Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “complementation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed1984

Interallelic complementation in an inborn error of metabolism: genetic heterogeneity in argininosuccinate lyase deficiency.

We used complementation analysis as a probe for the detection of genetic heterogeneity within a single locus affected in a human disease, argininosuccinate lyase (L-argininosuccinate arginine-lyase, EC 4.3.2.1) deficiency. Fibroblasts cultured from 28 unrelated patients were fused in all possible pairwise combinations, and the argininosuccinate lyase activity in heterokaryons was assayed by measuring the incorporation of 14C from L-[ureido-14C]citrulline into acid-precipitable material. Partial complementation was observed in fusions involving 20 of the 28 strains, with the lyase activity increasing from 2- to 10-fold. Thirteen of the mutants were identified by the complementation analysis as being phenotypically unique. Of the 20 complementing strains, 3 were remarkable because they participated in all but 2 of the 32 positive complementation tests; 2 others constituted a unique subgroup that produced the highest increases in argininosuccinate lyase activity of all fusions. The 8 strains that did not complement any others consisted of two types: 3 mutants with the highest residual argininosuccinate lyase activity of all strains and 5 mutants with low residual activity. All of the mutants mapped to a single major complementation group. The data could be summarized as a circular complementation map with an attached linear tail, the mutants being distributed among 12 subgroups in a complex pattern. We conclude that all of these mutants are affected at a single locus, that extensive genetic heterogeneity is present in the mutant population, and that the affected locus in argininosuccinate lyase deficiency is likely to be the structural gene coding for that enzyme.

Alleles↗
PubMed2004

Strategies developed by bacteria and virus for protection from the human complement system.

The complement system is an important part of innate immunity providing immediate protection against pathogens without a need for previous exposure. Its importance is clearly shown by the fact that patients lacking complement components suffer from fulminant and recurring infections. Complement is an explosive cascade, and in order to control it there are inhibitors present on every human cell and also circulating in blood. However, many infectious agents have developed strategies to prevent clearance and destruction by complement. Some pathogens simply hijack the host's complement inhibitors, while others are able to produce their own homologues of human inhibitors. Knowledge of these mechanisms on a molecular level may aid development of vaccines and novel therapeutic strategies that would be more specific than the use of antibiotics that, apart from causing resistance problems, also affect the normal flora, the outcome of which could be devastating. In this study the structural requirements and functional consequences of interactions between the major soluble inhibitor of complement C4b-binding protein and Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes, Escherichia coli K1, Moraxella catarrhalis and Candida albicans are described. Furthermore, a novel inhibitor produced by Kaposi's sarcoma-associated herpesvirus is identified and characterized in detail: KCP. It is shown that KCP inhibits classical C3-convertase and presents activated complement factors C4b and C3b for destruction by a serine proteinase, factor I. Using molecular modelling and site-directed mutagenesis, it was possible to localize sites on the surface of KCP required for complement inhibition and it is concluded that KCP uses molecular mechanisms identical to human inhibitors.

Awards and Prizes↗
PubMed1962

The localization of in vivo bound complement in tissue section.

A technique has been described for the demonstration of a human complement component by an immunofluorescent method. The component detected is beta(1C)-globulin, a moiety of the third complement component, which has previously been obtained in pure form and to which a specific antiserum has been prepared. It has been shown in a model system that the binding of beta(1C)-globulin as shown by immunofluorescence is strictly equivalent to complement fixation as assessed by standard serological methods. This technique has been applied to the detection of in vivo bound complement in pathological human tissues. It was found that in vivo complement binding occurs in the lesions of several human diseases, but not elsewhere in the same tissues. In a rather limited survey of diseases that has been carried out, in vivo complement binding was found particularly in systemic L.E., various nephritides, and amyloidosis, as well as in single cases of some other diseases. The spectrum of in vivo complement binding has been compared with that of gamma-globulin binding (7S and 19S types) and with the demonstration of in vitro complement fixation and rheumatoid factor fixation. It was distinct from each of these. Rheumatoid factor fixation, detected by anti-19S antiserum showed promise as a method for the detection of antigen-antibody complexes and aggregated gamma-globulin in tissue sections. The interpretation of these findings in regard to the nature of the binding sites, and their possible significance in regard to pathogenic mechanisms have been discussed.

