was developed for measurement of complement-mediated solubilization of immune complexes. Preformed complexes consisting of horseradish peroxidase (Pe) and anti-Pe antibodies were incubated in diluted serum. After centrifugation the soluble complexes in the supernatant were quantitated by adding peroxidase substrate followed by measurement of absorbance. Kinetic analysis of revealed significant difference between normal and EDTA-treated serum similarly to a standard assay utilising immune complexes containing radiolabelled bovine serum albumin. The difference was most pronounced after incubation of immune complexes with serum for 40 minutes. Immune complex solubilization measured by EIA was reduced in sera from 10 patients with active systemic lupus erythematosus (SLE). In serially followed patients, flares of SLE were preceded by reduction of solubilization capacity. The EIA is a simple method for determining serum capacity to solubilize preformed immune complexes and might be considered as a routine test for assessment of complement function in diseases such as SLE.

Adult↗
PubMed1994

Significance of anti-entactin antibodies in patients with systemic lupus erythematosus and related disorders.

OBJECTIVES: To further evaluate the association of anti-entactin antibodies with clinical manifestations in patients with systemic lupus erythematosus (SLE) and related disorders. METHODS: Sera were analysed for anti-entactin antibodies from 79 patients with SLE, 38 patients with rheumatoid arthritis, 20 patients with progressive systemic sclerosis and five with Behçet's syndrome. Sera from 150 healthy blood donors and 20 patients with pneumonia were analysed as controls. To study the association of anti-entactin antibodies with severity and activity in SLE, 30 patients were assigned into three groups with 10 patients in each: (1) with mild manifestations; (2) severe disease without renal involvement and (3) frank lupus nephritis. Two blood samples from each patient were analysed, one from the active and the other from the inactive phase of the disease. Additionally, serial sera from 12 patients with SLE were also analysed. RESULTS: Thirty one patients with SLE (39%) had IgG, IgM or both anti-entactin antibodies. Twenty three of these patients (29%) had biopsy verified glomerulonephritis and 12 (50%) were positive for anti-entactin antibodies. Of the remaining 56 patients without apparent renal involvement, 18 (36%) were positive for anti-entactin antibodies. (chi squared = 2.77, p > 0.05). With the exception of rheumatoid arthritis where six patients (24%) had IgM anti-entactin antibodies, the antibodies were present much less frequently in other diseases (two patients with systemic vasculitis whilst none of the patients with PSS or Behçet's syndrome). Only one patient with pneumonia and none of the 150 sera from healthy blood donors had anti-entactin antibodies. Among Group 1, three (30%) were positive for IgG or IgM anti-entactin antibodies. Six (60%) patients in group 2, and five patients (50%) in group 3 were positive for anti-entactin antibodies. However, the difference between the presence of anti-entactin antibodies between group 1 and 2 or between group 1 and 3 was not significant (p = 0.15 and 0.19 respectively). There was no significant correlation between the titres of anti-entactin antibodies and total serum concentration of IgG (r = 0.141, p > 0.10) and IgM. (r = 0.130, p > 0.10). Furthermore, no significant correlation was observed between SLE disease activity index (SLEDAI) scores and the titres of IgG (r = 0.067, p > 0.10) or IgM (r = -0.033, p > 0.10) anti-entactin antibodies. CONCLUSION: The study demonstrates that anti-entactin antibodies are present in a significant number of patients with SLE and tend to be more common in those with severe disease, with or without nephritis, than in patients with mild disease manifestations. There is no correlation between the titre of anti-entactin antibodies and severity or activity of SLE.

Adult↗
PubMed1994

Cross-sectional analysis of the differences between patients with systemic lupus erythematosus in England, Brazil and Sweden.

This study is a cross-sectional analysis of the differences between SLE outpatients seen in Rheumatology departments at University centres in England, Brazil and Sweden, using a standard protocol. The demographic characteristics, extent and activity of disease of 209 patients with SLE were studied; 112 patients were seen in England, 33 in Brazil and 64 in Sweden. The median age of disease onset of Brazilian and English patients was 25 years and of Swedish patients 31.5 years. Disease activity was measured by the BILAG index. In most systems Brazilian patients experienced more activity than English patients and English patients more activity than Swedish patients. Non-Caucasians experienced more active disease than Caucasians. No sex or occupational differences were observed in disease activity. English patients were the most likely to have experienced photosensitivity, oral ulcers and haematological disorders, Brazilian patients renal disorders and Swedish patients discoid rashes. Brazilian patients were the most likely to be prescribed only one drug for treatment of SLE and to be taking steroids and the highest dose of steroids, in contrast to the European patients who were often prescribed steroids and an antimalarial agent or azathioprine. The results of this cross-sectional assessment of disease activity using a standardized instrument indicate that there are real differences in the extent and degree of activity of SLE in different national groups. This reflects a combination of genetic, environmental and social influences on disease expression and has implications for treatment and monitoring of SLE patients.

