Abstract
In order to determine whether circulating antigen-antibody complexes in systemic lupus erythematosus (SLE) consist of DNA and anti-DNA, cryoglobulins were isolated from the sera of 38 patients with SLE nephritis and analysed for DNA and anti-DNA. Cryoglobulins were detected in 36 of the 38 sera, and DNA was found in 30 of 33 examined by either fluorescence of ethidium bromide or a radioimmunoassay. Anti-DNA activity was not detectable in any of the whole cryoglobulins but anti-IgG activity was found in 17. Twenty cryoglobulins were therefore treated by acid dissociation and ultracentrifugation to obtain isolated immunoglobulins; IgG was isolated from all, and IgM from eight. Using a modified Farr assay to detect anti-dsDNA and an enzyme-linked immunoadsorption assay to detect anti-ssDNA, anti-dsDNA activity alone was found in five IgG fractions, anti-ssDNA activity alone in five, and both anti-ds- and anti-ssDNA activity in four. Anti-dsDNA activity was found in three of the IgM fractions. In all, anti-dsDNA activity was found in nine of these 20 cryoglobulins, and anti-DNA in 14. Analysis of these 14 cryoglobulins with anti-DNA Ig fractions showed that there was enrichment of the IgG anti-DNA activity in the cryoglobulin compared to the patient's serum in all but two cases. In six of the 20 cryoglobulins studied there was no detectable anti-DNA activity in isolated IgG or IgM fractions. We therefore concluded that DNA-anti-DNA complexes were present in most of our patients with SLE nephritis, but there was clearly a substantial minority in whom they were undetectable. In some of the latter who also had active disease the cryoglobulins had anti-IgG activity. Thus it would seem that SLE can occur in the absence of DNA-anti-DNA complexes, but with other complexes present. DNA was also found in cryoglobulins isolated from patients with idiopathic glomerulonephritis, but, in contrast to recent reports, anti-DNA activity was not detectable in immunoglobulins isolated from their cryoglobulins.
MeSH Terms
Adult
Antibodies, Antinuclear/analysis
Antigen-Antibody Complex/analysis
Cryoglobulins/analysis
DNA/immunology
Glomerulonephritis/etiology,immunology
Humans
Immunoglobulin G/immunology
Lupus Erythematosus, Systemic/complications,immunology
Chemicals
Antibodies, Antinuclear
Antigen-Antibody Complex
Cryoglobulins
Immunoglobulin G
DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Adu D
Dobson J
Williams D G
References (28)
28 references, click to expand
-
A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization.
J Mol Biol. 1967 Jul 14;27(1):87-106
PMID: 6033613
-
Immunological studies concerning the nephritis of systemic lupus erythematosus.
J Exp Med. 1967 Oct 1;126(4):607-24
PMID: 4168098
-
Deoxyribonucleic acid antibody: a method to detect its primary interaction with deoxyribonucleic acid.
Science. 1968 Aug 23;161(3843):806-7
PMID: 4969617
-
Character of anti-DNA antibodies in systemic lupus erythematosus.
Clin Exp Immunol. 1971 Apr;8(4):551-61
PMID: 4102680
-
Anti-DNA activity in systemic lupus erythematosus. A diagnostic and therapeutic guide.
Ann Rheum Dis. 1971 May;30(3):259-64
PMID: 4996903
-
Measurement of DNA in isolated granulocytes by the ethidium technique.
Anal Biochem. 1973 Jan;51(1):1-10
PMID: 4734574
-
DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera.
J Clin Invest. 1973 Apr;52(4):789-95
PMID: 4693646
-
Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q.
J Clin Invest. 1974 Aug;54(2):297-309
PMID: 4847246
-
Native and denatured DNA, cross-linked and palindromic DNA and circular covalently-closed DNA analysed by a sensitive fluorometric procedure.
Biochem Biophys Res Commun. 1974 Nov 27;61(2):396-403
PMID: 4477007
-
Specific concentration of polynucleotide immune complexes in the cryoprecipitates of patients with systemic lupus erythematosus.
J Clin Invest. 1975 Sep;56(3):563-70
PMID: 1080489
-
The Raji cell radioimmune assay for detecting immune complexes in human sera.
J Clin Invest. 1976 Jan;57(1):169-82
PMID: 128562
-
Human anti-DNA antibody: reference standards for diagnosis and management of systemic lupus erythematosus.
Ann Rheum Dis. 1975 Oct;34(5):438-43
PMID: 1221924
-
Immunology of DNA. IV. Quantitative aspects of the Farr assay.
J Immunol Methods. 1976;11(2):153-63
PMID: 932447
-
Disease activity in the nephritis of systemic lupus erythematosus in relation to serum complement concentrations. DNA-binding capacity and precipitating anti-DNA antibody.
Clin Exp Immunol. 1976 Sep;25(3):418-27
PMID: 1085678
-
Cryoglobulinaemia in Henoch-Schönlein purpura.
Br Med J. 1977 Jul 16;2(6080):163-5
PMID: 871825
-
Direct evidence for circulating DNA/anti-DNA complexes in systemic lupus erythematosus.
Arthritis Rheum. 1978 Jan-Feb;21(1):17-22
PMID: 623690
-
Failure to detect circulating DNA--anti-DNA complexes by four radioimmunological methods in patients with systemic lupus erythematosus.
Clin Exp Immunol. 1977 Dec;30(3):384-92
PMID: 606451
-
A solid phase enzyme-linked immunosurbent assay (ELISA) for the demonstration of antibodies against denatured, single-stranded DNA in patient sera.
Scand J Immunol. 1978;7(2):151-7
PMID: 349676
-
Systemic lupus erythematosus with negative LE cells and antinuclear factor.
J Rheumatol. 1978 Summer;5(2):142-7
PMID: 78982
-
Value of immune-complex assays in diagnosis and management.
Lancet. 1978 Aug 12;2(8085):359-64
PMID: 79721
-
Identification of antinative DNA antibodies in cryoglobulinemic states.
Am J Med. 1978 Sep;65(3):437-45
PMID: 362916
-
Circulating DNA:anti-DNA complexes in systemic lupus erythematosus. Detection and characterization by ultracentrifugation.
J Clin Invest. 1979 Jul;64(1):191-8
PMID: 36410
-
Systemic lupus with nephritis: a long-term study.
Q J Med. 1979 Jan;48(189):1-24
PMID: 482585
-
Immune complex detection in glomerular diseases.
Nephron. 1979;24(3):105-13
PMID: 386153
-
Lymphocytotoxic antibodies in laboratory personnel exposed to SLE sera.
Lancet. 1979 Nov 24;2(8152):1141-2
PMID: 91880
-
Immunochemical demonstration of cryoprecipitable anti-native DNA antibody and DNA in the serum of patients with glomerulonephritis.
J Immunol. 1980 Jan;124(1):127-33
PMID: 6985635
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
A modification of the latex-fixation test for the study of rheumatoid arthritis.
J Lab Clin Med. 1957 Jul;50(1):113-8
PMID: 13439272