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Biomedical subjects

W Emlen

Publications and source records attributed to W Emlen.

At least 19 recordsLinked to original sources
PubMed1999

Anti-beta2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome.

OBJECTIVE: Studies in rheumatologic and hematologic populations suggest that anti-beta(2)-glycoprotein I antibodies are more specific for the clinical manifestations of antiphospholipid syndrome than anticardiolipin antibodies. However, the association between anti-beta(2)-glycoprotein I and pregnancy loss remains uncertain. We sought to determine whether anti-beta(2)-glycoprotein I is associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 152 healthy fertile control subjects, (2) 141 subjects with unexplained recurrent spontaneous abortions, (3) 58 subjects with unexplained fetal deaths, and (4) 73 subjects with well-characterized antiphospholipid syndrome. Serum anticardiolipin and anti-beta(2)-glycoprotein I levels were determined by enzyme-linked immunoassay. RESULTS: Patients with antiphospholipid syndrome had significantly higher levels of immunoglobulin G and immunoglobulin M anticardiolipin and anti-beta(2)-glycoprotein I than the other 3 groups (P <.0001). However, women in the recurrent spontaneous abortion, fetal death, and fertile control groups had similar levels of each antibody. Similarly, there were no differences in the proportion of women with positive test results for each autoantibody in these 3 groups. Linear regression analysis showed significant correlation between anticardiolipin immunoglobulin G and beta(2)-glycoprotein I immunoglobulin G (R (2) = 0.544786, P =.0001) and anticardiolipin immunoglobulin M and beta(2)-glycoprotein I immunoglobulin M (R (2) = 0.525048, P =.0001). CONCLUSION: Both anticardiolipin and anti-beta(2)-glycoprotein I are associated with antiphospholipid syndrome. However, testing for anti-beta(2)-glycoprotein I does not identify additional patients with either recurrent spontaneous abortions or unexplained fetal deaths who initially have negative test responses for anticardiolipin. This is likely because of the strong correlation between the 2 autoantibodies. Our data do not support routine testing for anti-beta(2)-glycoprotein I in addition to testing for antiphospholipid antibodies in women with recurrent pregnancy loss and unexplained fetal death.

Abortion, Habitual↗
PubMed1999

Association of antibodies to beta2-glycoprotein 1 with pregnancy loss and pregnancy-induced hypertension: a prospective study in low-risk pregnancy.

OBJECTIVE: To determine whether higher levels of anti-beta2-glycoprotein 1 before 25 weeks' gestation are independently associated with either pregnancy loss or pregnancy-induced hypertension. METHODS: Serum samples for the immunoglobulin (Ig) G and IgM isotypes of anti-beta2-glycoprotein 1, anticardiolipin antibody, and antiphosphatidylserine were collected from 325 low-risk nulliparas who presented for prenatal care before 25 weeks' gestation. This cohort was followed prospectively for the development of pregnancy loss and pregnancy-induced hypertension. RESULTS: The adjusted odds ratios (OR) and 95% confidence intervals (CI) of elevated antiphospholipid antibody levels for pregnancy loss were: IgG anti-beta2-glycoprotein 1, OR 1.2 (CI 0.5, 2.8); IgG anticardiolipin antibody, OR 8.4 (CI 2.3, 31); and IgG antiphosphatidylserine, OR 5.2 (CI 1.4, 18.7). The relative risks of pregnancy loss for all IgG antiphospholipid antibodies were higher among women who had blood collected after 10 weeks' gestation compared with those studied before 10 weeks' gestation. However, there were only marginal differences in the attributable risks, suggesting that the impact of elevated levels of antiphospholipid antibodies might be similar in early and later stages of pregnancy. None of the antiphospholipid antibodies was associated with pregnancy-induced hypertension. CONCLUSION: In this study, elevated levels of IgG anticardiolipin and IgG antiphosphatidylserine antibodies were markers of pregnancy loss, but an elevated level of anti-beta2-glycoprotein was not a strong predictor of fetal loss.

Abortion, Spontaneous↗
PubMed1997

Clinical significance of antinuclear antibodies: comparison of detection with immunofluorescence and enzyme-linked immunosorbent assays.

