RESUMO
Primary pneumococcal peritonitis is a rare infection that has been described in women but has not been previously linked with immunodeficiency. The complement system plays a central role in immune defence against Streptococcus pneumoniae and, in order to evade complement attack, pneumococci have evolved a large number of mechanisms that limit complement-mediated opsonization and subsequent phagocytosis. We investigated an apparently immunocompetent woman with primary pneumococcal peritonitis and identified a family with deficiency for complement factor I. Primary pneumococcal peritonitis should be considered a possible primary immunodeficiency presentation.
Assuntos
Complemento C3/deficiência , Doenças da Deficiência Hereditária de Complemento/imunologia , Peritonite/imunologia , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Complemento C3/imunologia , Feminino , Doenças da Deficiência Hereditária de Complemento/patologia , Humanos , Peritonite/patologia , Infecções Pneumocócicas/patologiaRESUMO
In this paper we have extended our earlier studies of the action of increasing Factor I concentration on complement activation by using a soluble activator, lipopolysaccharide (LPS) endotoxin, and using human erythrocytes as a source of CR1 - the co-factor needed for the final clip of iC3b to C3dg by Factor I. Using this more physiological system, the results show that we can predict that a quite modest increase in Factor I concentration - 22 µg/ml of extra Factor I - will convert the activity of the highest risk sera to those of the lowest risk. Preliminary experiments have been performed with erythrocytes allotyped for CR1 number. While we have not been able to perform an adequate study of their co-factor activities in our assays, preliminary experiments suggest that when Factor I levels are increased the difference produced by different allotypes of red cells is largely overcome. This suggests that in patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with eculizumab, additional treatment with Factor I may be very useful in reducing the need for blood transfusion. We have also explored the age-related allele frequency for the two polymorphisms of Factor H and the polymorphism of C3. In our population, unlike the 1975 study, we found no age variation in the allele frequency in these polymorphisms. This may, however, reflect that the Cambridge BioResource volunteers do not include many very young or very elderly patients, and in general comprise a population not greatly at risk of death from infectious disease.
Assuntos
Complemento C3b/metabolismo , Fator H do Complemento/genética , Fator I do Complemento/imunologia , Eritrócitos/imunologia , Hemoglobinúria Paroxística/sangue , Receptores de Complemento 3b/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Complemento C3b/genética , Fator I do Complemento/análise , Regulação para Baixo , Frequência do Gene , Hemoglobinúria Paroxística/terapia , Humanos , Soros Imunes/metabolismo , Lipopolissacarídeos/imunologia , Pessoa de Meia-Idade , Polimorfismo Genético , Adulto JovemRESUMO
Sera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that influence predisposition to age-related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low-risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down-regulation. Because iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation, the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement-induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic aid for down-regulating hyperactivity of the C3b feedback cycle, thereby providing a treatment for age-related macular degeneration and other inflammatory diseases of later life.
Assuntos
Complemento C3b/imunologia , Via Alternativa do Complemento/efeitos dos fármacos , Fibrinogênio/farmacologia , Regulação da Expressão Gênica/imunologia , Fragmentos de Peptídeos/imunologia , Alelos , Complemento C3b/genética , Fator H do Complemento/genética , Fator H do Complemento/imunologia , Retroalimentação Fisiológica , Fibrinogênio/imunologia , Genótipo , Heterozigoto , Homozigoto , Humanos , Fragmentos de Peptídeos/genética , Polimorfismo de Nucleotídeo Único , Zimosan/farmacologiaRESUMO
Fifty years ago several thousand children were born with severe limb defects after their mothers had been given thalidomide in pregnancy. This tragedy caused procedures for licensing new medicines to become much stricter. Where, nevertheless, significant side effects were found it became common to sue for damages. These consequences have caused possibly an even greater disaster damaging many more people and threatening ruin to health services everywhere. The huge increase in both time and cost in bringing medicines to market is increasing their price to unsupportable levels; and only wealthy companies are now able to do so. This requires reform as does litigation for 'statistical' harmful effects.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Licenciamento/economia , Efeitos Tardios da Exposição Pré-Natal , Retirada de Medicamento Baseada em Segurança , Talidomida/efeitos adversos , Animais , Criança , Custos de Medicamentos/tendências , Feminino , Humanos , Jurisprudência , Masculino , Gravidez , Talidomida/economia , Talidomida/normasRESUMO
To conserve full complement activity, a number of precautions need to be taken in preparing serum. This is particularly the case with mouse complement where the classical pathway is notoriously unstable.
