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Biomedical subjects

U Mårtensson

Publications and source records attributed to U Mårtensson.

At least 19 recordsLinked to original sources
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

Complement activation in patients with systemic lupus erythematosus without nephritis.

OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.

Adult↗
PubMed1997

Hypocomplementaemia caused by C3 nephritic factors (C3 NeF): clinical findings and the coincidence of C3 NeF type II with anti-C1q autoantibodies.

OBJECTIVES: The main purposes were to document manifestations associated with prolonged or clinically unexplained C3 deficiency and to approximate how often hypocomplementaemia of this kind is caused by C3 nephritic factors (C3 NeF), i.e. autoantibodies to alternative pathway C3 convertases. We also wished to distinguish between C3 NeF types I and II and to assess coincident autoantibody responses to the collagen-like region of C1q (C1qCLR). SETTING: The investigation was based on serum samples referred to a specialized laboratory for complement analysis in the course of several years. SUBJECTS: Twenty-five persons with C3 concentrations lower than 0.43 g L-1, a third of the normal, were included in the study. RESULTS: Analysis using three methods provided evidence of C3 NeF in 20 persons with equal frequencies of C3 NeF types I and II. We also gave evidence of antibody specificity differences for the two types of C3 NeF. Six patients with C3 NeF type II showed antibodies to C1qCLR. Membranoproliferative glomerulonephritis was the predominant diagnosis and two patients had partial lipodystrophy reflecting the well-known association between these diseases and C3 NeF. Anaphylactoid purpura, systemic lupus erythematosus, and severe infection, mainly meningococcal disease, were also observed. CONCLUSIONS: The study group was probably fairly representative of C3 deficiency syndromes as encountered in clinical practice. The findings emphasize the heterogeneity of C3 NeF, and that acquired C3 deficiency syndromes caused by C3 NeF should perhaps be considered more often in diagnostic work.

Adolescent↗
PubMed1996

Human autoantibodies against Clq: lack of cross reactivity with the collectins mannan-binding protein, lung surfactant protein A and bovine conglutinin.

The collectins, a group of humoral C-type lectins, have globular and collagen-like regions and share structural features with the complement protein C1q. The question was asked if autoantibodies to the collagen-like region of C1q (anti-C1qCLR) might cross-react with collectins, such as mannan-binding protein (MBP), lung surfactant protein A (SP-A) and bovine conglutinin (BK). Anti-C1qCLR antibodies of the systemic lupus erythematosus (SLE) type and anti-C1qCLR antibodies of the hypocomplementemic urticarial vasculitis syndrome (HUVS) type were investigated. Cross-absorption and elution experiments combined with antibody detection by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis gave no evidence of cross-reactive anti-C1qCLR antibodies. However, one serum with HUVS type anti-C1qCLR antibodies contained anti-MBP antibodies that were cross-reactive with SP-A. Judging from results of ELISA inhibition experiments and immunoblot analysis, four SLE sera contained antibodies to native BK, while two sera with HUVS type anti-C1qCLR antibodies contained antibodies to epitopes of denatured BK. This might imply that autoimmunity to collagen-like structures is not restricted to C1qCLR in HUVS and HUVS/SLE overlap syndromes.

Animals↗
PubMed1994

Acute respiratory disorder, rhinoconjunctivitis and fever associated with the pyrolysis of polyurethane derived from diphenylmethane diisocyanate.