Antigen-Antibody Complex↗
PubMed1968

Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes.

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation. Preheating serum, incubating at 0 degrees C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species. The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000-30,000) and as such different from previously scribed C' system-derived chemotactic factors. These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components.

Animals↗
PubMed1979

Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages.

We have examined the Fc- and complement-receptor function of resident and thioglycollate-elicited mouse peritoneal macrophages plated on surfaces coated with rabbit antibody-antigen complexes and with complement. We derive four major conclusions from these studies. (a) The trypsin-resistant Fc receptors of resident and thioglycollate-elicited macrophages are completely modulated when these cells are plated on rabbit antibody-antigen complexes. Residual Fc receptor activity is a result of the incomplete modulation of trypsin-sensitive IgG2a receptors. (b) The complement receptors of thioglycollate-elicited macrophages, but not of resident macrophages, are modulated when these cells are plated on complement-coated surfaces. The capacity of the two cell types to modulate their complement receptors is correlated with their ability to ingest complement-coated erythrocytes. (c) The complement and Fc receptors of both types of macrophages move independently of one another. (d) Complement masks the Fc segments of IgG in immune complexes thereby rendering them ineffective as ligands for macrophage Fc receptors.

Animals↗
PubMed2002

Complement activation induced by purified Neisseria meningitidis lipopolysaccharide (LPS), outer membrane vesicles, whole bacteria, and an LPS-free mutant.

Complement activation is closely associated with plasma endotoxin levels in patients with meningococcal infections. This study assessed complement activation induced by purified Neisseria meningitidis lipopolysaccharide (Nm-LPS), native outer membrane vesicles (nOMVs), LPS-depleted outer membrane vesicles (dOMVs), wild-type meningococci, and an LPS-free mutant (lpxA(-)) from the same strain (44/76) in whole blood anticoagulated with the recombinant hirudin analogue. Complement activation products (C1rs-C1 inhibitor complexes, C4d, C3bBbP, and terminal SC5b-9 complex) were measured by double-antibody EIAs. Nm-LPS was a weak complement activator. Complement activation increased with preparations containing nOMVs, dOMVs, and wild-type bacteria at constant LPS concentrations. With the same protein concentration, complement activation induced by nOMVs, dOMVs, and the LPS-free mutant was equal. The massive complement activation observed in patients with fulminant meningococcal septicemia is, presumably, an indirect effect of the massive endotoxemia. Outer membrane proteins may be more potent complement activators than meningococcal LPSs.

Bacterial Outer Membrane Proteins↗
PubMed1995

Interallelic complementation of beta-subunit defects in fibroblasts of patients with propionyl-CoA carboxylase deficiency microinjected with mutant cDNA constructs.

Propionic acidemia results from deficiency of propionyl-CoA carboxylase (PCC) activity. PCC is a biotin-dependent, mitochondrial enzyme composed of alpha- and beta-subunits (structure, alpha 4 beta 4), with the alpha-subunit containing the biotin ligand. About two-thirds of fibroblast lines from patients with mutations in the PCCB (beta-subunit) gene show interallelic complementation in cell fusion experiments (the pccB and pccC subgroups of the pccBC major group defining beta-subunit mutations, where pccB x pccC fusions show complementation). We previously identified the mutations in several pccB or pccC cell lines and suggested that point mutations or small, in-frame insertions or deletions were likely responsible for the complementation obtained between beta-subunit defects. To test this hypothesis, we have introduced five different mutations (three pccB and two pccC) that fit these criteria into a PCC beta-subunit cDNA plasmid expressed from a cytomegalovirus promoter. The cDNA plasmids were microinjected into mutant fibroblasts and the cells were assayed by radioautographic detection of 14C-propionate incorporation into cellular macromolecules. Four different mutations (Pro228Leu or dupKICK140 from pccB or delta IIe408 or Arg410Trp from pccC) complemented cells from complementation subgroups in a pattern congruent with the results obtained in cell fusion experiments. The fifth mutation, Arg536Asn, which was found both in a complementing pccB and a non-complementing pccBC cell line, failed to complement any of the mutant cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization.

