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Biomedical subjects

A B Laurell

Publications and source records attributed to A B Laurell.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Common epitopes in Clq and collagen type II.

An epitope common for collagen type II and Clq was demonstrated by specific binding of a monoclonal anti-collagen type II antibody, MAb B1, to purified Clq. This was further substantiated by the affinity shown between F(ab')2 fragments of anti-Clq antibodies and rat chondrosarcoma collagen type II. The interaction between MAb B1 and Clq was demonstrated in hemolytic assays, in an enzyme-linked biotin-avidin assay and by the binding of Clq to MAb B1 immobilized on Sepharose 4B beads. MAb B1 recognized only purified Clq and not the macromolecular Cl complex, indicating that the epitope for MAb B1 was situated in the collagen-like region in Clq, where Clq and Cls are anchored. The binding of the purified collagen-like fragment of Clq to radiolabelled MAb B1 confirmed these findings. The affinity between MAb B1 and Clq was significantly increased if Clq was first reacted with heat aggregated IgG, indicating a demasking of the reactive epitope on binding to the aggregated IgG. The present findings raise the question of the pathogenetic significance of the presence of anti-collagen type II antibodies and free Clq, both of which are frequently seen in high amounts in rheumatoid arthritis.

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↗
PubMed1986

C1 activation, with C1q in excess of functional C1 in synovial fluid from patients with rheumatoid arthritis.

Free Clq, in functionally active form was present in increased amounts in the synovial fluid of patients with rheumatoid arthritis. The presence of free Clq was associated with low concentrations of hemolytic C1, low C4 and raised amounts of C3dg/d fragments in the synovial fluid. The findings suggested intra-articular C1 activation with dissociation of C1 into free C1q and complexes containing C1r, C1s, and C1 inactivator. However, the immunochemical properties of synovial fluid C1r-C1s-C1 inactivator complexes appeared to differ from those of the complexes formed in serum, which hampered quantification with the assay used. Control patients with osteoarthritis or spondylarthritic syndromes did not show evidence of intra-articular complement activation, even though 1 patient with Reiter's disease had unexplained low concentrations of synovial fluid C4 and C3. The concentrations of circulating complement components were largely normal in the patients. Slightly increased concentrations of free C1q and C1r-C1s-C1 inactivator complexes in serum and C3dg/d fragments in EDTA plasma were observed, particularly in the patients with rheumatoid arthritis.

Adult↗
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↗
PubMed1985

Correlation among complement activation, protease inhibitors, and clinical course in acute pancreatitis in man.

Changes in complement levels and protease inhibitors were measured in plasma/serum and peritoneal fluid during 15 attacks of acute pancreatitis. The abnormalities found in the complement system and the protease inhibitors were most pronounced in severe attacks, especially in the peritoneal fluid. Depressed levels of C1q, C3, properdin, and factor I were found in blood on admission in severe attacks. A decrease during the first days of illness was found for C1q, C3, C4, properdin, factor I, and factor H levels in blood. There was a discrepancy between the low C1q and the high C1r and C1s levels in blood. Complexes of C1r-C1s-C1 inactivator and factor B conversion products were found, especially in the peritoneal fluid, denoting an activation of the complement system. High levels of trypsin in complex with alpha 1-protease inhibitor were found, both in blood and in peritoneal fluid, denoting the liberation of active trypsin in acute pancreatitis. The levels of the functional alpha 2-macroglobulin were low, especially in the peritoneal fluid. It is concluded that both classical and alternative complement activation take place in acute pancreatitis, starting in the peritoneal cavity. The magnitude of activation depends on the severity of the disease. Trypsin-induced activation of complement components may explain some of these changes.

Acute Disease↗
PubMed1979

Systemic capillary leak syndrome with monoclonal IgG and complement alterations. A case report on an episodic syndrome.

A case of the rare systemic capillary leak syndrome (SCLS) is described. The patient suffered 9 attacks with muscle pain, weakness and profuse sweating. He showed increased Hct values up to 79 percent and a decreasing plasma volume to about 50 percent of normal. During the attacks the patient was in a state of shock and BP was unmeasurable. Studies with 131I-labelled albumin during attack showed an increased transcapillary escape rate to about 20 percent/hour, compared to 6 percent when he was without symptoms. A monoclonal IgG with a constant concentration of about 5g/l was found. Studies of the complement system during attack showed low C4 values, disproportions among the C1 subcomponents and C1r-C1s-C1IA complexes, suggesting a complement activation via the classic pathway. Hereditary angio-edema was excluded by normal C1IA values. The complement activation might be part of the pathogenesis of the increased macromolecular permeability in this syndrome. A short review of cases described earlier is given.

Adult↗
PubMed1977

C1 subcomponents in acute pneumococcal otitis media in children.

Twenty children with acute pneumococcal otitis media were studied. In 6 children the infection ran a normal course and healed after the first episode and in 14 it relapsed. The serum levels of the immunoglobulins IgG, IgA and IgM were normal in all 20 children. Specific antibodies to pneumococcal polysaccharide were found in all cases, with no differences in the titers between the relapsed cases and those that healed. The complement components were quantitated with electroimmuno assay. G1q proved depressed in 60 per cent of the relapsed cases and in 16 per cent of the healed cases. C1r and C1s were disproportionally high compared with the C1q levels. Furthermore, crossed immunoelectrophoresis revealed abnormal complexes composed of C1r and C1s, and complexes composed of C1r, C1s and C1 IA. These complexes were more pronounced in sera from the children with relapsing otitis media.

Acute Disease↗
PubMed1977

Studies of C1 subcomponents in chronic urticaria and angioedema.

C1q, C1r, C1s, C3, C4 and C-1 IA were determined by electroimmunoassay in sera from 150 patients with chronic urticaria or angioedema. Abnormal C1q and C1s levels were found in about 30% of the patients. In seven sera C1r was not measurable due to the appearance of diffuse precipitates. The levels of C3 and/or C4 were decreased in five sera with aberrations of C1 subcomponents in the electroimmunoassay. None of the patients showed reduced C-1 IA levels in the electroimmunoassay. The presence in sera of abnormal C1 subcomponent complexes was studied by crossed immunoelectrophoresis. Sera from 11% of the patients contained C1r-C1s complexes. Increased amounts of alpha2 complexes (C-1r-C-1-S-C-1 IA) were found in 33% of the patients. A major part of the C1q in sera yielding abnormal C1r precipitates had the same electrophoretic mobility as isolated C1q and was not associated with the C1qrs complex. C1 activity in hemolytic tests was low in these sera as well as in sera with decreased C1q levels. In the esterolytic assay for C-1 IA low values were found in 14 patients. Repeated sampling and family studies in appropriate cases gave no evidence for genetically determined deficiencies of C1q, C1r or C-1 IA.

Angioedema↗