OBJECTIVE: To compare the measurement of antinuclear antibodies (ANA) by immunofluorescence and by 6 different commercial enzyme-linked immunosorbent assays (ELISAs) in clearly defined patient groups and serum samples. METHODS: Serum samples were derived from 3 sources: 1) patients with a known clinical diagnosis of systemic lupus erythematosus (SLE) (group 1), 2) sera with known monospecific ANA reactivity (group 2), and 3) sera from consecutive patients for whom ANA testing had been ordered (group 3). Each of these sera was tested for the presence of ANA by immunofluorescence on HEp-2 cells, and by using each of 6 commercially available ELISA ANA kits. RESULTS: In patients with known clinical SLE, 88% were ANA positive by immunofluorescence. Positivity with the different ELISAs ranged from 62% to 90%. While most ELISAs successfully detected antibodies to SS-A, RNP, and Sm, there were significant differences between assays in the detection of anticentromere antibodies and anti-DNA. Measurement of ANA in consecutive patients for whom an ANA test was requested showed that, generally, those assays with high sensitivity for detection of SLE had a high false-positive rate, whereas those assays with a low false-positive rate failed to identify some patients with a clinical diagnosis of SLE. CONCLUSION: There are significant differences in the detection of ANA by immunofluorescence and different ELISA kits. Agreement between different assays is generally marginal. When ordering and interpreting an ANA test, the clinician must be familiar with the specific assay being used to measure ANA and the differences between the various ANA assays.

Antibodies, Antinuclear↗
PubMed1997

Antiphospholipid antibodies in healthy pregnant women.

This article discusses the prevalence and clinical significance of antiphospholipid antibodies (aPL) in the normal, healthy pregnant population. Although an increased risk for adverse fetal outcome has been shown in a small subset of this population, most pregnancies in aPL-positive mothers have successful outcomes. We review the variations in aPL levels during pregnancy and consider screening strategies and therapeutic interventions in healthy aPL-positive pregnant women.

Antibodies, Antiphospholipid↗
PubMed1996

Serum and urinary interleukin-6 in systemic lupus erythematosus.

Dysregulation of IL-6 production has been proposed as a pathogenic mechanism in SLE. We asked if serum or urine IL-6 levels could serve as indicators of systemic lupus erythematosus (SLE) disease activity. Using a sensitive enzyme-linked immunosorbent assay (ELISA), we measured serum and urine IL-6 in 56 SLE patients. Disease activity was assessed using a standard clinical index, the Systemic Lupus Activity Measure (SLAM). Only seven of 56 SLE patients had elevated serum IL-6 levels, compared with 1 of 32 controls (NS). SLE disease activity did not correlate with serum IL-6 levels. Sixteen of 50 SLE patients in whom urine IL-6 was measured exhibited elevated urine IL-6 levels, compared with 1 of 17 controls (p = < 0.05). Urine IL-6 levels correlated with overall disease activity and with the presence of active urinary sediment. Our results indicate that serum IL-6 is not a predictor of disease activity in SLE, but that urine IL-6 may be a marker of active nephritis.

Adult↗
PubMed1996

Measurement of serum hyaluronic acid in patients with rheumatoid arthritis: correlation with disease activity.

OBJECTIVE: To examine serum concentrations of hyaluronic acid (HA) in patients with rheumatoid arthritis (RA) and to investigate the relationship between clinical measures of disease activity and serum HA concentrations in these patients. METHODS: Sixty-five patients with established RA were enrolled and RA disease activity was measured by clinical variables. Serum samples obtained at the time of the clinical evaluation were assayed for serum HA, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP), and correlations between these laboratory variables and clinical disease activity were sought. RESULTS: Concentrations of serum HA were higher in patients with RA than in healthy controls. There was statistically significant correlation between patient age and serum HA and between serum HA and disease activity measured by physician assessment and number of swollen joints. Correction for age strengthened the correlation between serum HA and measures of disease activity. ESR did not correlate with any measure of clinical disease activity. CRP concentrations correlated with physician assessment of disease activity, and number of swollen joints and tender joints, but the correlation was not as strong as the correlation between serum HA and disease activity variables. CONCLUSION: Measurement of serum HA may be a useful measure of disease activity in patients with RA. Measurement of serum HA appears to be a better correlate of clinical disease activity in patients with RA than ESR or CRP.