Glycoprotein gC1 of herpes simplex virus type 1 (HSV-1) binds complement component C3b. To determine if gC1 modifies the interaction of complement with virus-infected cells or cell-free virus, ns-1, a mutant HSV-1 strain that does not express gC1 at the cell surface and does not bind C3b, was compared with its parental strain, NS. Cells infected with the gC1 mutant were more susceptible to cytolysis mediated by antibody and complement or complement alone. The gC1 or gD1 genes were expressed in mammalian cells under the control of an inducible promoter. Cells induced to express gC1 resisted complement cytolysis, while cells expressing gD1 did not. gC1 modified cytolysis of virus-infected or -transfected cells by blocking alternative complement pathway activation. gC1 also modified complement-dependent virus neutralization, which was mediated by inhibiting the classical complement pathway. These results indicate a protective role for gC1 on the virion and at the cell surface.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1995

Complement-mediated bactericidal activity of human antibodies to poly alpha 2-->8 N-acetylneuraminic acid, the capsular polysaccharide of Neisseria meningitidis serogroup B.

Serum antibodies to Neisseria meningitidis group B (MenB) polysaccharide are reported not to elicit bacteriolysis in the presence of human complement. To reexamine this question, we evaluated the ability of two human IgM anti-MenB polysaccharide monoclonal antibodies (MAbs) and seven human MenB polysaccharide-reactive human IgM paraproteins to elicit bacteriolysis. In the presence of human complement, both MAbs and five of the seven paraproteins were bactericidal at antibody concentrations of 0.25-9.6 micrograms/mL (50% killing). Activity of the respective antibodies was enhanced 200- to > 10,000-fold when rabbit complement was used instead of human complement. With rabbit complement, the bactericidal activity of human IgM polyclonal antibody or MAb to Haemophilus influenzae type b (Hib) polysaccharide but not human IgG polyclonal antibody or MAb to Hib polysaccharide was similarly augmented. Thus, for both MenB and Hib, IgM antipolysaccharide antibodies elicit complement-mediated bactericidal activity in the presence of human complement, and the use of rabbit complement yields spuriously high activity.

Animals↗
PubMed1999

Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability.

Although complement activation appears to have an important role both in the early and late phases of atherosclerosis, the exact mechanism of the initiation of this activation is still unknown. Since injuries of the endothelial cells are known to result in increased stress-protein expression we tested the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system in normal human serum in a dose-dependent manner. Activation took place through the classical pathway. The lack of complement activation in agammaglobulinemic serum indicates that the classical pathway is triggered by anti-hsp60 antibodies. Hsp60 activated complement in the sera of 74 patients with coronary heart disease as well, and a strong positive correlation (r = 0.459, P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the level of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: binding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa. Our present findings indicate that anti-hsp60 and anti-hsp65 antibodies are distinct, showing only partial cross-reactivity. Since complement activation plays an important role in the development of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present findings may have important pathological implications.

Adult↗
PubMed1992

Antibodies and complement enhance binding and uptake of HIV-1 by human monocytes.