OBJECTIVES: A case is described of complex reactions associated with exposure to diphenylmethane diisocyanate (MDI), with some immunologic observations. METHODS: Medical history, clinical examinations, and analyses of immunologic parameters and the 4,4'-MDI-related amine 4,4'-diaminodiphenylmethane (MDA) in hydrolyzed serum and urine were used. RESULTS: The patient, a mechanic whose medical history suggested repeated attacks of a work-related pulmonary or systemic disease, was examined because of acute respiratory disorder, rhinoconjunctivitis, and a late systemic reaction after exposure to polyurethane pyrolysis products, including 4,4'-MDI (air level 15 micrograms.m3). Spirometry showed a partly reversible obstructive dysfunction, and a skin-prick test was positive versus isocyanates conjugated with human serum albumin (HSA). MDA was detected in hydrolyzed serum (5.6 ng.ml) and urine (1.6 micrograms.g creatinine-1). In serum, there were specific immunoglobulin (Ig) G (IgG1 and IgG4) and IgE antibodies to 4,4'-MDI-HSA and other isocyanates (phenylisocyanate, toluene diisocyanate, p-toluene monoisocyanate, hexamethylene diisocyanate) conjugated with HSA, a very high total IgE, a raised total IgG, and moderate neutrophilia and eosinophilia. The specific antibodies declined, but were still increased five years later. Furthermore, the values of circulating immune complexes were high. In vitro, the circulating immune complexes in serum increased after the addition of 4,4'-MDI-HSA. The patient had anti-Clq antibodies, which probably accounted for part of the circulating immune complexes. CONCLUSIONS: The reactions associated with MDI exposure (in combination with exposure to pyrolysis products) had features compatible with immediate hypersensitivity and with a complement-mediated immune-complex reaction.

Allergens↗
PubMed1992

Western blot analysis of human IgG reactive with the collagenous portion of C1q: evidence of distinct binding specificities.

An enzyme-linked immunosorbent assay (ELISA) with purified collagenous C1q fragments in the solid phase was used for detection of C1q-specific immunoglobulins in the sera of twelve patients with systemic lupus erythematosus (SLE) or the SLE-like disease hypocomplementemic urticarial vasculitis syndrome (HUVS). By clinical criteria, four patients had SLE, and three HUVS. Five patients had overlap syndromes. All patients demonstrated high concentrations of C1q-specific IgG and markedly low concentrations of circulating C1q. Detection of C1q-specific IgG in SLE sera was facilitated by employment of saturating concentrations of collagenous C1q fragments in the solid-phase ELISA. When added to SLE serum, immune complex-fixed C1q inhibited binding of IgG to the C1q fragments, whereas addition of C1q alone had limited inhibitory effects. Under similar conditions, using approximately equimolar amounts of C1q relative to solid-phase C1q fragments, no ELISA inhibition was obtained after addition of C1q or immune complex-fixed C1q to a HUVS serum. Even in large excess, purified C1q did not inhibit binding of HUVS-IgG to solid-phase C1q fragments. Thus, possible interactions between HUVS-IgG and native Clq are probably of low affinity. By Western blot analysis, IgG reactive with the B and C chains of C1q was found in the eight patients with evidence of HUVS, five of whom also showed IgG binding to C'-C' and A'-B' dimers of collagenous C1q fragments. Sera from SLE patients were negative by Western blot analysis. It seems likely that C1q-specific IgG in SLE primarily recognizes assembled C1q molecules or collagenous C1q fragments expressing conformational epitopes of bound C1q. Interestingly, patients with evidence of HUVS fairly consistently had zymogen (C1r-C1s)2 complexes in their serum, while patients with SLE showed high concentrations of complexes containing Cl inhibitor, C1r and C1s. Different binding specificities of C1q-reactive IgG could be of importance with regard to pathogenetic mechanisms in SLE and HUVS. There was no correlation between findings of C1q-specific IgG and a variety of autoantibodies associated with SLE and SLE-like disease.

Adolescent↗
PubMed1991

C1 subcomponent complexes and C2 cleavage in active systemic lupus erythematosus.

