scholarly journals Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes.

1977 ◽  
Vol 145 (5) ◽  
pp. 1115-1130 ◽  
Author(s):  
S Izui ◽  
P H Lambert ◽  
G J Fournié ◽  
H Türler ◽  
P A Miescher
Keyword(s):  
Immune Complex ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Basement Membranes ◽  
Circulating Dna ◽  
Dna Complexes ◽  
Renal Glomeruli ◽  
Glomerular Deposits ◽  
Dna Antibodies ◽  
Similar Density

After injection of lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA,is 4--6S insize, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA) or DSDNA with some single-stranded regions. This purified DNA was shown to react with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. Based on these observations, the following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice is proposed. First, DNA, which has been released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM) through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. However, the possibility of direct deposition of immune complexes is not ruled out.

scholarly journals Clearance of circulating DNA-anti-DNA immune complexes in mice.

1982 ◽  
Vol 155 (4) ◽  
pp. 1210-1215 ◽  
Author(s):  
W Emlen ◽  
M Mannik
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Circulating Dna ◽  
Systemic Lupus ◽  
Free Antibody ◽  
Clearance Kinetics ◽  
Initial Clearance ◽  
Kinetics Of

DNA-anti-DNA immune complexes, produced from single-stranded DNA and IgG from a patient with systemic lupus erythematosus were cleared from the circulation of normal mice extremely rapidly, at a rate similar to the clearance of DNA alone. The initial clearance of these complexes was more rapid than the clearance of aggregated IgG, a surrogate immune complex containing a comparable number of IgG molecules, suggesting that the antigen (DNA) in the complexes significantly altered the clearance kinetics of the complexes. Analysis of the late clearance component of these complexes showed that anti-DNA is released back into the circulation after initial removal, and is then cleared at a rate similar to monomeric IgG. Whether this anti-DNA represents free antibody, or antibody bound to small nuclease digested DNA fragments, awaits further study.

SYSTEMIC LUPUS ERYTHEMATOSUS: PROTOTYPE OF IMMUNE COMPLEX NEPHRITIS IN MAN

1971 ◽  
Vol 134 (3) ◽  
pp. 169-179 ◽  
Author(s):  
D. Koffler ◽  
V. Agnello ◽  
R. Thoburn ◽  
H. G. Kunkel
Keyword(s):  
Immune Complex ◽  
Lupus Erythematosus ◽  
Dna Complexes ◽  
Immunofluorescence Studies ◽  
Serological Studies ◽  
Glomerular Deposits ◽  
Complex Deposition ◽  
Definition Of ◽  
Antigen Antibody ◽  
Insight Into

Serological studies, immunofluorescence studies, and immunochemical assays of glomerular eluates indicate that several antigen-antibody systems may be involved in the pathogenesis of the tissue lesions of SLE. The NDNA-anti-NDNA system appears to be operative in most patients with active SLE. In addition, antibodies to SDNA are found with considerable frequency in SLE sera and glomerular eluates. It is not known if these antibodies fix to NDNA which has been denatured after deposition in glomeruli or if SDNA-anti-DNA complexes are deposited initially. NDNA antigen has been demonstrated in both serum and glomerular deposits, and SDNA determinants have also been found in glomerular deposits. In addition, there is evidence that rheumatoid factor contributes to the immune complex deposition in certain patients either by fixing to preformed immune complexes or as part of an independent γ-globulin-anti-γ-globulin system. It is anticipated that the definition of these immune systems, and the assessment of their relative toxicity will provide insight into underlying etiologic factors as well as provide a sound basis for therapy in this form of glomerulonephritis.

Immune complexes: characteristics, clinical correlations, and interpretive approaches in the clinical laboratory.