Adolescent↗
PubMed1994

Occurrence of anti-lactoferrin antibodies in patients with systemic lupus erythematosus, hydralazine-induced lupus, and rheumatoid arthritis.

Antibodies directed against neutrophil granulocyte components have gained an increasing importance in diagnosing systemic vasculitis diseases. The present study was aimed to investigate distribution of anti-lactoferrin antibodies in systemic lupus erythematosus, the hydralazine-induced SLE-like syndrome, and in rheumatoid arthritis compared to RA complicated with vasculitis. Antibodies were detected by ELISA and verified by Western blotting and inhibition assay. Sera positive for IgM were absorbed to remove the rheumatoid factor. IgG and IgM anti-lactoferrin antibodies were found in SLE in 5% and 10% respectively. All patients with hydralazine-induced SLE had antibodies of both isotypes and the antibody level declined rapidly after withdrawal of the drug. In rheumatoid arthritis no IgG anti-lactoferrin antibodies were found, but 20% of the patients with vasculitis had IgM antibodies. Anti-lactoferrin antibodies seem partly to discriminate between genuine and hydralazine-induced SLE, which might indicate a pathogenic relevance in drug-induced autoimmunity. In uncomplicated rheumatoid arthritis it can be concluded that anti-lactoferrin antibodies lack clinical, as well as pathogenic relevance.

Adult↗
PubMed1994

A comparison of 6 months' compliance of patients with rheumatoid arthritis treated with tenoxicam and naproxen. Use of patient computer data to assess response to treatment.

OBJECTIVE: To assess longterm compliance in patients with rheumatoid arthritis (RA) of 20 mg tenoxicam or 500-1000 mg naproxen taken daily and to evaluate patient computer data collection. METHODS: Three hundred and seven patients were treated in a double blind, randomized multicenter study for 6 months. The first 4 weeks of treatment data were collected daily via patient operated computers in parallel with standard assessment at weekly visits to the clinics. RESULTS: Daily patient data collection was more sensitive than weekly clinical assessments. Six months' compliance was 62% for tenoxicam and 67% for naproxen with comparable rates of withdrawal due to lack of efficacy or adverse drug experiences in both groups. The spectra of adverse drug events found were very similar for both drugs but the rates were higher than in short term studies. CONCLUSION: Daily computer data collection by patients is superior to classical clinical evaluation in drug studies. The longterm compliance of tenoxicam and naproxen are comparable when treating patients with RA.

Age Distribution↗
PubMed1993

Characterization of type I complement C2 deficiency MHC haplotypes. Strong conservation of the complotype/HLA-B-region and absence of disease association due to linked class II genes.

Fourteen individuals with complete C2 deficiency from 11 families and 3 heterozygous C2-deficient individuals from two families were investigated. In all the 24 independent C2-deficient haplotypes, the complotype S042 was present and the majority (21/24) was [HLA-B18,S042,DR2]. All carried the type I C2 deficiency C2 pseudogene with its characteristic 28 bp deletion. All but two haplotypes had 10 AC/GT repeats in the TNF alpha microsatellite polymorphism and all but one of the haplotypes were identical at or near HLA-B as assessed by RFLP using BstEII digestion and two genomic probes, R5A and M20A, located 100 and 38 kb centromeric to HLA-B, respectively. The exceptional haplotype was HLA-B40 with four AC/GT repeats at TNF-alpha. Three of the haplotypes were not DR2 based on generic and sequence-specific oligonucleotide typing. Another four haplotypes showed different DO-variants detected by RFLP analysis using BglIIand Mspl digestion. Thus, the [HLA-B18,S042,DR2] haplotype appears to be more fixed in the region between the complement genes and the HLA-B locus (96%) than in the region between the complement genes and DR (88%) and DO loci (71%). Of the 14 individuals studied, six had SLE or SLE-like syndromes and six had a history of severe infections although two were apparently healthy. Three of the six SLE patients and two individuals with repeated infections were homozygous for [HLA-B18,S042,DR2] and also homozygous for DQB1*0602 and the common DO variant. Thus, MHC class II genes linked to the C2 pseudogene do not appear to determine different clinical consequences of C2 deficiency.

Base Sequence↗
PubMed1993

Clustering of neutrophil leucocytes in serum: possible role of C1q-containing immune complexes.