We studied the activation and C1 inactivator-dependent dissociation of the first component of complement, the C1q(C1r-C1s)2 complex, in relation to recruitment of the classical activation pathway in the circulation of 24 patients with systemic lupus erythematosus (SLE). The patients were divided into three groups on a clinical basis, and were investigated during flares of disease activity. Group I had mild symptoms, group II major extrarenal manifestations, and group III manifest renal disease. High serum concentrations of trimer complexes containing C1 inactivator, activated C1r and zymogen C1s(C1 IA-C1r-C1s) were found in the majority of the patients. Some patients with high C1 IA-C1r-C1s concentrations showed no evidence of classical pathway activation, indicating that C1 activation was controlled by the action of C1 IA at the C1r level. By contrast, formation in serum of tetramer complexes in which C1 IA was firmly bound to both C1r and C1s (C1 IA-C1r-C1s-C1 IA) was associated with C2 and C3 cleavage in EDTA plasma, and with manifest hypocomplementemia. Low C1 IA-C1r-C1s-C1 IA values were observed in conjunction with substantial C2 cleavage in a few patients. Thus, C1 IA-C1r-C1s-C1 IA may not always be a sensitive indicator of classical pathway activation. Efficient recruitment of the classical pathway was related to disease severity, with some overlap between the clinical groups. In conclusion, C1 dissociation with formation of C1 IA-containing complexes was consistently found in patients with active SLE. The results suggested that C1 IA-dependent control of C1 activation was of biological significance in the disease.

Adolescent↗
PubMed1990

Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and synovial fluid of patients with rheumatic disease.

During activation, the first component of complement C1q (C1r-C1s)2 is dissociated in conjunction with the formation of complexes containing C1 esterase inhibitor (C1-INH). Trimer complexes, with zymogen C1s associated with a firm C1-INH-C1r complex (C1-INH-C1r-C1s) can be distinguished from tetramer complexes C1-INH-C1r-C1s-C1-INH) in which C1-INH is firmly bound to both proteases. In the present study a two-stage electroimmunoassay was developed for the specific measurement of C1-INH-C1r-C1s. In the first step, C1-INH and its complexes were immunoprecipitated with anti-C1-INH during electrophoresis in the presence of Ca2+. In the second step, C1s contained in C1-INH-C1r-C1s was dissociated in the presence of EDTA and was measured by immunoprecipitation with anti-C1s. C1-INH-C1r-C1s were consistently found in normal sera. Normal sera did not contain C1-INH-C1r-C1s-C1-INH as assessed with a previously described ELISA procedure. Sera and synovial fluids from two groups of patients with inflammatory arthritis were investigated. In rheumatoid arthritis patients (n = 15) C1-INH-C1r-C1s complexes were usually found at high concentration both in serum and synovial fluid. C1-INH-C1r-C1s-C1-INH complexes were also present with values that were higher in synovial fluid than in serum, in accord with previous findings of classical pathway activation in the inflamed joints of the patients. Patients with spondylarthritic syndromes (n = 7) had serum and synovial fluid C1-INH-C1r-C1s concentrations that were comparable to those of the rheumatoid arthritis patients. If at all present, C1-INH-C1r-C1s-C1-INH were detected in trace amounts. Thus, C1 activation in patients with spondylarthritic syndromes appeared to be efficiently controlled at the C1r level. Distinguishing between C1-INH-C1r-C1s and C1-INH-C1r-C1s-C1-INH may prove of value in further studies of the activation and control of C1 in disease.

Animals↗
PubMed1987

C1 dissociation. Spontaneous generation in human serum of a trimer complex containing C1 inactivator, activated C1r, and zymogen C1s.

Activation of the C1 complex in the presence of C1 inactivator (C1 IA) is known to result in the formation of tetramer C1 IA-C1r-C1s-C1 IA complexes that are dissociated from C1q. Both C1r and C1s of the tetramers are present in their activated forms. The present investigation concerned the generation of trimer complexes containing C1 IA, activated C1r, and zymogen C1s (C1 IA-C1r-C1s). C1 IA-C1r-C1s were released from C1q and were formed in high concentration during prolonged incubation (1 to 3 days) of normal serum at 37 degrees C without addition of activators. By contrast, dissociation of C1 with formation of C1 IA-C1r-C1s-C1 IA was complete within 30 min at 37 degrees C, when the serum was treated with heat-aggregated IgG (1 g/liter). On size exclusion chromatography (TSK-4000), C1 IA-C1r-C1s and C1 IA-C1r-C1s-C1 IA emerged with apparent m.w. of 320,000 and 460,000, respectively. The composition of the complexes was examined by absorption of serum with F(ab')2 anti-C1s- or anti-C1r-coated Sepharose beads. Eluates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunoblotting. Under nonreducing conditions, heat-aggregated IgG-treated serum showed high concentrations of C1 IA-C1r (m.w. 202,000) and C1 IA-C1s (m.w. 194,000), while serum incubated at 37 degrees C without activators showed high concentrations of C1 IA-C1r but no C1 IA-C1s. Under reducing conditions, heat-aggregated IgG-treated serum showed m.w. 120,000 and 110,000 complexes of C1 IA and the C1r and C1s light chains, respectively. Uncleaved C1s and the m.w. 120,000 complex was found in serum that was incubated at 37 degrees C without activators. Consistent with results obtained by size exclusion chromatography, analysis by crossed immunoelectrophoresis and by electroimmunoassay showed that C1s could be released from C1 IA-C1r-C1s in the presence of EDTA.