OBJECTIVE: To characterize antibody- and complement-mediated binding and uptake of HIV-1 by human monocytes. DESIGN: The first step in the infection of the monocyte by HIV-1 is binding of the virus to the susceptible cell. Procedures were designed to assess the influence of anti-HIV-1 antibodies and complement on this binding, and to study the process of internalization following binding. METHODS: Human monocytes were incubated with fluorescein-labelled purified HTLV-IIIB virions and human sera with high-titre anti-HIV-1 antibodies and/or complement. Binding and uptake of virus by the monocytes was measured as fluorescence per cell by flow cytometry. RESULTS: Binding of purified HIV-1 to monocytes was increased by complement and, to a lesser extent, by anti-HIV-1 antibodies. Uptake of HIV-1 bound to the monocyte appeared to be mediated by antibodies and was increased further by the presence of complement. Complement alone, however, resulted in the uptake of only a small part of the bound virus. CONCLUSIONS: Complement significantly increases the binding of HIV-1 to human monocytes, and a combination of antibodies and complement efficiently mediates uptake of HIV-1 by monocytes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Complement activation in patients undergoing mechanical circulatory support.

Contact of blood with artificial surfaces activates pro-inflammatory responses and the complement cascade. This may have broad implications on the post implantation fate of patients needing mechanical circulatory support. Therefore, we investigated the course and prognostic value of complement factors C3a and C5a in 66 patients supported with pulsatile ventricular assist devices. All patients were in severe cardiogenic shock, i.e., catecholamine dependent and in the intensive care unit, before implementation of mechanical circulatory support. Isolated left ventricular support (Novacor [Oakland, CA] or Thermo Cardiosystems, Inc. [TCI; Woburn, MA]) was used in 28 patients, and biventricular support (Berlin Heart [Mediport, Berlin, Germany]) in 38 patients. Before initiation of mechanical circulatory support, no statistically significant differences in C3a or C5a between surviving and nonsurviving patients with left ventricular assist devices (LVADs) were found. Patients with biventricular assist devices (BVADs) had significantly higher C3a (804 +/- 364 ng/L) levels than patients with LVADs (536 +/- 204 ng/L, p = 0.02) before mechanical circulatory support. Only C5a, only in the BVAD group, was able to predict patients' post implantation course before implantation of a ventricular assist device (p = 0.02). Three weeks after initiation of mechanical circulatory support, complement factors remained increased in all groups. There was no difference, however, in complement activation between patients with LVADs and those with BVADs. Patients not reaching transplantation had significantly higher C3a levels at this point than those successfully supported (p = 0.007). The degree of complement activation mainly depends on the severity of cardiogenic shock before initiation of mechanical circulatory support, and not on the device used. Patients with extremely high levels of complement activation before implantation of the device could be saved with BVAD rather than LVAD support. Patients who continued to have highly elevated complement levels 3 weeks after initiation of mechanical circulatory support had unfavorable prognoses. Complement activation indicates the severity of cardiogenic shock before implementation of mechanical circulatory support and the degree of recovery from secondary organ dysfunction while on the device. It is fairly independent of the system used for mechanical circulatory support, and therefore can be applied to predict patients' post implantation course and outcome.

Adolescent↗
PubMed1975

Differences in the sensitivity of tumor cells and normal lymphocytes toward lysis by alloantibodies and guinea pig or rabbit complement.

Antisera produced against sarcoma I (SaI) cells in C57BL/6 and CBA mice tested for their cytotoxic activity against normal A lymphocytes and SaI tumor cells, using guinea pig or rabbit complement. Whereas high levels of cytotoxic activity against normal A lymphocytes were revealed with both antisera using either complement, only rabbit complement produced significant lysis of tumor cells under the standard conditions of the cytotoxic test (30 min, 37 C). However, upon prolonged incubation, guinea pig complement also produced high levels of lysis of SaI cells with the C57BL anti-SaI, but not with the CBA anti-SaI serum. Because these two antisera contain antibodies directed mainly against the H-2K and H-2D specificities, respectively, these results seemed to suggest that SaI cells are lysed in the presence of guinea pig complement with anti-H-2K antibodies but not with anti-H-2D antibodies. This conclusion was further supported by the use of antisera of restricted specificity prepared by selective absorption of the C57BL anti-SaI serum with CBA or DBA/2 cells. However, a C57BL anti-A serum which did not contain antibodies capable of lysing SaI target cells on prolonged incubation with guinea pig complement did not inhibit their subsequent lysis with the C57BL anti-SaI serum. These findings might suggest that under these modified conditions, mainly tumor-specific antigen-antibody systems are revealed with guinea pig complement, whereas with rabbit complement, under the standard conditions of the cytotoxic test, all antigen-antibody systems are detected.