Clustering activity for neutrophil granulocytes was generated in pooled normal human serum (NHS) by incubation of the serum with preformed IgG aggregates, but not in heat-treated NHS (56 degrees C, 30 min), indicating that the function was complement-dependent. Judging from results of experiments with complement-deficient sera, and serum depleted of C1q, factor D and properdin, recruitment of the complement system beyond C1 was not required for induction of the activity. Zymosan treatment of NHS resulted in some neutrophil clustering activity, but recombinant C5a had a limited effect. C1q added to heat-treated NHS in conjunction with performed IgG aggregates supported neutrophil clustering in a dose-dependent manner. The serum C1q inhibitor, a chondroitin 4-sulphate proteoglycan known to interact with the collagenous part of C1q, clearly reduced neutrophil clustering in heat-treated NHS supplemented with C1q and IgG aggregates. The C1q inhibitor also reduced the inherent neutrophil clustering activity of some sera from patients with systemic lupus erythematosus (SLE). Neutrophil clustering activity in SLE serum was earlier shown to be inversely related to the number of circulating neutrophils in vivo. Although the precise mechanisms remain unclear, we propose that C1q-containing immunoglobulin complexes mediate neutrophil clustering through C1q receptors, and that this might contribute to pathogenesis of immune complex diseases such as SLE.

Antigen-Antibody Complex↗
PubMed1993

Standardized ultraviolet-A exposure provokes skin reaction in systemic lupus erythematosus.

The immediate, 1 day and 14 days skin reaction was determined in 23 female SLE patients and 23 age-matched controls after standardized exposure to ultraviolet light of the UV-A wavelengths (320-440 nm). Eighteen of the patients and 12 of the controls were photosensitive by history. Eight separate sites on the buttocks were exposed to UV-A light, four sites at doses between 42 and 252 kJ/m2 and four sites with longpass filters (320, 345, 360 and 375 nm). The reactions on test sites were graded by two independent observers unaware of given doses of filter location. All patients and controls reacted with immediate erythema irrespectively of the presence or absence of photosensitivity. After 1 day, 39% of controls and 78% of patients had erythema and the reactions were more pronounced to longwave UV-A light (> 320 nm) in the patients (P < 0.001). After 14 days, six patients, but no control, had persistent erythema (P = 0.04). Interestingly, three of the four patients without anamnestic photosensitivity did not react on days 1 or 14, while the pattern seen in the controls on day 1 was totally unpredictable with regard to reported photosensitivity. These findings strongly suggest that a considerable proportion of SLE patients show pathological skin reactions to physiological doses of longwave UV-A and not only the far more studied shortwave UV-B (290-320 nm). The responsible chromatophore for the UV-A reaction is not known.

Adolescent↗
PubMed1993

Prevalence of the type I complement C2 deficiency gene in Swedish systemic lupus erythematosus patients.

The prevalence of type I complement C2 deficiency in Swedish systemic lupus erythematosus (SLE) patients was investigated by DNA analysis. The characteristic 28 base pair deletion was determined by polymerase chain reaction analysis followed by gel electrophoresis. Five of the 86 patients (5.8%) retrieved from a defined population of 160,000 individuals were heterozygous for the C2Q0 gene compared with one heterozygote of 100 local blood donors (1%), the difference in prevalence not being significant. Among 26 other SLE patients, two patients who are siblings were C2Q0 homozygous. No distinctive clinical features among the patients with C2Q0 genes were obvious, although none had renal involvement.

Autoantibodies↗
PubMed1992

Cardiovascular disease in systemic lupus erythematosus. A study of 75 patients form a defined population.

All patients with systemic lupus erythematosus in a prospective, epidemiologically based study within a defined area in southern Sweden were invited to participate in an investigation of cardiac function. From 1981 to 1988, 101 patients were included in the study, and 75 of them were investigated according to a fixed protocol by echocardiography, Doppler cardiography, electrocardiography (ECG) at rest and at exercise, and myocardial scintigraphy (in patients whose ECG became abnormal during exercise). IgG anticardiolipin antibodies (IgG aCL) were determined by ELISA. Twenty of the 75 patients (27%) had valvular disease and 12 of these (60%) had increased concentrations of IgG aCL, compared with 12 of 55 (22%) without valvular disease (p less than 0.01). Pericardial effusion was detected in 14 patients (19%) during the study period. Mild pulmonary hypertension was found in 11 patients (16%), who also had increased frequency of IgG aCL. Myocardial infarction had occurred in 7 patients, 3 of whom were women less than 40 years of age. Echocardiography revealed regional hypokinesis or akinesis in 5 of the patients with myocardial infarction. Exercise testing revealed low work capacity in 13 of 54 patients (24%), the limiting symptoms being mainly exhaustion or musculoskeletal pain. An abnormal resting ECG was found in 9 of the patients participating in the exercise test. During exercise, abnormal ST-depression was observed in 8 patients, 2 of whom developed angina. Myocardial scintigraphy was performed in 6 of these patients, revealing reversible uptake defects in all. Prolonged glucocorticoid treatment was associated with valvular abnormalities as well as myocardial infarction. Valvular abnormalities and IgG aCL appeared to be risk factors for cerebral infarction.

Adult↗