Assuntos
Proteínas Sanguíneas/metabolismo , Proteínas do Sistema Complemento/metabolismo , Testes Imunológicos de Citotoxicidade/métodos , Animais , Proteínas Sanguíneas/imunologia , Via Clássica do Complemento , Proteínas do Sistema Complemento/imunologia , Erros de Diagnóstico/prevenção & controle , Diretrizes para o Planejamento em Saúde , Camundongos , Estabilidade Proteica , Reprodutibilidade dos Testes , Soro/metabolismo , Manejo de EspécimesRESUMO
Complement has been studied for over a century and its role in promoting the effector side of antibody-mediated immune reactions and of inducing inflammation is well understood. Nevertheless, it has proved surprisingly difficult to translate this information into pharmaceutical agents that can be used to treat immunopathological and inflammatory disease. There are, however, now clear signs that this situation will change. New types of therapeutic agents to interfere with complement function are being developed and it has become apparent quite recently that some common and otherwise untreatable diseases such as age-related macular degeneration are very largely due to mutations in the complement system that leads to a hyperinflammatory state. This has stimulated a renaissance of interest in the complement system as a therapeutic target and in this short review we discuss the possible ways of taking complement to the clinic, and the indications for which this may be carried out.
Assuntos
Proteínas do Sistema Complemento/fisiologia , Animais , HumanosRESUMO
SIC (streptococcal inhibitor of complement) is a 31 kDa protein secreted by a few highly virulent strains of GAS (group A streptococci), predominantly by the M1 strain. Initially described as an inhibitor of the membrane attack complex of complement, it has turned out to be a polyfunctional inhibitor of the innate mucosal immune response. The SIC protein sequence contains three domains: an N-terminal SRR (short repeat region), followed by three longer tandem repeats [LRR (long repeat region)] and a C-terminal PRR (proline-rich region). SIC inhibits the antibacterial activity of a wide range of antimicrobial peptides and proteins: i.e. lysozyme, SLPI (secretory leucocyte proteinase inhibitor), LL-37, hNP-1 (human neutrophil peptide-1) and the human beta-defensins 1, 2 and 3. Analysis of the functional properties of recombinant domains of SIC shows that binding and inhibition of lysozyme and human beta-defensin-3 require the SRR+LRR, as does binding to SLPI. Complement inhibition is confined to the SRR. M12 GAS secrete a protein 'distantly related to SIC' (DRS). DRS contains a C-terminal PRR which is significantly similar to that of SIC, but it has no central LRR and the N-terminal SRR is very different. DRS inhibits human beta-defensin-3, but has no effect on lysozyme, SLPI or complement.
Assuntos
Antibacterianos/antagonistas & inibidores , Proteínas Inativadoras do Complemento/metabolismo , Proteínas Inativadoras do Complemento/farmacologia , Streptococcus/classificação , Streptococcus/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Humanos , Ligação Proteica , beta-Defensinas/metabolismoRESUMO
Antimicrobial molecules are ancient and essential small cationic molecules of the host defence system which are found in a wide variety of species. They display antimicrobial activity against a wide range of bacteria, fungi and viruses, an activity that has been mostly attributed to the disruption of microbial membranes. In this article, we will review the "classical" functions of 3 classes of antimicrobial molecules, namely defensins, cathelicidins, and the four-disulfide core proteins secretory leukocyte proteinase inhibitor (SLPI) and elafin. In addition to the study of their expression in a variety of cell types and the regulation of their production, we will also describe novel properties of these molecules that have been highlighted by recent studies. These include their ability to chemoattract a variety of inflammatory, immune and other cell types (neutrophils, macrophages, monocytes, lymphocytes, mast cells, epithelial cells) in vitro and in vivo. In addition, we will discuss the potential use of these newly discovered properties for therapeutic or vaccination purposes, using protein- or gene-transfer based methodologies. Finally, we will examine in an extensive fashion the strategies used by microorganisms to circumvent and subvert host defence mechanisms, such as the modifications of cell membranes and walls, the secretion of inactivating proteins and proteases and the down-regulation of expression of antimicrobial molecules. Increased understanding of the mechanisms used by both the host and the microbes to 'win the battle' may ultimately lead to new therapeutic strategies aimed to treat infectious diseases.
