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Biomedical subjects

L Truedsson

Publications and source records attributed to L Truedsson.

106 records · Page 6Linked to original sources
PubMed1985

Blocking of antibody complement-dependent effector functions by streptococcal IgG Fc-receptor and staphylococcal protein A.

Using haemolysis in gel, two bacterial IgG-binding substances, an Fc-receptor isolated from group A streptococci type M15, and protein A from Staphylococcus aureus, were shown to inhibit complement-mediated lysis of sheep erythrocytes sensitized with rabbit IgG. When the crude alkaline extracts of ten types of group A streptococci were tested to see whether streptococcal components other than Fc-binding material might affect lysis, the degree of inhibition was found to be correlated with Fc-binding activity. In no case was the lysis of IgM-coated cells inhibited. Opsonophagocytosis experiments showed that both purified streptococcal Fc-receptor and protein A impaired antibody complement-dependent killing by human polymorphonuclear leukocytes of each of two strains of group B streptococci (lacking IgG Fc-receptors). Furthermore, the impairment was ascribable to interference with the fixation of complement to the antibodies, as demonstrated in pre-opsonization experiments with one of the strains. Our results suggest that blocking of the binding of complement to IgG is an important virulence mechanism in Fc-receptor-bearing streptococci and staphylococci.

Animals↗
PubMed1984

Serum level of complement factor D in systemic lupus erythematosus--an indicator of glomerular filtration rate.

Serum levels of complement factor D, a low molecular weight (LMW) protein, were high and inversely correlated with glomerular filtration rate (GFR) determined in 19 patients with lupus glomerulonephritis (LGN). Factor D was significantly closer correlated with S-creatinine than were two other LMW proteins, beta 2-microglobulin and gamma-trace in 22 LGN patients. Close correlations between each of the LMW proteins and S-creatinine were found in patients with a non-inflammatory disorder, polycystic kidney disease. Slightly increased beta 2-microglobulin concentrations were found in 15 of 20 systemic lupus erythematosus (SLE) patients without renal involvement, while factor D and gamma-trace showed normal values in most of these patients. The findings imply that serum concentrations of complement factor D in SLE are mainly determined by the GFR.

Adolescent↗
PubMed1984

Inhibition of complement-mediated hemolysis in gel by rheumatoid factors.

When subjected to a hemolysis in gel (HIG) assay for the detection of complement deficiency, 9 of 37 sera from patients with classical rheumatoid arthritis produced impaired lysis of sensitized sheep erythrocytes. All sera were normal in a test for the alternative pathway and no major abnormalities were found within the complement system. Using a two-step HIG technique, with guinea-pig serum as the complement source, all sera were shown to inhibit lysis of sheep erythrocytes sensitized with rabbit IgG. Lysis of IgM-coated erythrocytes was not inhibited. The agglutination titers in a Waaler-Rose test, and the areas of inhibition in the two-step HIG assay with IgG-sensitized erythrocytes, were correlated (r = 0.80, p less than 0.001). Absorption of serum with rabbit IgG coupled to Sepharose 4B, reduced the capacity to inhibit immune hemolysis. The eluate from IgG-Sepharose contained rheumatoid factors and also inhibited immune hemolysis. The findings suggested that rheumatoid factors in serum were responsible for inhibition in the HIG assays used.

Animals↗
PubMed1983

Human factor D of the alternative pathway: purification and quantitation by enzyme amplified electroimmunoassay.

Purified factor D was prepared with a yield of about 30%. Monospecific antiserum was raised in rabbits. Immunochemical quantitation of factor D in serum and plasma was performed by electroimmunoassay and a sensitive staining technique based on enzyme amplification. Peroxidase-labeled swine antibodies to rabbit immunoglobulin were applied to the gel after electrophoresis. Immune precipitates were then visualized by staining for peroxidase activity. Factor D could be detected at 50 micrograms/l. The normal concentration of D in serum was 1.6 mg/l, as assessed by this assay.