Blood Protein Electrophoresis↗
PubMed1987

C1 activation and dissociation in disease.

The composition of complexes containing C1 inactivator (C1 IA), C1r and C1s was investigated in normal serum after activation of C1 under various conditions. Analyses were performed with PAGE of eluates from Sepharose beads coated with F(ab')2 fragments of anti C1s followed by immunoblotting with anti C1 IA, anti C1s or anti C1r. Eluates obtained from serum treated with aggregated IgG (AGG) contained C1 IA in complex with C1r and C1s with both subcomponents in activated form. Eluates from serum incubated at 37 degrees C for 1, 2 or 3 days without activators showed C1 IA complexed with activated C1r and with C1s in proenzyme state associated to the complex. On analysis of serum, treated as mentioned above, by a variant of the electroimmunoassay using an intermediate gel containing anti-C1 IA and with anti-C1s in the anodal gel the two types of C1r--C1s--C1 IA complexes could be distinguished. Investigation of fresh sera and synovial fluids from patients with rheumatoid arthritis in this assay showed complexes containing C1 IA and C1r-C1s in activated form in the synovial fluids, while C1 IA-activated C1r-proenzyme C1s complexes were found in the corresponding sera.

Arthritis, Rheumatoid↗
PubMed1985

C1 dissociation in serum: estimation of free C1q by electroimmunoassay.

A two-stage electroimmunoassay was developed for measuring macromolecular C1 (C1qrs) and free C1q. The method was based on Ca2+ dependent fixation of C1qrs to agarose, followed by immune precipitation of dissociated C1s in the presence of EDTA. Free C1q was estimated from the increase in C1qrs resulting from saturation of C1q in the samples with purified C1r-C1s. The assay system was studied under various experimental conditions. Combined analysis by electroimmunoassay and crossed immunoelectrophoresis indicated that part of the free C1q in undiluted normal serum could be attributed to physiological C1 activation. Owing to concentration dependent C1qrs dissociation the proportion of free C1q increased with the dilution of serum. Results obtained with serum and with purified C1qrs were consistent with the formation of an equimolar C1q:C1r-C1s complex. However, the capacity for C1r-C1s binding appeared to be higher in the purified system than in serum. Serum concentrations of free C1q were high in some of the patients with disease conditions characterized by increased C1 activation, such as systemic lupus erythematosus or primary biliary cirrhosis.

Complement Activating Enzymes↗
PubMed1981

Binding of purified C1 subcomponents, C1 inactivator and their complexes to immobilized heparin.

Under specified conditions purified C1q, activated C1r and C1s and C1r-C1s complexes were bound independently of Ca2+, to heparin-Sepharose, and could be eluted by an increasing salt gradient. Zymogen C1r and C1s, C1r-C1s complexes, C1 inactivator, and C1r-C1s-C1 activator complexes were not bound. However, at lower conductance Ca2+ independent binding of C14 occurred, which was utilized in the purification of C14 and C1s. In the presence of C1t (serum amyloid P component), C1s was firmly retained on heparin-Sepharose, which was probably due to formation of a C1s-C1t complex.

Amyloid↗