Assuntos
Anti-Infecciosos/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Células Epiteliais/imunologia , Imunidade/imunologia , Inflamação/imunologia , Inflamação/terapia , Sequência de Aminoácidos , Animais , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
In this study we have optimised the enzyme immunoassay (ELISA) to quantify CD59 antigen in human serum or plasma. The glycosyl-phosphatidylinositol (GPI)-linked form of CD59 is known to complex with serum high-density lipoprotein. For ELISA optimisation, therefore, we investigated the effect of detergents, added to the sample diluent, on the determined values of CD59. Values obtained in the presence of octyl-glucoside (OG) for 20 adults aged 18-35 years and 17 children 1-5 years old were, respectively, 33-119 ng/ml (mean +/- S.D.: 66+/-22 ng/ml) and 37-143 ng/ml (76+/-33 ng/ml). These results were higher than those measured without OG and were in contrast with published results showing absence, or eight to nine times lower levels, of the protein in serum. A known range for serum concentrations of CD59 in healthy individuals will establish an important reference point for clinical work and for the investigation of diseases involving the complement membrane attack complex (MAC) and its regulation.
Assuntos
Antígenos CD59/sangue , Antígenos CD59/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Glucosídeos/química , Glicosilfosfatidilinositóis/metabolismo , Adolescente , Adulto , Antígenos CD59/química , Antígenos CD59/imunologia , Pré-Escolar , Glicosilfosfatidilinositóis/química , Humanos , Lactente , Octoxinol , Polietilenoglicóis/químicaRESUMO
The dominant autoantigen in SLE is the nucleosome and immune complexes involving nucleosomes are the major cause of tissue damage. Nucleosomes can be broken down in vivo with Desoxyribonuclease 1. DNase 1 from humans and mice is inhibited by actin and it is proposed that the release of platelet actin at inflammatory sites is one mechanism which causes nucleosomes to become antigenic. Rats whose DNase 1 is not inhibited by actin do not get lupus. Treatment of NZB/W mice with recombinant DNase slows the onset of their disease if given early and improves the renal disease if given later. This disease can also be entirely prevented by treatment with dexamethasone. Mice whose DNase 1 gene is knocked out are known to develop lupus and to be otherwise normal. DNase 1 especially in its mutant actin and salt resistant forms remains an attractive candidate for the treatment of SLE.
Assuntos
Desoxirribonucleases/genética , Lúpus Eritematoso Sistêmico/imunologia , Desoxirribonucleases/deficiência , Desoxirribonucleases/uso terapêutico , Terapia Genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/terapiaRESUMO
OBJECTIVES: To estimate exposures to cadmium (Cd) received by the United Kingdom population as a result of the dispersion of zinc Cd sulfide (ZnCdS) by the Ministry of Defence between 1953 and 1964, as a simulator of biological warfare agents. METHODS: A retrospective risk assessment study was carried out on the United Kingdom population during the period 1953-64. This determined land and air dispersion of ZnCdS over most of the United Kingdom, inhalation exposure of the United Kingdom population, soil contamination, and risks to personnel operating equipment that dispersed ZnCdS. RESULTS: About 4600 kg ZnCdS were dispersed from aircraft and ships, at times when the prevailing winds would allow large areas of the country to be covered. Cadmium released from 44 long range trials for which data are available, and extrapolated to a total of 76 trials to allow for trials with incomplete information, is about 1.2% of the estimated total release of Cd into the atmosphere over the same period. "Worst case" estimates are 10 microg Cd inhaled over 8 years, equivalent to Cd inhaled in an urban environment in 12100 days, or from smoking 100 cigarettes. A further 250 kg ZnCdS was dispersed from the land based sites, but significant soil contamination occurred only in limited areas, which were and have remained uninhabited. Of the four personnel involved in the dispersion procedures (who were probably exposed to much higher concentrations of Cd than people on the ground), none are suspected of having related illnesses. CONCLUSION: Exposure to Cd from dissemination of ZnCdS during the "cold war" should not have resulted in adverse health effects in the United Kingdom population.
Assuntos
Cádmio/análise , Exposição Ambiental/análise , Poluição do Ar/estatística & dados numéricos , Guerra Biológica , Cádmio/efeitos adversos , Exposição Ambiental/efeitos adversos , Humanos , Características de Residência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sulfetos/efeitos adversos , Sulfetos/análise , Reino Unido , Compostos de Zinco/efeitos adversos , Compostos de Zinco/análiseRESUMO
After ingestion by mosquitoes, gametocytes of malaria parasites become activated and form extracellular gametes that are no longer protected by the red blood cell membrane against immune effectors of host blood. We have studied the action of complement on Plasmodium developmental stages in the mosquito blood meal using the rodent malaria parasite Plasmodium berghei and rat complement as a model. We have shown that in the mosquito midgut, rat complement components necessary to initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are present for several hours following ingestion of P. berghei-infected rat blood. In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement exposure during the first 3 h of development. Subsequently, parasites became increasingly sensitive to complement lysis. To investigate the mechanisms involved in their protection, we tested for C3 deposition on parasite surfaces and whether host CD59 (a potent inhibitor of the complement membrane attack complex present on red blood cells) was taken up by gametes while emerging from the host cell. Between 0.5 and 22 h, 90% of Pbs21-positive parasites were positive for C3. While rat red and white blood cells stained positive for CD59, Pbs21-positive parasites were negative for CD59. In addition, exposure of parasites to rat complement in the presence of anti-rat CD59 antibodies did not increase lysis. These data suggest that parasite or host molecules other than CD59 are responsible for the protection of malaria parasites against complement-mediated lysis. Ongoing research aims to identify these molecules.