Animals↗
PubMed1983

Complement components in 100 newborns and their mothers determined by electroimmunoassay.

Samples of blood were obtained from 100 healthy full-term women in labour and, after delivery, from the umbilical cord of their infants. By electroimmunoassay, complement components were quantitated in serum (C1q, C1r, C1s, C1 IA, C2, P, D. I, H, C6 and C7) or in EDTA-plasma (C4, C3, B, C5. and C). The concentrations of C7 in cord serum was twice that found by others using a functional assay. Concentrations of C1r, I and C6 in the cord sample were 50-60 per cent of those in healthy blood donors used as reference, and that of D was about 130 per cent. The cord serum and plasma concentrations of the remaining components agreed with previously reported values. The maternal levels of C2, C4, C3, B, H, C5 were 40-60 per cent higher than those of the reference.

Complement C4↗
PubMed1983

Complement factor D concentrations in normal sera: comparison of immunochemical and functional determinations.

The concentration of factor D (D) was determined in the sera of 144 healthy adults and 29 healthy children by enzyme amplified electroimmunoassay (EAE), and by a hemolysis in gel (HIG) assay for D. The 95% geometric confidence areas for D in adults were 75-143% as determined by EAE, and 65-171% by the functional assay. The concentrations were given in per cent of a reference serum pool containing 1.6 mg/l of D as measured by EAE. The correlation coefficient between D values obtained by the two methods was r = 0.52 (p less than 0.001). D levels were lower in children than in adults. In the EAE purified D, and pathological sera with very high D Concentrations, gave lower precipitation peaks with dilutions performed in buffer than with dilutions in D depleted serum or human serum albumin.

Adult↗
PubMed1982

Frequent occurrence of anti-rabbit IgM in IgA deficiency.

Analysis of IgA deficient sera revealed impaired hemolysis of sensitized sheep erythrocytes when tested by a hemolysis in gel (HIG) assay developed for detection of complement deficiencies. All sera were normal in a test for the alternative pathway. The impaired hemolysis was not related to complement aberrations but was caused by antibodies to rabbit IgM, demonstrated in 14 of 21 IgA deficient sera, by use of HIG technique and by agglutination. The presence of these antibodies was not related to age, sex or disease. One serum was further examined and the antibodies were shown to be of IgG class.

Adult↗
PubMed1981

Screening for deficiencies in the classical and alternative pathways of complement by hemolysis in gel.

Two assays based on hemolysis in gel were assessed for screening complement (C) component deficiencies. In one assay sensitized sheep erythrocyte (EA) were incorporated in agarose gel containing Ca2+ and Mg2+, in the other guinea pig erythrocytes (GpE) were used in the presence of Mg2+and EGTA. With few exceptions, fresh samples from healthy individuals produced homogeneous areas of complete hemolysis in both assays. Clearly aberrant patterns were observed in approximately 4% of healthy blood donors. Sera from patients having complete deficiencies of Clq, C2 or C4 produced clear lysis of GpE only, whereas in sera lacking C3 or C8 lysis was grossly impaired in both assays. Properdin deficient serum produced very slight lysis of GpE but normal lysis of EA. Reconstitution of these C-deficient sera gave normal lysis. Together, the two assays supplement immunochemical C3 and C4 determinations for screening out C disorders.

Animals↗
PubMedDate not supplied

Occurrence of autoantibodies against neutrophil granulocyte components in juvenile chronic arthritis.

This study included 96 patients with juvenile chronic arthritis of whom 47% had antinuclear antibodies (ANA). The highest frequency (58%) was seen in the oligoarticular subset, followed by the polyarticular and systemic subsets with ANA in 42% and 17% of the patients, respectively. Sixteen patients (17%) of whom 13 belonged to the polyarticular subset had granulocyte specific ANA (GS-ANA) with a titre greater than or equal to 1/50. Still another 22 patients (23%) had a borderline titre 1/25. GS-ANA were not found in any patient belonging to the systemic subset. Two of 16 patients with chronic iridocyclitis were GS-ANA positive while 9 were positive for ANA. None of the patients had circulating antibodies to neutrophil cytoplasmatic antigens (ANCA) detected by immunofluorescence or antibodies to elastase measured by ELISA. Antibodies to myeloperoxidase were found by ELISA in one patient, who showed no deviating clinical characteristics.

