[Immunochemical determination of some complement components in sera studied at various temperatures].
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Genes, which are responsible for the effectivity of immune response are located on the chromosome 6 similarly as the genes of the class I and II of the major histocompatibility complex (MHC) together with the genes of some complement proteins (C4A, C4B, B factor/Bf/). The study investigates the interdependence between HLA configuration as well as complement protein allotypes (C4A, C4B, Bf) with the reactivity to HBV vaccination of ESRD [end stage renal disease]-patients. 153 ESRD-patients (68 females, 85 males; mean duration of hemodialysis therapy 8.2 +/- 5.1 years) were studied. Subjects were vaccinated (Gen-H-B-Vax-D; Merck, Sharp and Dohme, 40 micrograms/dosis i.m.) in the schedule at 0, 1, 2, and 6 month. Non-responders (NR) were defined when the anti-HBs antibody titer was below 10 U/liter. HLA typing was performed by means of microlymphocytotoxicity assay, whereas complement allotypes were estimated by using high voltage gel electrophoresis with subsequent specific immunofixation with antibodies against C4A, C4B and Bf. In the non-responders group [NR = 34] a) the significantly higher occurrence of single HLA-A1 and/or HLA-B8 and/or Cw4 or DR3 or DR7 or DQ2 have been found. In about 40% of NR HLA-A1, -B8, -DR3, or -DQ2 antigens occurred as homozygotes.
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To find protein-protein interactive sites in complement component C3, we examined regions of C3 that are proximal to sites of length polymorphism or indels in the C345 protein family. We reasoned that indels probably mark protein interactive sites because they usually involve residues at protein surfaces. To test for the involvement of individual indels, we examined the effects on complement function of synthetic peptides corresponding to indel-proximal segments of C3. We inferred that if such a segment made direct contact with a C3 binding protein, then the corresponding peptide might also bind to that protein and inhibit binding to C3. Twenty-one peptides were tested; four of these inhibited complement-mediated erythrocyte lysis at < or =100 microM and complement-mediated killing of Escherichia coli at about threefold higher levels. These results indicate that the four peptides act as specific inhibitors of complement. They also suggest that indels can be effective guides for locating interactive sites in C3 and in any protein that is a member of a protein family. Because only a linear sequence is required, a focus on indels may be particularly useful for identifying interactive sites in proteins for which a three-dimensional structure is unavailable.
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Five of twenty-three patients with paraproteinaemia (two IgM, three IgG) have been shown to exhibit marked classical pathway complement activation. The mechanisms of hypocomplementaemia proposed for the five patients are cryoglobulinaemia in one and in vivo immunoglobulin aggregation in the other four. Three further patients had a low C1q and three a low C3 unassociated with any other complement abnormality. No association with any particular IgG subclass or obvious clinical abnormality existed in association with hypocomplementaemia.
We examined the association of complement activation at a low temperature in vitro with hepatitis C virus infection in alcoholic patients. The incidence of cold activation among these patients was 4.1%, which was higher than the reported incidence of 1.7% among general patients consulting a hospital, and that of 0.5% among donors for blood transfusion. In any population, most cases that showed cold activation were HCV antibody positive. The difference between the incidence of cold activation among HCV antibody positive cases in alcohol high consumers (6/21) and that in control patients (42/103) was regarded as nonsignificant. The higher incidence of cold activation among alcoholic patients may not directly associate with high alcohol consumption and may associate with higher incidence of HCV infection among the group.
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Renal involvement is found in 20 to 50% of cases of Partial lipodystrophy (PLD). We report 8 cases of PLD of which 6 had a glomerular nephropathy and 2 had no renal disease but all had persistent hypocomplementemia and 5 had circulating nephritic factor (C3NeF). The analysis of these cases and of all the cases reported in the literature shows the specificity of the glomerular involvement. Membranoproliferative glomerulonephritis (MPGN) with dense intramembranous deposits is a constant finding in PLD with renal involvement. This variety of MPGN is well known for being associated with persistent hypocomplementemia. However, the presence of hypocomplementemia and C3NeF in patients with PLD but without nephritis raises the question of the interrelationship between alternative pathway complement activation and the development of MPGN with or without lipodystrophy. There is no valid explanation in the present state of knowledge for the association of partial lipodystrophy hypocomplementemia, and MPGN. From the answer to this problem should emerge a better understanding of the role of complement in renal disease and in particular in the unusual form of glomerular injury seen in MPGN.
