scholarly journals ANTIBODIES TO POLYNUCLEOTIDES IN HUMAN SERA: ANTIGENIC SPECIFICITY AND RELATION TO DISEASE

1971 ◽  
Vol 134 (1) ◽  
pp. 294-312 ◽  
Author(s):  
D. Koffler ◽  
R. Carr ◽  
V. Agnello ◽  
R. Thoburn ◽  
H. G. Kunkel
Keyword(s):  
Renal Disease ◽  
Lupus Erythematosus ◽  
Close Association ◽  
Antigenic Specificity ◽  
Antigenic Determinants ◽  
Antibody Activity ◽  
Tissue Destruction ◽  
Severe Renal Disease ◽  
Human Sera ◽  
Antigen Antibody

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.

scholarly journals Antibodies in human sera to oncorna virus-like proteins from normal or leukemia marrow cell cultures.

1976 ◽  
Vol 144 (5) ◽  
pp. 1243-1253 ◽  
Author(s):  
S Louie ◽  
J E Curtis ◽  
J E Till ◽  
E A McCulloch
Keyword(s):  
Lupus Erythematosus ◽  
Competitive Inhibition ◽  
Marrow Cell ◽  
Leukemia Virus ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cross Reactivity ◽  
Antibody Activity ◽  
Human Sera ◽  
Blood Specimens ◽  
Radioimmunoprecipitation Assay

Some human marrows in culture release particles with oncornavirus-like properties. This study was designed to examine the immunological properties of similar particles in human marrow culture supernates. Leukemic and nonleukemic marrows were cultured for 5-7 days in the presence of [14C]uridine and [3H]leucine or [3H]glucosamine. Labeled supernatant components banding in sucrose gradient densities of 1.20-1.24 g/ml were used as antigen in a double antibody immunoprecipitation assay. The assay was validated by end point titrations and competition with unlabeled antigen; purified myeloma proteins were used as negative controls. Cross-reactivity with mammalian oncornaviruses, as judged by competitive inhibition of precipitation by these viruses, was slight and at the border of the sensitivity of the method. Precipitated antigens analyzed by SDS polyacrylamide gel electrophoresis contained three distinct polypeptides of about 70,000, 45,000 and 30,000 mol wt; these comigrated with the gp 70, pg 45, and p 30 of a murine leukemia virus. Similar polypeptides were obtained from both leukemic and nonleukemic marrow culture supernates. As determined by the radioimmunoprecipitation assay, 32 of 45 leukemic sera (71%), 36 of 45 normal sera (80%), 15 of 19 sera from family contacts of leukemic patients (79%), 14 of 21 cord blood specimens (67%), and 21 of 23 sera (91%) from patients with systemic lupus erythematosus had detectable antibody activity.

Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: a non-randomized prospective cohort study

Lupus ◽  
2012 ◽  
Vol 21 (9) ◽  
pp. 1025-1035 ◽  
Author(s):  
S Wang ◽  
X Li ◽  
L Qu ◽  
R Wang ◽  
Y Chen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Severe Adverse Effect ◽  
Open Label ◽  
Severe Renal Disease ◽  
Stage Renal Disease ◽  
End Stage

Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study — 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73m2). We compared the efficacy and adverse effects of TAC (0.04–0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m2 per month)/prednisone for six months followed by azathioprine (Aza) (100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P < 0.001), compared with the CYC group (4.9 ± 19.4 g/day), P = 0.001, and 65.0% (13/20) achieved partial remission at one month, compared with the CYC group (0/20), P < 0.001. The incidence of complete remission (CR) was significantly higher in the TAC group than in the CYC group (55.0% vs.15.0% by five months, P = 0.008, and 75.0% vs.40.0% by 12 months, P = 0.025, respectively). The significant improvement in serum anti-dsDNA and systemic lupus erythematosus (SLE) disease activity index (DAI) was in the TAC group relative to the CYC group at 12 months ( P = 0.031, P = 0.003, respectively). The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.

Localization of Intracellular Antigens in thin Sections with Ferritin Labeled Antibody

1970 ◽  
Vol 28 ◽  
pp. 174-175
Author(s):  
M.S. Shahrabadi ◽  
T. Yamamoto
Keyword(s):  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Antigenic Determinants ◽  
Conjugate Prior ◽  
Thin Sections ◽  
Specific Attachment ◽  
Intracellular Antigen ◽  
Antigen Antibody ◽  
Ideal Method ◽  
The Ideal

The technique of labeling of macromolecules with ferritin conjugated antibody has been successfully used for extracellular antigen by means of staining the specimen with conjugate prior to fixation and embedding. However, the ideal method to determine the location of intracellular antigen would be to do the antigen-antibody reaction in thin sections. This technique contains inherent problems such as the destruction of antigenic determinants during fixation or embedding and the non-specific attachment of conjugate to the embedding media. Certain embedding media such as polyampholytes (2) or cross-linked bovine serum albumin (3) have been introduced to overcome some of these problems.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

A longitudinal multiethnic study of biomarkers in systemic lupus erythematosus: Launching the GLADEL 2.0 Study Group

Lupus ◽  
2021 ◽  
pp. 096120332098858
Author(s):  
José A Gómez-Puerta ◽  
Guillermo J Pons-Estel ◽  
Rosana Quintana ◽  
Romina Nieto ◽  
Rosa M Serrano Morales ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Disease ◽  
Latin American ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Systemic Lupus ◽  
Original Cohort ◽  
Beneficial Effects ◽  
New Generation ◽  
Methodological Aspects

Introduction: After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. Methods: A new generation of “Lupus Investigators” in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. Results: So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. Conclusions: The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.

Immunochemical Studies on Antithrombin III

1979 ◽  
Author(s):  
E.J. McKay
Keyword(s):  
Antithrombin Iii ◽  
The Other ◽  
Antigenic Determinants ◽  
Immunochemical Analysis ◽  
Paradoxical Effect ◽  
Test Protocol ◽  
Agar Gel ◽  
High Affinity ◽  
Time Required ◽  
Antigen Antibody

Depressed Antithrombin III (AT) levels Increase thrombic tendency in man, therefore value in assaying this protein has been established. Immunochemical analysis of AT in clinical disease has however proved controversial, consequently systematic studies were undertaken to rationalize the requirements necessary to optimise these methods in particular electro-Immunoassay. The known binding affinity of AT for heparin has been exploited to differentiate high affinity AT from its inhibitor - protease complexes and has resulted in reports stating that heparin added to the agar gel prior to electrophoresis significantly reduces the time required for completion of antigen/antibody complexes. Our studies however have demonstrated that the antibody required for quantitative analysis must be capable of not only reacting with “native” antigenic determinants of AT but also with “neo” antigens that are exposed when inhibitor-protease complexes are formed. Heparin should not be used in the test protocol, for it has a paradoxical effect on Immunopreclpltation in gels, masking some antigenic determinants of unbound - high affinity AT on one hand, and appear to disrupt the Immunoprecipitin “rocket” formed with the inhibitor-protease complexes during electrophoresis on the other.

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