Absorption↗
PubMed1981

Complement-dependent and independent mechanisms in acute antibody-mediated rejection of skin xenografts in the mouse.

Complement dependency of acute antibody-mediated rejection (AAR) was studied in a xenogeneic skin graft model in the mouse. PVG/c rat skin grafted to immunosuppressed mice was acutely destroyed by i.v. administered mouse anti-rat serum on day 7 after grafting. Depression of the hemolytic complement titer in the recipients was indicative for complement consumption during the rejection process. Complete and long-lasting complement depletion induced by treatment with cobra venom factor (COVF) decreased the sensitivity of the grafts to AAR. However, complete protection was not achieved, since high doses of antidonor serum again induced destruction. Similar results were obtained in C5-deficient recipients and in COVF-treated C5-deficient recipients. These results indicated that complement-independent rejection mechanisms were operative. This was further substantiated by the finding that purified noncomplement-fixing IgC1 subclass antibodies were able to elicit mice with a normal complement status was caused by intravascular coagulation without primary involvement of polymorphonuclear leukocytes. In complement-depleted animals an Arthus-like reaction was seen, with dense intravascular accumulation of polymorphonuclear leukocytes (PMNs) that, apparently, were attracted to the graft through complement-independent mechanisms.

Animals↗
PubMed2000

A recombinant soluble chimeric complement inhibitor composed of human CD46 and CD55 reduces acute cardiac tissue injury in models of pig-to-human heart transplantation.

BACKGROUND: Inasmuch as complement plays a critical role in many pathological processes and in xenograft rejection, efficient complement inhibitors are of great interest. Because the membrane-associated complement inhibitors are very effective, recombinant soluble molecules have been generated. METHODS: We tested the efficacy of complement activation blocker-2 (CAB-2), a recombinant soluble chimeric protein derived from human decay accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), in two models of pig-to-human xenotransplantation in which tissue injury is complement mediated. The in vitro model consisted of porcine aortic endothelial cells and human serum, and the ex vivo model consisted of a porcine heart perfused with human blood. RESULTS: In vitro, addition of CAB-2 to serum inhibited cytotoxicity and the deposition of C4b and iC3b on the endothelial cells. Ex vivo, addition of CAB-2 to human blood prolonged organ survival from 17.3 +/- 6.4 min in controls to 108 +/- 55.6 min with 910 nM (100 microg/ml) CAB-2 and 219.8 +/- 62.7 min with 1820 nM (200 microg/ml) CAB-2. CAB-2 also retarded the onset of increased coronary vascular resistance. The complement activity of the perfusate was reduced by CAB-2, as was the generation of C3a and SC5b-9. The myocardial tissues had similar deposition of IgG, IgM, and Clq; however, CAB-2 reduced the deposition of C3, C4, and C9. Hearts surviving >240 min demonstrated trace to no deposition of C9 and normal histologic architecture. CONCLUSION: These results indicate that CAB-2 can function as an inhibitor of complement activation and markedly reduce tissue injury in models of pig-to-human xenotransplantation and thus may represent a useful therapeutic agent for xenotransplantation and other complement-mediated conditions.

Animals↗
PubMed2003

Excessive matrix accumulation in the kidneys of MRL/lpr lupus mice is dependent on complement activation.