Antibodies, Antinuclear↗
PubMedDate not supplied

Complement activating rheumatoid factors in rheumatoid arthritis studied by haemolysis in gel: relation to antibody class and response to treatment with podophyllotoxin derivatives.

Complement (C) activating rheumatoid factors (RF) were measured in 16 patients with rheumatoid arthritis (RA) by a simple haemolysis in gel (HIG) assay. IgM-RF, but not IgG-RF or IgA-RF, measured by an enzyme linked immuno-sorbent assay, were closely correlated with C activating RF (r = 0.86). In neither assay did the concentrations of RF appear to be directly related to C1 activation as expressed by serum concentrations of C1r-C1s-C1 inactivator complexes or of C4. In the sera, C1q binding substances, measured by C1q binding assay, were markedly correlated with C activating RF (r = 0.88), whereas C1q binding substances detected by the C1q deviation test were not. Treatment with podophyllotoxin derivatives for 6 months clearly reduced patients' RF concentrations. The decrease of IgG-RF, IgA-RF and IgM-RF was significantly more pronounced than that of the IgG, IgA and IgM concentrations, respectively.

Adult↗
PubMedDate not supplied

False-positive Waaler-Rose test due to anti-rabbit IgM antibodies in IgA deficiency.

The presence of antibodies to rabbit IgM in an IgA deficient patient with degenerative arthropathy is described. The anti-IgM antibodies caused a false-positive Waaler-Rose test. Antibodies to rabbit IgM in titres greater than or equal to 1/8 were found in 20 of 35 IgA deficient individuals. No relationship between the patients' symptoms and the presence of these antibodies could be discerned and their biological significance is unknown. Two of 100 normal blood donors, none of 62 rheumatoid arthritis patients and 9 of 50 systemic lupus erythematosus patients showed anti-rabbit IgM antibodies in titres greater than or equal to 1/8. Unless an IgG fraction of antibodies is used for sensitization of erythrocytes in the Waaler-Rose test, the results may be misleading.

Agglutination Tests↗
PubMedDate not supplied

Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82).

A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects.

Cell Division↗
PubMedDate not supplied

Prospective analysis of C1 dissociation and complement activation in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the results of complement analysis for assessment of disease activity and severity, and prediction of flares in systemic lupus erythematosus (SLE). METHODS: Patients with mild extra-renal flares, severe extra-renal flares or flares of lupus glomerulonephritis were followed for eight months, with investigations being performed every second month. Findings in initial samples four months before the flares were compared with findings in a control group with stable disease. C-reactive protein, and circulating C1q, C4 and C3 were determined together with two types of complexes containing C1 inhibitor (C1 INH), C1 INH-C1r-C1s and C1 INH-C1r-C1s-C1 INH, and the C3 breakdown product C3d. RESULTS: Enhanced formation of C1 INH-C1r-C1s appeared to be a marker of low specificity and was mainly seen in patients with extra-renal disease. Concentrations of C1 INH-C1r-C1s-C1 INH, C3d, C1q and C3 clearly varied according to disease activity in patients with severe disease. Interestingly, high C1 INH-C1r-C1s-C1 INH values were found four months before the flares in all but one patient with lupus glomerulonephritis. Assessment of the relative predictivity for a subsequent flare indicated low C1q to be the most reliable marker, the predictivity of the complexes being: low C1q > high C1 INH-C1r-C1s-C1 INH > low C3 > high C3d > low C4. CONCLUSION: The importance of C1q and C1-related events in SLE may be underestimated. In addition, our results demonstrate the relevance of serial complement analysis for the assessment of disease activity and severity.

Adolescent↗