Assuntos
Anopheles/imunologia , Complemento C3/imunologia , Complemento C5/imunologia , Plasmodium berghei/imunologia , Animais , Anopheles/parasitologia , Sistema Digestório/imunologia , Interações Hospedeiro-Parasita , Plasmodium berghei/crescimento & desenvolvimento , Ratos , Ratos WistarRESUMO
Streptococcal inhibitor of complement (SIC) was first described in 1996 as a putative inhibitor of the membrane attack complex of complement (MAC). SIC is a 31 000 MW protein secreted in large quantities by the virulent Streptococcus pyogenes strains M1 and M57, and is encoded by a gene which is extremely variable. In order to study further the interactions of SIC with the MAC, we have made a recombinant form of SIC (rSIC) in Escherichia coli and purified native M1 SIC which was used to raise a polyclonal antibody. SIC prevented reactive lysis of guinea pig erythrocytes by the MAC at a stage prior to C5b67 complexes binding to cell membranes, presumably by blocking the transiently expressed membrane insertion site on C7. The ability of SIC and clusterin (another putative fluid phase complement inhibitor) to inhibit complement lysis was compared, and found to be equally efficient. In parallel, by enzyme-linked immunosorbent assay both SIC and rSIC bound strongly to C5b67 and C5b678 complexes and to a lesser extent C5b-9, but only weakly to individual complement components. The implications of these data for virulence of SIC-positive streptococci are discussed, in light of the fact that Gram-positive organisms are already protected against complement lysis by the presence of their peptidoglycan cell walls. We speculate that MAC inhibition may not be the sole function of SIC.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas Inativadoras do Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Proteínas do Sistema Complemento/metabolismo , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Southern Blotting , Western Blotting , Membrana Celular/imunologia , Complemento C5/metabolismo , Complemento C7/metabolismo , Complemento C8/metabolismo , Proteínas Inativadoras do Complemento/isolamento & purificação , Proteínas Inativadoras do Complemento/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Proteínas Recombinantes/isolamento & purificação , Streptococcus pyogenes/classificação , Streptococcus pyogenes/imunologiaRESUMO
HIV-1 SF13 emerged in a patient with immunity to HIV-1 SF2. This study determined the effect of antibodies raised to HIV-1 SF2 on the replication of the later variant. Antisera in rats were raised previously to a complete set of overlapping, synthetic 15mer peptides following the sequence of HIV-1 SF2 gp120. These sera have now been used in neutralization and enhancement assays against viruses derived from molecular clones of both variants. The sets of peptides inducing neutralizing antibodies to the two variants overlap. Antibodies to the third variable region of HIV-1 SF2 only neutralize the homologous virus whereas those to the second and fourth variable regions neutralize both variants. In contrast, the sets of major epitopes involved in enhancement do not overlap. Epitopes for both variants form two clusters when superimposed on the conformation of the conserved regions. To determine if antibodies with the potential to enhance or neutralize HIV-1 SF2 change over time in infected individuals sera from chimpanzees were used because no material was still available from the original patient. Antibodies to HIV-1 SF2 neutralizing epitopes and HIV-1 SF13 enhancing epitopes were present in the circulation of chimpanzees infected with HIV-1 SF2. Once antibodies to the neutralizing epitopes were induced they persisted whereas antibodies to the enhancing epitopes varied with time after infection. Conditions may therefore exist within individual hosts where not only neutralizing but also enhancing antibodies have the potential to contribute to the selection pressure operating on the circulating population of polymorphic variants.