1982 ◽  
Vol 28 (6) ◽  
pp. 1259-1271 ◽  
Author(s):  
S E Ritzmann ◽  
J C Daniels
Keyword(s):  
Immune Complex ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Complex Disease ◽  
Clinical Medicine ◽  
Clinical Laboratory ◽  
Therapeutic Monitoring ◽  
Serum Samples ◽  
Complement Components ◽  
Antigen Antibody

Abstract Immune-complex-mediated injury is thought to play a role in diseases such as rheumatoid arthritis, systemic lupus erythematosus, serum sickness, various infectious diseases, and malignancies. With increased appreciation of the biological and pathological significance of circulating immune complexes has come efforts to develop appropriate techniques for identifying and measuring them. Common approaches exploit such phenomena as the attachment of complement components to antigen-antibody complexes, the presence of specialized receptors for immune complexes at the surface of cells, and the ability of rheumatoid factor to bind with immune complexes. This variety of assay systems for immune complexes has yielded abstruse results in numerous human pathological conditions. Unfortunately, these results seldom correlate with one another in a given disease. Thus, use of a panel of immune complex assays has been recommended. Indirect consequences of immune complex disease may still be appraised and evaluated with some confidence in clinical medicine: measurements of C3 and C4, cryoglobulins, serum viscosity, and turbidity of serum samples. Measurement of immune complexes may be useful in diagnosis, prognosis, and therapeutic monitoring, but it is the characterization of immune complexes that holds the greatest potential for better understanding of disease mechanisms.

Circulating DNA-antibodies in systemic lupus erythematosus

1982 ◽  
Vol 2 (3) ◽  
pp. 103-106 ◽  
Author(s):  
T. Helve ◽  
A.-M. Teppo ◽  
P. Kurki ◽  
O. Wegelius
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Circulating Dna ◽  
Systemic Lupus ◽  
Dna Antibodies

scholarly journals Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Azita Sohrabian ◽  
Ioannis Parodis ◽  
Nellie Carlströmer-Berthén ◽  
Martina Frodlund ◽  
Andreas Jönsen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Activity Index ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Systemic Lupus ◽  
Double Stranded Dna

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.

scholarly journals Interaction between anti-DNA and anti-DNA-binding protein autoantibodies in cryoglobulins from sera of patients with systemic lupus erythematosus.

1986 ◽  
Vol 164 (4) ◽  
pp. 1029-1042 ◽  
Author(s):  
W H Reeves ◽  
N Chiorazzi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Binding ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Protein Complex ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Systemic Lupus ◽  
Variable Regions ◽  
Dna Antibodies

We have previously shown that sera from some patients with SLE and related disorders contain autoantibodies to a DNA-binding protein complex designated p70/p80. The present study shows that anti-p70/p80 autoantibodies are frequently accompanied by anti-DNA antibodies and cryoglobulins. When the cryoglobulins were isolated, they were found to be specifically enriched in both anti-p70/p80 and anti-DNA activities. The anti-p70/p80 and anti-DNA antibodies were found to be distinct populations of autoantibodies rather than a single crossreactive species, since they could be separated from one another by chromatography on DNA-cellulose. Certain human anti-DNA mAbs could inhibit the binding of autoimmune polyclonal anti-p70/p80 antibodies to p70/p80, suggesting that anti-DNA antibodies might also associate with the variable regions of some anti-p70/p80 antibodies in the cryoglobulins. Binding of one murine anti-p70/p80 mAb (111-12) also was inhibited by certain human anti-DNA mAbs, but the binding of another murine mAb (162-11) to a different epitope of p70/p80 was not. These studies suggest that certain anti-DNA antibodies may interact with the variable regions of a population of anti-p70/p80 antibodies. The cryoglobulins found in the sera containing both anti-p70/p80 and anti-DNA antibodies may represent immune complexes consisting, in part, of idiotype and antiidiotype.

scholarly journals Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake

2008 ◽  
Vol 205 (7) ◽  
pp. 1573-1582 ◽  
Author(s):  
Lisa C. Willcocks ◽  
Paul A. Lyons ◽  
Menna R. Clatworthy ◽  
James I. Robinson ◽  
Wanling Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Protein Expression ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Copy Number ◽  
Systemic Vasculitis ◽  
Normal Population ◽  
Human Neutrophils ◽  
Systemic Lupus

Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcγRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcγRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcγRIIIb. Reduced FcγRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody–associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.

scholarly journals In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus.