Adult↗
PubMed1995

Antigen-based heteropolymers. A potential therapy for binding and clearing autoantibodies via erythrocyte CR1.

OBJECTIVE: To determine if complexes containing monoclonal antibodies to CR1 cross-linked with antigen (antigen-based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation. METHODS: AHP were constructed by cross-linking double-stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti-dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence-activated cell sorting. In addition, we used a monkey model to study in vivo the AHP-mediated clearance of passively infused human anti-dsDNA antibodies. RESULTS: Large amounts of lupus IgG anti-dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation. CONCLUSION: This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.

Animals↗
PubMed1995

Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests.

PURPOSE: To evaluate which serologic, cerebrospinal fluid (CSF), and neuroradiographic tests alone or in combination are most useful in the diagnosis of neuropsychiatric lupus erythematosus (NPLE). PATIENTS AND METHODS: Prospective study of patients with systemic lupus erythematosus (SLE) hospitalized with neuropsychiatric disease between January 1982 and December 1991. Special tests evaluated as part of this study included serum antinuclear antibodies, complement levels, serum and CSF antineuronal antibodies, CSF special protein studies (immunoglobulin G [IgG] index and oligoclonal bands), serum antiribosomal-P antibodies, serum antiphospholipid antibodies, and cranial magnetic resonance imaging (MRI). Diagnostic sensitivity, specificity, and positive predictive value (PPV) were determined for single tests and combinations of tests. RESULTS: Fifty-two NPLE patients were categorized by neuropsychiatric presentation (32 diffuse, 10 focal, and 10 complex presentations) and compared to 14 SLE control patients. Each NPLE patient with a diffuse or complex presentation had abnormal CSF IgG index/oligoclonal bands, elevated CSF antineuronal antibodies, and/or serum antiribosomal-P antibodies, yielding a sensitivity of 100%, specificity of 86%, and PPV of 95% for this combination of tests. Nine of 10 patients with focal presentations and all with complex disease had evidence of vasculitis/livedo reticularis, antiphospholipid antibodies, and/or a cranial MRI with multiple lesions, giving a sensitivity of 95%, specificity of 86%, and a PPV of 90% for this battery of tests. These combinations of tests correctly diagnosed all nine SLE patients whose initial diagnosis proved to be incorrect based on subsequent clinical course. Abnormal test results frequently normalized or improved with successful therapy. CONCLUSIONS: Specific tests for CSF antibodies are most useful diagnostically in diffuse NPLE, implicating autoantibodies in the pathogenesis of this NPLE presentation. In those patients with diffuse NPLE who present with primarily psychiatric disease, serum antiribosomal-P antibodies appear to be helpful. In contrast, focal NPLE appears to be mostly secondary to vascular occlusion, and the presence of dermal vasculitis/livedo reticularis, antiphospholipid antibodies, and/or an abnormal cranial MRI are most helpful diagnostically. Patients with complex presentations demonstrate abnormalities characteristic of both diffuse and focal NPLE. Abnormal tests can be followed serially and appear to correlate with clinical responses to therapy.

Adolescent↗
PubMed1995

Longitudinal measurement of anticardiolipin antibodies during normal pregnancy: a prospective study.

We have previously shown that elevation of anticardiolipin antibodies (aCL) at the first prenatal visit is associated with increased fetal loss in normal pregnancy. The variation in aCL levels during normal pregnancy has not been established. To examine this question we measured IgG, IgM and IgA aCL levels five times during pregnancy at weeks 5-15, 16-25, 26-35, 36-37 and at delivery. Data were analyzed to determine: (a) the within and between subject variability of aCL during pregnancy; (2) the temporal trend of aCL; and (3) the relation of serial measures of aCL with maternal complications of pregnancy. We divided our cohort of 354 subjects into two groups. Group A included those subjects with consistently normal levels of aCL and group B those subjects with at least one elevated level of aCL. In group A the within subject variability was relatively low (28-34%). In group B we found wide fluctuations in aCL levels and a within subject variability of 88-91%. Subjects in group B had no increase in maternal complications of pregnancy. The present data suggest that aCL may fluctuate significantly during normal pregnancy and there is little clinical value in measuring aCL on a serial basis during pregnancy.

