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Biomedical subjects

V Agnello

Publications and source records attributed to V Agnello.

At least 73 records · Page 4Linked to original sources
PubMed1977

Detection of immune complexes. The use of radioimmunoassays with Clq and monoclonal rheumatoid factor.

This study describes two sensitive, rapid, relatively simple, competitive inhibition radioimmunoassays for detecting immune complex. The tests are based on the inhibition of I125-Clq or I125-monoclonal rheumatoid factor (mRF) binding to an insoluble substrate, IgG-Sepharose. The assays can be performed in 5 h utilizing 10 micronl of serum. Heating of serum is not required and polyclonal rheumatoid factors do not interefere. With the two assays, a wide range of complexes of various size and complement fixing activity can be detected. The Clq test can detect complement fixing Ig complexes larger than 19S, while the mRF tests detect complexes of IgG as small as 8S irrespective of their complement fixing activity. Mouse, rabbit, and human aggregated IgG (agg IgG) can be detected in the Clq test, and human and rabbit agg IgG in the mRF test. As low as 4 microng/ml of isolated human agg IgG can be detected in the Clq test and 0.5 microng/ml in the rheumatoid factor test. Sensitivity is greater for mouse agg IgG. For pathologic sera which must be diluted to eliminate interfering factors, the sensitivity of the assay is approximately 10 times less. The Clq test showed marked inhibition by systemic lupus erythematosus sera with close correlation with CH50 levels and disease activity. The mRF test showed better correlation with rheumatoid arthritis sera. In addition, anionic macromolecules known to react with Clq and other Clq reactants that occur in pathologic sera such as the "low molecular weight" substances in systemic lupus erythematosus are also detected. These reactants are not detectable in the mRF test and can be eliminated in the Clq test by performing the test at higher ionic strength. The tests can be applied to the study of a variety of pathologic states where immune complexes appear to play a role.

Animals↗
PubMed1975

Hereditary C2 deficiency in systemic lupus erythematosus and acquired complement abnormalities in an unusual SLE-related syndrome.

Early study of kindreds with C2 deficiency indicated that absence of C2 had no detrimental effect on affected individuals. Studies of additional kindreds, however, show a high incidence of SLE and other connective tissue diseases among homozygous C2-deficient members. A group of patients with an unusual SLE-related syndrome is described. In common with certain SLE patients they have marked depression of early complement components and presence of circulating Clq precipitins. It is suggested that early complement components are involved in specific host defense mechanisms and deficiencies of these components may predispose to such diseases.

Antibodies, Antinuclear↗
PubMed1974

Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus.

Several types of antipolynucleotide antibodies were eluted by acid buffer or deoxyribonuclease treatment of glomeruli obtained from nine kidneys from patients with systemic lupus erythematosus (SLE). Anti-SDNA antibodies were found concentrated over serum levels in eight eluates, anti-NDNA in six eluates and anti-RNA Pr in four eluates; anti-DSRNA antibodies were not demonstrable in any eluate tested. Deoxyribonuclease treatment eluted a high incidence and greater quantity of anti-NDNA and anti-SDNA antibody, whereas anti-RNA Pr antibody was mainly eluted by acid buffer. Simultaneous studies of antibody and antigen in serial serum specimens and in glomeruli suggested that complexes of SDNA antibody or antigen excess were frequently deposited in SLE kidneys, in addition to complexes containing anti-NDNA and anti-RNA Pr. It was observed that studies of antibody titers alone were inadequate for predicting the types of complexes deposited in the kidney. Either antigen excess could obscure detection of humoral antibody or extremely high titers of antibody as observed for RNA Pr are not conducive to the formation of kidney localizing immune complexes in the absence of antigen. Immunofluorescence studies demonstrated the presence of SDNA antigen in most cases from which anti-SDNA antibody was eluted providing direct evidence for the presence of SDNA-anti-SDNA complexes in renal glomeruli. A study of complement components indicated that Clq was absent from cases in which little or no SDNA was deposited in renal glomeruli; although all nephritic kidneys demonstrated C3 deposits. Several hypotheses accounting for this observation are discussed, including the probable utilization of the alternate pathway by certain types of complexes and a direct reaction between C1q and circulating or tissue-bound NDNA or SDNA.

Animals↗
PubMed1973

Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity.

Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-gamma-globulins, partial cross-idiotypic specificity was demonstrated with other IgM anti-gamma-globulins. Such antisera classified these proteins into at least three groups. The major group which included 60% of the anti-gamma-globulins was particularly homogeneous. The anti-gamma-globulin specific antigens were detected best in hemagglutination and hemagglutination inhibition systems. They were not found in monoclonal IgM proteins that lacked anti-gamma-globulin activity although related antigens were detected at low concentrations in pooled immunoglobulin preparations as well as in heterogeneous anti-Rh antibodies. Several lines of evidence were obtained indicating that the antibody combining site was involved in the specific determinants. Attempts were made to analyze the fine specificity of each anti-gamma-globulin for the Fc fragment of different subclasses of human immunoglobulins as well as those of other species. Differences were observed but these were not readily related to the cross-specificity antigens. The anti-gamma-globulin specific antigens were very analogous to those previously described for monoclonal IgM cold agglutinins. Although each protein could be distinguished from all the others on the basis of individual idiotypic antigens, the antigens common to the specific groups of proteins with each of these activities were prominent and readily detected with multiple antisera. The results indicate basic similarities between proteins of a given activity even in unrelated individuals.

Agglutinins↗
PubMed1973

The occurrence of single-stranded DNA in the serum of patients with systemic lupus erythematosus and other diseases.

Single-stranded DNA (SDNA) occurs in high incidence and in greatest concentration in the sera of patients with systemic lupus erythematosus (SLE), where levels as high as 250 mug/ml were observed. SDNA appears to be an imunogen for anti-SDNA antibodies and forms complexes in vivo of both anti-SDNA-SDNA and anti-NDNA-SDNA types, which apparently play a role in the pathogenesis of the glomerulonephritis found in patients with SLE, SDNA is also found in high incidence but at lower levels in the sera of patients with rheumatoid arthritis. Lesser amounts of SDNA are found in several other diseases in which a low incidence of anti-SDNA antibodies is observed.

Adenosine↗
PubMed1971

Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease.

The specificities of anti-polynucleotide antibodies found in human sera were studied using several immunological procedures. Anti-native DNA (NDNA) antibodies and certain anti-double-stranded RNA (DSRNA) antibodies were found to react with single-stranded DNA (SDNA), and anti-NDNA antibodies were observed to react more avidly with SDNA than with NDNA in most sera tested. Antibodies to NDNA showed no preferential reactivity with NDNA or SDNA derived from mammalian tissue, bacterial, or viral sources. Precipitating antibodies reactive with individual bases, with common determinants of bases, and with common determinants of SDNA and NDNA were detected utilizing synthetic polydeoxyribonucleotides. Antibodies to DSRNA were also heterogeneous and reactive with both Poly A . Poly U and Poly I . Poly C in addition to reactivity with Poly A and SDNA. In contrast, antibodies to a ribonucleo-protein determined by hemagglutination and by precipitation showed no reaction with NDNA, SDNA, or DSRNA. Serial studies of serum specimens from patients with systemic lupus erythematosus (SLE) indicated that anti-NDNA antibodies were closely associated with disease activity. Titers of antibodies to SDNA or DSRNA were also frequently increased during these periods but in addition showed peaks during quiescent periods. Anti-NDNA antibodies were detected in most patients' sera at sometime during the course of the disease. Three patients were observed with active SLE, who did not develop anti-NDNA antibodies, even in the presence of severe renal disease. Evidence that other antigen-antibody systems may also play a role in the pathogenesis of the renal disease was particularly apparent in these patients. Anti-ribonucleoprotein antibodies were not well correlated with the peaks of antibody activity of other polynucleotide antibodies, suggesting that an independent immunogen was responsible for induction of these antibodies. The close association of certain populations of anti-polynucleotide antibodies during the course of active SLE, the presence of cross-reacting antigenic determinants of SDNA, NDNA, and DSRNA, the preferential avidity of anti-NDNA antibodies for SDNA, and the frequent increase of anti-SDNA antibodies in SLE and other diseases associated with active tissue destruction suggest that SDNA is a ubiquitous antigen that may stimulate the formation of antibodies reactive with a variety of polynucleotides.

Animals↗
PubMed1969

Antibodies to polynucleotides: distribution in human serums.

Hemagglutination procedures were used to determine the distribution of antibodies to native DNA, single-stranded DNA, and double-stranded RNA. Antibodies to all three polynucleotides were found in a high percentage of the serums of patients with systemic lupus erythematosus. Antibodies to native DNA occurred almost exclusively in serums of patients in the active stages of systemic lupus erythematosus, whereas antibodies to single-stranded DNA were observed in the serums of patients with several diseases and of some normal individuals.

Antibody Formation↗