1976 ◽  
Vol 144 (2) ◽  
pp. 428-443 ◽  
Author(s):  
S Izui ◽  
P H Lambert ◽  
P A Miescher
Keyword(s):  
Lupus Erythematosus ◽  
Biological Significance ◽  
Basement Membranes ◽  
Basic Site ◽  
Binding Property ◽  
Local Formation ◽  
Dna Antibodies ◽  
Low Ionic Strength

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.

scholarly journals Polyamine-induced Z-DNA conformation in plasmids containing (dA-dC)n.(dG-dT)n inserts and increased binding of lupus autoantibodies to the Z-DNA form of plasmids

1994 ◽  
Vol 298 (2) ◽  
pp. 485-491 ◽  
Author(s):  
T J Thomas ◽  
T Thomas
Keyword(s):  
Complex Formation ◽  
Immune Complex ◽  
Dna Conformation ◽  
Circulating Dna ◽  
Inorganic Cations ◽  
Naturally Occurring ◽  
Dna Antibodies ◽  
Z Dna ◽  
Eukaryotic Genomes ◽  
Immune Complex Formation

Blocks of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences are ubiquitous in eukaryotic genomes. We examined whether naturally occurring polyamines, putrescine, spermidine and spermine, could provoke the Z-DNA conformation in plasmids pDHf2 and pDHf14 with 23 and 60 bp inserts respectively of (dA-dC)n.(dG-dT)n sequences using an e.l.i.s.a. Spermidine and spermine could provoke Z-DNA conformation in these plasmids, but putrescine was ineffective. For pDHf2 and pDHf14, the concentration of spermidine at the midpoint of B-DNA to Z-DNA transition was 25 microM, whereas that of spermine was 16 microM. Polyamine structural specificity was evident in the ability of spermidine homologues to induce Z-DNA. Inorganic cations, Co(NH3)6(3+) and Ru(NH3)6(3+), were ineffective. Our experiments also showed increased binding of anti-DNA autoantibodies from lupus patients as well as autoimmune MRL-lpr/lpr mice to pDHf2 and pDHf14 in the presence of polyamines. These data demonstrate that small blocks of (dA-dC)n.(dG-dT)n sequences could assume the Z-DNA conformation in the presence of natural polyamines. Increased concentrations of polyamines in the sera of lupus patients might facilitate immune complex-formation involving circulating DNA and anti-Z-DNA antibodies.

scholarly journals Selective suppression of retroviral gp70-anti-gp70 immune complex formation by prostaglandin E1 in murine systemic lupus erythematosus.

1980 ◽  
Vol 152 (6) ◽  
pp. 1645-1658 ◽  
Author(s):  
S Izui ◽  
V E Kelley ◽  
P J McConahey ◽  
F J Dixon
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Prostaglandin E1 ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus ◽  
Dna Antibodies ◽  
Total Concentrations ◽  
Immune Complex Formation

The effect of pharmacologic quantities of prostaglandin E1 (PGE) was investigated in three strains of mice (NZB X NZW, MRL/1, and BXSB) that spontaneously develop lupus-like glomerulonephritis. PGE-treatment prolonged survival and retarded the glomerular deposition of immune complex (IC) and the development of glomerulonephritis in NZB X NZW and MRL/1 mice, but did not similarly protect BXSB mice. Changes in the responsive strains correlated well with reduced amounts of circulating gp70 complexed with anti-gp70 antibodies compared with untreated controls, although total concentrations of gp70 (free and complexed) detectable in sera were similar in both groups of mice. The results strongly suggest that: (a) PGE selectively suppressed the immune response to retroviral gp70, (b) PGe had little effect on the quantity or quality of anti-DNA antibodies but did reduce the deposition of anti-DNA containing IC in the kidneys, and (c) gp70 IC appear to play an important role in the pathogenesis of glomerulonephritis in murine systemic lupus erythematosus.

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