Complement receptor 1-related gene/protein y (Crry) in rodents is a potent membrane complement regulator that inhibits complement C3 activation by both classical and alternative pathways. Complement inhibition with Crry as the recombinant protein Crry-Ig has been demonstrated to prevent MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) mice from developing proteinuria and renal failure. Crry-Ig-treated mice also showed less glomerulosclerosis compared with control MRL/lpr mice. To clarify how complement inhibition with Crry might affect renal scarring in lupus nephritis, gene transcript profiling was performed comparing Crry-Ig-treated MRL/lpr mice to control-treated MRL/lpr mice as well as to the MRL/+ strain control. Altered gene expression was confirmed by quantitative PCR, and protein quantity with either immunoblotting or immunofluorescence microscopy. Collagens I, III, IV, and VI were overexpressed in control MRL/lpr mice, whereas complement inhibition with Crry reduced the overexpression of these extracellular matrix components toward normal. Plasminogen activator inhibitor 1, connective tissue growth factor, and TGF-beta1 were upregulated in MRL/lpr mice compared with MRL/+ mice and were normalized by Crry-Ig treatment, suggesting that the product of these genes may contribute to the progressive glomerulosclerosis in MRL/lpr mice in a complement-dependent fashion. Thus, complement inhibition with Crry has a prominent effect on matrix-related genes and proteins, which translates into improvement in functional renal disease.

Animals↗
PubMed2006

Anti-alphaGal-dependent complement-mediated cytotoxicity in metastatic melanoma.

Antibodies to the cell surface disaccharide galactose(alpha1,3)galactose (alphaGal) are the most prevalent natural antibodies in human serum. The anti-alphaGal immunoglobulin M-dependent activation of complement causes hyperacute rejection of organ transplants from discordant species by human recipients. It has been shown in vitro that human tumour cells transduced with the gene that synthesizes alphaGal become sensitive to human serum. A prerequisite for anti-alphaGal antibody-based therapeutic strategies is that patients with cancer have adequate serum levels of anti-alphaGal immunoglobulins and complement. The objective of this work was to measure the levels and function of anti-alphaGal immunoglobulins and complement in the serum of patients with metastatic melanoma and healthy volunteers. Serum complement levels were assayed by radial immunodiffusion. Anti-alphaGal immunoglobulin G and immunoglobulin M titres were measured by enzyme-linked immunosorbent assay. Disaccharide sugar blocking was used to investigate antibody specificity. The functional integrity of anti-alphaGal antibodies and complement was investigated in cell lysis assays. It was found that the levels of the complement components C1q, C3 and C4 and the function of the classical complement pathway were normal in metastatic melanoma patients. Anti-alphaGal antibody titres were as variable in metastatic melanoma patients as in healthy controls, and the lysis of alphaGal-expressing cells correlated with anti-alphaGal immunoglobulin M titre (P < 0.0001). Anti-alphaGal antibody titres, complement levels and overall cytolytic function in the serum of patients with metastatic melanoma were indistinguishable from those of healthy controls. There is thus nothing intrinsic to the disease that will limit anti-alphaGal-based therapeutic strategies for enhanced antigen presentation or induced cell lysis, including the mimicry of hyperacute rejection.

Adult↗
PubMed1995

Role of complement in renal tubular damage.

Deposition of immunoglobulins, complement proteins C1q, C3c, C3d, C4, C5, C6, C7, C8, C9, and terminal complement complex neoantigens in the renal tubulointerstitium was studied in serial sections by immunofluorescence microscopy. Renal tissue from 45 cases with various glomerular diseases, including 8 controls, was studied. The patients were divided into groups; one with tubulointerstitial lesions (24 cases) and the other without (13 cases). The immunoproteins were deposited mainly in the tubular basement membrane and blood vessels. Compared with controls there was a significantly increased staining score for C5 to C9 in the tubular basement membrane in both disease groups. However, the increase in terminal complement complex neoantigens score was significant only in the disease group with tubulo interstitial lesions. The changes in C3d score were not significant. Serial sections showed consistent and heavy ribbon-like deposits of complement proteins C3d, C5 to C9, and terminal complement complex neoantigens in corresponding locations of the segments of tubular basement membrane, mainly in the disease group with tubulointerstitial lesions and especially in the damaged tubules. These findings suggest that in situ activation of the complement cascade leads to the deposition of terminal complement complex neoantigens. Complement activation in the basal area of the tubules may, therefore, be an important pathogenetic mechanism in tubulointerstitial damage.

Basement Membrane↗