Adolescent↗
PubMed1994

Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus.

SLE is a disease characterized by the generation of an immune response to intact nuclear Ags, especially components of the nucleosome, histones and DNA. The process of programmed cell death, or apoptosis, is characterized by cleavage of chromatin into oligonucleosomes and release of these nucleosomes into the extracellular space. To address the question of whether altered apoptosis might provide a source of extracellular nuclear Ags in SLE, we have examined apoptosis of lymphocytes isolated from patients with SLE, patients with rheumatoid arthritis (RA), and normal controls. Apoptosis was measured by three independent methods and confirmed by gel electrophoresis. Freshly isolated lymphocytes (t0) showed low levels of apoptosis. However, lymphocytes from SLE patients demonstrated a significant increase in the number of apoptotic cells at t0 compared with normal controls and RA patients. In tissue culture, lymphocytes from all patient groups underwent apoptosis, but the rate of apoptosis of lymphocytes derived from SLE patients was 2.35-fold faster than apoptosis of lymphocytes from normal controls or RA patients. The increased rate of apoptosis could not be accounted for by corticosteroid or cytotoxic medication. There was a significant correlation between SLE disease activity as measured by the systemic lupus activity measure and rate of apoptosis in vitro. The release of intact nucleosomes during apoptosis was measured by ELISA; lymphocytes from SLE patients released increased amounts of nucleosomal material into the extracellular space in direct proportion to the rate of apoptosis. Abnormal apoptosis of lymphocytes in SLE may provide a source of extracellular nuclear Ag to drive the immune response and to allow the formation of immune complexes. The demonstration of altered in vitro apoptosis of lymphocytes derived from SLE patients raises the possibility that abnormalities of apoptosis may contribute to the pathogenesis of SLE.

Adult↗
PubMed1994

Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.

OBJECTIVE: To determine if the presence of antiphospholipid antibody (aPL) in healthy pregnant women is associated with adverse pregnancy outcome, including 1) intrauterine fetal loss, 2) maternal pregnancy complications, 3) low birth weight, and 4) low 5-minute Apgar scores. DESIGN: Prospective cohort study in women with normal pregnancies. SETTING: Obstetrics clinic at the University of Colorado Health Sciences Center. PATIENTS: Eligible patients included 451 low-risk, nulliparous pregnant women who came to the obstetrics clinic before 25 weeks gestation; 408 were enrolled and 389 had blood drawn at the first prenatal visit and completed clinical follow-up. MEASUREMENTS: Blood for six aPL measures was drawn at the first prenatal visit and for 239 patients at delivery. RESULTS: Ninety-five patients (24.4%) had elevated aPL levels by one or more measures at the first prenatal visit: 15.8% of the aPL-positive and 6.5% of the aPL-negative patients experienced fetal loss (relative risk, 2.44; 95% CI, 1.29 to 4.62). However, an elevated IgG anticardiolipin antibody level at the first prenatal visit was the only aPL measurement that was significantly associated with fetal loss (relative risk, 3.5; CI, 1.56 to 8.07). Adjustment for confounding variables decreased the relative risk of aPL for fetal loss slightly, but the difference remained statistically significant. Neither a positive aPL result at the initial visit nor a positive result at delivery was associated with maternal complications of pregnancy, low birth weight, or low Apgar scores. CONCLUSIONS: Patients with elevated aPL levels at their initial prenatal visit had an increase in fetal loss but no increase in maternal pregnancy complications, low birth weight, or low Apgar scores. Immunoglobulin G anticardiolipin antibody was the only single test of aPL significantly associated with fetal loss.

Abortion, Spontaneous↗
PubMed1994

Treatment of hemorrhagic lupus pneumonitis with plasmapheresis.

