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Complete C4B deficiency in black Americans with systemic lupus erythematosus.
We report 3 black American patients with systemic lupus erythematosus (SLE) in whom C4B was completely deficient in plasma. They all exhibited antibody against the nucleoprotein antigen SSA (Ro), as well as cutaneous involvement, features that have been previously associated with complement deficiency states. IgG antibody against cardiolipin was also present in 2 patients, in association with a biologic false positive test for syphilis in one patient, and with thrombocytopenia in another. This is the first description of the clinical presentation of complete C4B deficiency in blacks with SLE.
Major histocompatibility complex extended haplotypes in systemic lupus erythematosus.
In a study of 32 white patients with systemic lupus erythematosus from 28 families, 60 unique chromosome 6 haplotypes were defined. The MHC extended haplotype HLA-B8, -DR3, SC01, GL02 was strongly disease-associated (0.09 patients, 0.02 controls, RR = 4.5, C.I. = 1.6-12.4, P less than 0.05), while the corresponding haplotype with the GL01 specificity was not increased in frequency (0.05 in both patients and controls). In the present data, the increase in the haplotype bearing GL02 accounted entirely for the association between HLA-DR3 and SLE. Furthermore, the phenotype of complete C4A deficiency was also strongly disease-associated (patients 0.14, controls 0.02, RR = 8.5, C.I. = 1.8-37.0, P less than 0.05). The only other MHC association in these patients was an increased occurrence of the HLA-B17, -DR7, SC61 haplotype (patients 0.07, controls 0.01, RR = 6.0, C.I. = 1.8-20.6, P corr. less than 0.05). The relationship between MHC markers and autoimmune disease appears to be a result of an association with MHC extended haplotypes and complete complement component deficiencies rather than with individual alleles. It is important that future studies include family members so that such haplotypes can be defined.
[Functions and structure of complement inactivators in membrane proteins. 3). Membrane cofactor protein].
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Structure and activation of the early components of complement.
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Phylogeny of C4b-C3b cleaving activity: similar fragmentation patterns of human C4b and C3b produced by lower animals.
Functional and structural studies of the activated proteins of the complement system C4b and C3b have led to the identification of cleavage products resulting from the effect of the regulatory proteins, factor I, H, and C4b binding protein (bp). In this paper we report the results of studies that investigated the capacity of plasma or serum from a wide range of phylogenetic species to yield similar cleavage products. Sera and plasma from mammals, reptiles, amphibia, and fishes are capable of cleaving fluid phase human C4b and C3b, generating apparently the same fragments as observed using normal human serum: alpha 2, alpha 3, alpha 4 from the alpha' chain of C4b: and alpha-68, alpha-46, alpha-43, and alpha-30 from the alpha' chain of C3b. When C3b bound to a cell membrane is used C3c and C3dg are generated. The generation of these fragments from C3bi is a dose-dependent reaction. There is no correlation between the evolution of the species and the quantitative capability to degrade the substrates. Birds possess only a limited capability to degrade the alpha' chain of C4b and have no cleaving activity for C3b, whereas sera from more primitive vertebrate species (chondrichthyes and agnatha) fail to participate in the reaction. Contrary to other species, the proteins in fish serum or plasma responsible for the degradation of C4b and C3b show a unique requirement for Ca2+ ions. Magnesium and barium are less effective, and in their presence a 65,000 dalton intermediate product is observed. These results demonstrate that protein(s) displaying proteolytic activity for products of complement activation, probably related to I, H, and C4bp, are present in plasma of species whose evolution have preceded humans by 300 million years. Moreover, the recognition of human substrates and the generation of fragments identical to those produced by human serum suggests that human C4b and C3b share structural characteristics with their evolutionary ancestors in the serum or plasma of the species studied.
[Detection of in vitro-bound complement components on vascular endothelial cells].
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The cytolytic attack mechanism of complement.
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Biological functions of the complement system.
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Activation of rat complement by soluble and insoluble immune complexes of rat IgA.
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Studies on the mechanism producing solubilization of immune precipitates in the serum of patients with primary IgA nephropathy.