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The complement system was examined in fifty patients with acute, apparently uncomplicated measles; forty-six were children less than 10 years old. Twenty showed evidence of pathological complement activation. In thirteen of these the pattern was consistent with activation of the classical pathway while in the other seven data suggested utilization of an alternative pathway. An additional eleven patients had isolated reduction in Clq without alteration in concentration of other components; these were excluded from the classical pathway group. No patient had detectable immune complexes or C3 splitting activity in serum; however, it is suggested that the abnormal complement patterns observed are likely to indicate the presence of circulating immune complexes in a high percentage of patients with this infection.
The Spitting Cobra, Naja nigricollis, is widely and densely distributed in Africa. Fourteen patients with proven N. nigricollis bites, who were seen in the savanna region of Nigeria, did not exhibit the neurological signs, such as cranial nerve lesions and respiratory paralysis, expected following Elapid poisoning. All had local swelling, in eight cases involving the entire limb, and ten developed local tissue necrosis. Spontaneous haemorrhage was detected in three cases and was the probable cause of death in one of them; the other death in this series was unexplained. Haematological abnormalities included prolonged clot lysis anf failure of clot retraction due to a platelet defect. There was no specific deficit in clotting factors and a delayed rise in fibrin degradation products was attributed to extensive tissue damage at the site of the bit. Most patients showed depletion of complement component C3 and glycine-rich beta-glycoprotein (GBG), suggesting activation of the alternative pathway of complement fixation. There was evidence of hepatocellular damage in two out of six patients investigated. There was no evidence that specific polyvalent antivenoms, used in doses of up to 80 ml, prevented any of the effects of N. nigricollis venom. Clinical laboratory diagnosis is discussed. In the past many bites were wrongly classified as viper bites on the basis of clinical findings. Immunodiagnosis is a promising method for assessing the true importance of N. nigricollis bite in West Africa.
By way of example of a patient and his family and by means of the literature, the present knowledge of pathogenesis and therapy of hereditary non-allergic angioneurotic edema has been reviewed.
BACKGROUND: Hitherto, not very numerous investigations provided so far only few often controversial findings on the importance of interleukin-10 (IL-10) in systemic lupus erythematosus (SLE). The objective of the present investigation was to assess whether there exist practically applicable relations between the serum level of IL-10, clinical and laboratory indicators of activity of the disease and serum levels of selected cytokines or their soluble receptors. METHODS AND RESULTS: The authors analyzed a group of 23 patients with SLE (23 women and 1 man, median age 37 years). Interleukin-10 and other cytokines were examined by the ELISA method, the clinical activity of the disease was evaluated by the ECLAM system (European Consensus Lupus Activity Measurement). Elevated IL-10 values (> 5 pg/ml) were assessed in 10 (43%) patients. Correlation analysis (Pearson's test, p < 0.05) revealed statistically significant relations between IL-10 levels and the activity of the disease, values of antibody levels against dsDNA and levels of the soluble receptor IL-2 (sIL-2R) in serum. Conversely, no relationship was revealed between values of IL-10 and values of C3 and C4 complement components, IL-1, IL-2, IL-6, sIL-6R, TNF-alpha, sTNFR-alpha and INF-gamma. CONCLUSIONS: Elevated IL-10 serum levels in patients with SLE did not have, with the exception of the index of clinical activity of the disease, antibodies against dsDNA and sIL-2R any statistically significant relations to laboratory indicators of disease activity and levels of selected cytokines and their soluble receptors.
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The postoperative protein metabolism of 11 patients who had required either a colon conduit or ureterosigmoidostomy urinary diversion was examined. From the 3rd to 10th postoperative day day, each patient received a standard parenteral alimentation (100 g amino acids and 2000 kcal/24 h). Nitrogen balance, plasma level of the free amino acids, and the C3c-, C4-complement and transferrin fraction in plasma were determined regularly. The results showed that this substitution therapy succeeded in avoiding serious alterations in the parameters measured.