Pulmonary hemorrhage is a rare and often fatal complication of systemic lupus erythematosus (SLE). Treatment with high-dose steroids and cyclophosphamide has been of only modest value, with a reported mortality of up to 92%. We have recently seen three patients with active SLE who developed acute life-threatening pulmonary hemorrhage. Diagnostic evaluation of these patients showed negative sputum and blood cultures, negative glomerular basement membrane antibodies, and negative antineutrophilic cytoplasmic antibodies. In two patients, an open-lung biopsy was performed, and histological examination showed granular alveolar immunofluorescence staining for immunoglobulin and complement components. Treatment with plasmapheresis was initiated with prompt resolution of symptoms and clearing of chest radiograph. Two patients had recurrent bleeds despite treatment with cyclophosphamide and high-dose steroids and required repeated intubation. Plasmapheresis resulted in rapid radiographic and clinical improvement on each occasion. Two patients survived long-term and are presently without pulmonary problems; one patient died of sepsis after initial response to plasmapheresis. The dramatic improvement of the pulmonary disease in these patients leads us to conclude that rapid initiation of plasmapheresis should be strongly considered in SLE patients with severe, life-threatening pulmonary hemorrhage.

Adult↗
PubMed1992

Regulation of nuclear antigen expression on the cell surface of human monocytes.

The expression of cell surface nuclear Ag was studied by examining the binding of anti-histone mAb to viable human peripheral blood cells. Freshly isolated cells showed no binding of these mAb. However, in vitro culture in the presence of LPS induced a dose-dependent expression of cell surface nuclear Ag on monocytes (M3+ cells). The addition of IL-1 beta to cultures also induced expression of cell surface nuclear Ag, whereas IFN-gamma was without effect. Release of nuclear material into the supernatants over time was demonstrated by using a chromatin-specific sandwich ELISA. Analysis of the DNA in the released nuclear material demonstrated banding at multiples of 190 bp, suggesting the release of polynucleosomes. Although LPS was required for cell surface nuclear Ag expression, it did not affect the release of nuclear material into the supernatants. The ability of monocytes to bind exogenous chromatin was studied by adding biotinylated-chromatin to PBL and detection with FITC-avidin. Freshly isolated PBL bound no chromatin, but when PBL were cultured in the presence of LPS, monocytes bound chromatin in a saturable manner. The LPS induction of the capacity to bind exogenous chromatin was blocked by cycloheximide. These data suggest that monocyte activation is associated with the expression of a chromatin (?nucleosome)-binding receptor and that this receptor is capable of binding nuclear material released into the cellular milieu. Monocytes may thus provide an important mechanism for the removal of extracellular nuclear material at sites of cell death and/or inflammation. The binding of nuclear Ag to cell surfaces and potential abnormalities of this binding may play a role in the induction of antinuclear antibodies and/or tissue damage in diseases such as SLE.

Antigens, Nuclear↗
PubMed1992

Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes.

Complement receptor 1 (CR1) on primate red blood cells (RBC) binds most complement-fixing immune complexes in the circulation. It has been postulated that by binding them, RBC keep immune complexes in the intravascular space and deliver them to the tissue macrophages of the mononuclear phagocyte system. We have developed an in vitro model to study the transfer of RBC-bound immune complexes (heat-aggregated IgG and DNA-anti-DNA) to phagocytic cells (human monocytes). Transfer of immune complexes from RBC to monocytes occurred significantly more rapidly than monocyte uptake of the same immune complexes from solution. In the transfer process, complex-bearing RBC were not bound or sequestered by the monocytes. To define the monocyte receptors involved in binding immune complexes from the RBC surface, monocyte receptors were blocked with MoAbs (anti-CR1, anti-FcRII) or EDTA (to block CR3). Monocyte binding of immune complexes primarily used CR1 with a small contribution from FcRII, and with little or no contribution from CR3 and FcRI. Uptake of immune complexes from solution employed the same monocyte receptors as binding of complexes from the RBC surface. Immune complexes in solution bound to RBC and to monocytes with equally high avidity (approximately 1 x 10(11) l/M), but monocytes expressed a 15-20-fold greater number of immune complex binding sites. We propose that immune complexes distribute between RBC and monocytes according to the binding capacity of these cells, such that at equal or high RBC/monocyte ratios as would be seen in the circulation immune complexes bind to RBC, but at low RBC/monocyte ratios (as would be seen in the sinusoidal circulation of the liver and spleen), most immune complexes bind to monocytes. To define the pathway by which immune complexes move from RBC to monocytes, their release from RBC CR1 was examined. Under various conditions, the dissociation rate was extremely slow, and did not increase with the addition of monocyte supernatants. To examine whether factor I-mediated processing of immune complexes enhances binding of immune complexes to monocytes, RBC-bound complexes were released with factor I, and binding of these 'processed' immune complexes to monocytes was examined. Monocyte binding of these processed immune complexes was slower than of control ones; furthermore, performance of transfer experiments at 4 degrees C, which significantly shows enzymatic processes, did not decrease the rate of immune complex transfer from RBC to monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1990

A new ELISA for the detection of double-stranded DNA antibodies.