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Anaphylatoxin levels in human aqueous humor.
Radioimmunoassay was used to measure levels of C3a, C4a, and C5a in aqueous humor from 13 normal eyes, 8 noninflamed eyes with a history of surgery or inflammation, and 14 eyes with anterior uveitis. The authors were unable to measure levels of C3a, C4a, or C5a in normal aqueous humor. In noninflamed aqueous humor from eyes with a history of surgery or inflammation, the authors were unable to measure levels of C4a or C5a, but were able to measure low levels of C3a in 3/8 patients. In aqueous humor from eyes with anterior uveitis, the authors were able to measure levels of C3a in all 14 patients, C4a in 9/14 patients, and C5a in 5/14 patients. Patients with severe anterior uveitis had higher levels of C3a than those with moderate anterior uveitis. The higher ratios of anaphylatoxin to protein levels in inflamed aqueous humor, when compared to normal plasma or noninflamed aqueous humor, suggested that complement was being activated by either the classical or alternative pathways in inflamed aqueous humor. Measurable levels of C3a without detectable C4a in five patients with anterior uveitis suggested alternative pathway activation of complement.
Complement activation produced by biomaterials.
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[Activation of complement during cardiopulmonary bypass--comparative study using 4 different oxygenators].
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Covalent binding properties of the C4A and C4B isotypes of the fourth component of human complement on several C1-bearing cell surfaces.
In a previous study we demonstrated that the thioester-mediated transacylation of the human C4B isotype onto sheep erythrocytes (ES) was approximately fourfold more efficient than that of C4A. Moreover, although C4B formed predominantly ester linkages, C4A displayed a preference for amide bond formation. We therefore suggested that the relative functional activity observed for the two isotypes would be a combined reflection of their nucleophilic preference and the surface composition of the C1-bearing target. The present study tests this hypothesis. Chemical modification of amino groups on Es with ethylacetimidate produced a twofold decrease in the C1-dependent binding of C4A isotype, while having a negligible effect on C4B binding. Furthermore, with human erythrocytes and two human leukocyte cell lines, K562 and U937, the C4B to C4A deposition ratio decreased from greater than 4 with ES to between 1.5 and 2. Irrespective of the target, C4A and C4B maintained their preference for forming amide and ester bonds, respectively. Interestingly, SDS-PAGE profiles of radiolabeled C4A and C4B, which had been covalently deposited on the various cells, suggested a further degree of transacylation specificity, as the two isotypic alpha-chains sometimes bound to different membrane components. These differences were not easily accounted for by simple differences in the abundance of the preferred nucleophile for each isotype on a given surface constituent, nor were they due to the preferential binding of one isotype to the sensitizing antibody. We speculate that nascent C4B may contain a substrate binding site that facilitates productive attack on the thioester carbonyl by molecules containing the class of nucleophile preferred by each isotype.
[Significance of the study of complement in glomerulonephritis. Research on some serum complement fractions and their detection in renal biopsies with the use of microscopy and immunofluorescence].
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Serum complement levels in cerebral malaria.
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[Research on correlations between immuno-nutritional parameters and oncologic stage in patients operated on for cancer of the stomach].
A correlation was sought, in 40 patients operated on for gastric cancer, between a number of immunological and nutritional variables and oncological stage. Prealbumin, transferrin, C3, C4, total complement (CH100), total serum lymphocytes, IgG, IgA and IgM were evaluated preoperatively prior to commencing any nutritional treatment. Statistical analysis was performed with a view to assessing whether the values of the above-mentioned parameters, taken singly or as a whole, differed in the 4 in the 4 oncological stages (UICC 1978). Analysis of individual parameter values showed a significant difference between stage I and stage IV with regard to prealbumin and between stages I and II with regard to C3 (p = 0.0165 and p = 0.0329, respectively). When evaluating the 9 parameters as a whole, no significant differences emerged, though such differences might be detected on increasing the study population and by adopting statistical procedures aimed at eliminating the least significant variables from the model.