Assuntos
Anticorpos Facilitadores/imunologia , Epitopos/imunologia , Anticorpos Anti-HIV/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Animais , Anticorpos Facilitadores/genética , Epitopos/química , Variação Genética/imunologia , Proteína gp120 do Envelope de HIV/química , HIV-1/classificação , HIV-1/patogenicidade , Testes de Neutralização , Pan troglodytes , Fragmentos de Peptídeos/imunologia , Ratos , Ratos Endogâmicos , Sorotipagem , Replicação ViralAssuntos
Apoptose/imunologia , Doenças Autoimunes/imunologia , Proteínas do Sistema Complemento/deficiência , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Alelos , Animais , Formação de Anticorpos , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/genética , Viés , Proteínas de Transporte/genética , Criança , Pré-Escolar , Colectinas , Ativação do Complemento , Proteínas Inativadoras do Complemento 1/deficiência , Proteínas Inativadoras do Complemento 1/genética , Complemento C1q/deficiência , Complemento C1q/genética , Complemento C1q/imunologia , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/fisiologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Genótipo , Cobaias , Humanos , Lactente , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/genética , Masculino , Camundongos , Camundongos Endogâmicos MRL lpr , Camundongos Knockout , Camundongos Mutantes , Pessoa de Meia-Idade , Modelos Imunológicos , Polimorfismo Genético , Receptores de Complemento/química , Receptores de Complemento/genéticaRESUMO
The human IgA Fc receptor (FcalphaR, CD89) plays an important role in host defence against invading pathogens. To study the properties of the receptor, 12 MoAbs, namely, MIP7c, MIP8a, MIP9a, MIP10c, MIP11c, MIP14b, MIP15b, MIP38c, MIP59c, MIP65c, MIP68b and MIP71a, were generated. The inhibitory effects of the antibodies on FcalphaR functions were tested. Three of the antibodies, MIP7c, MIP8a and MIP59c, were able to block up to 90% of soluble FcalphaR binding to IgA-coated beads and 70-80% of neutrophil phagocytosis of IgA immune complexes (IC). MIP8a could also inhibit IgA IC-induced neutrophil lactoferrin release, while cross-linking of FcalphaR with MIP8a and anti-mouse IgG could elicit neutrophil lactoferrin release. However, IgA IC-induced lactoferrin release required both extracellular calcium and magnesium, whereas MIP8a-induced release did not require extracellular magnesium and only partially required extracellular calcium. In addition, the time course of IgA IC-induced lactoferrin release was slow. Lactoferrin was not detectable if the incubation time was less than 0.5 h. In contrast, MIP8a-induced lactoferrin release was fast. Lactoferrin could be detected within 5 min of incubation. Therefore, neutrophil lactoferrin release induced by IgA IC differed from that induced by cross-linking of FcalphaR with MIP8a.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Antígenos CD/metabolismo , Imunoglobulina A/metabolismo , Lactoferrina/metabolismo , Neutrófilos/metabolismo , Receptores Fc/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/genética , Antígenos CD/imunologia , Células CHO , Cálcio/metabolismo , Cátions Bivalentes , Cricetinae , Reagentes de Ligações Cruzadas , Humanos , Magnésio/metabolismo , Camundongos , Coelhos , Receptores Fc/genética , Receptores Fc/imunologia , Fatores de TempoRESUMO
BACKGROUND: It has previously been reported that patients with systemic lupus erythematosus (SLE) and glomerulonephritis do not have anti- (deoxyribonucleic acid) DNA antibodies in their urine. This finding was attributed to specific entrapment of anti-DNA antibodies by the immune complexes in the glomerular capillary walls. METHODS: This phenomenon has been re-investigated as part of a study of the use of desoxyribonuclease 1 (DNase 1) to treat lupus nephritis (LN). For this purpose an ELISA was developed for the detection of anti-DNA antibodies in urine. It was found that such an assay was very susceptible to the presence of DNase in urine which destroys the antigen coating the plates and gives rise to false negative results. For this reason, it is essential that all tests for anti-DNA antibodies in the urine are carried out in the presence of EDTA to inhibit the endogenous DNase 1 activity. RESULTS: Using this assay to test the urine from 24 patients with LN and non-selective proteinurea, it was found that they all contained anti-DNA antibodies. The amount of anti-DNA antibodies detected in the urine was compared with that expected by calculations from the anti-DNA antibody titre in the serum and total immunoglobulin levels in serum and in urine. It showed that in 20 patients there was neither specific entrapment nor specific excretion of anti-DNA in urine, only the expected amount of leakage. In only three patients was any appreciable entrapment demonstrated and in only one, any excess excretion. CONCLUSIONS: It is suggested that the failure to detect anti-DNA antibodies in the urine in the previous work was due to failure to inhibit the endogenous urinary DNase. It remains to be determined whether the retention of anti-DNA antibodies or excessive secretion is correlated with clinical phases of LN.