The accurate detection of antibodies to double-stranded DNA is important in the diagnosis and management of patients with systemic lupus erythematosus (SLE). We have developed an ELISA in which plasmid dsDNA is biotinylated and bound to streptavidin coated wells. The biotinylated DNA did not lose is antigenicity, and the DNA which bound to the plate remained double-stranded. Only small amounts of DNA were required to coat the plates, and binding was highly reproducible. After defining the normal range of the assay, sera from patients with various conditions were examined; 0 out of 97 controls were positive, 0 out of 36 patients with RA were positive, 0 out of 14 patients with scleroderma, and two out of 18 patients with chronic liver disease were positive. In contrast, 52% of unselected SLE patients were positive, and there was a good correlation between level of DNA antibodies and disease activity. Comparison of this assay with other DNA assays (the Farr, Millipore, filter, and a commercial ELISA) showed a high degree of correlation between this ELISA and each of the other assays. Furthermore, screening of randomly selected ANA positive patients with this assay failed to show a high false positive rate as has been reported with other anti-DNA ELISAs. This assay is simple to perform, requires small amounts of DNA to coat the plate, is highly reproducible, and is specific for IgG antibodies to dsDNA.

Antibodies, Antinuclear↗
PubMed1989

Binding of model immune complexes to erythrocyte CR1 facilitates immune complex uptake by U937 cells.

The E C3b/C4b receptor (CR1) has been shown to rapidly bind large complement-fixing immune complexes (IC) both in vivo and in vitro. It has been proposed that E (RBC) CR1 act as a shuttle mechanism, binding circulating IC and transporting them to tissue macrophages, thereby preventing their deposition in target tissues. In this study we have established an in vitro model system with which to study the transfer of model IC from CR1 on the RBC surface to phagocytic cells. Aggregated IgG (AHG) was opsonized with C3b, bound to RBC CR1, and the binding of these RBC-bound IC by a human monocyte cell line (U937 cells) was examined. U937 binding of AHG from the RBC surface was complete within 2 min, whereas binding of the same AHG from solution required 30 to 60 min. Despite the difference in kinetics of binding, the total amount of IC bound by U937 cells at equilibrium was the same for RBC-bound AHG and for AHG in solution. The transfer of AHG from the RBC to the U937 cell did not require exogenous factor I and was not accompanied by binding of RBC to U937 cells or by erythrophagocytosis. Our data lend support to the hypothesis that binding of IC to RBC CR1 may facilitate the clearance of IC from the circulation by enhancing their uptake by phagocytic cells.

Antibodies, Anti-Idiotypic↗
PubMed1989

Binding of double-stranded DNA to glomeruli of rats in vivo.

In vivo binding of double-stranded DNA (dsDNA) to renal glomeruli of rats was examined. 125I-dsDNA (600 basepairs) was perfused with 131I-IgG as a blood marker into the right renal artery of normal rats, and blood flow was restored. After 10 minutes, isolated glomeruli showed a specific uptake of DNA, which increased in a saturable fashion with increasing doses of administered DNA. To exclude the possibility that 125I in the glomeruli represented only DNA breakdown products, we extracted the DNA from the glomeruli for analysis by polyacrylamide gel electrophoresis. The extracted DNA was 120-200 bp in size, which is large enough to bind antibodies to DNA. In contrast, the radioactivity of DNA taken up by the liver or renal tissues other than glomeruli was predominantly trichloroacetic acid soluble, i.e., less than 15 bp. Immunofluorescence studies showed that antibodies to DNA, administered after DNA, were present in glomeruli. Our data indicate that dsDNA binds to glomeruli in vivo in a saturable manner, and remains large enough to be antigenic. Therefore, the binding of DNA to glomeruli, followed by interaction with antibodies to dsDNA may be a mechanism for DNA-anti-DNA complex formation in glomeruli in patients with systemic lupus erythematosus.

Animals↗