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J Rauch

Publications and source records attributed to J Rauch.

At least 73 records · Page 4Linked to original sources
PubMed1990

Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus.

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.

Adolescent↗
PubMed1989

Distinguishing plasma lupus anticoagulants from anti-factor antibodies using hexagonal (II) phase phospholipids.

The association of lupus anticoagulant antibodies with thrombosis, thrombocytopenia, and multiple spontaneous abortions underlines the importance of diagnostic assays which are able to distinguish these antibodies from anti-factor antibodies and factor deficiencies, as all three prolong in vitro coagulation assays measuring activated partial thromboplastin time (APTT). Heparin also prolongs the APTT assay and often interferes with the detection of lupus anticoagulant activity. The present study describes a direct and simple dilute APTT assay in which plasma is preincubated with hexagonal (II) phase phosphatidyl ethanolamine (PE). Using this system, the lupus anticoagulant antibody activity of 10 randomly selected plasmas from SLE patients was inhibited by 81.2-99.5%, while prolongation of the APTT assay by 6 different anti-factor antibody-containing plasmas, 5 factor deficient plasmas, and 6 heparin-containing plasmas remained unaffected. Inhibition was dependent on epitopes exposed when PE was presented in the hexagonal (II) phase. This data suggests that hexagonal (II) PE is specifically recognized by lupus anticoagulant antibodies in SLE patients and may play a role in the etiology of the disease.

Autoantibodies↗
PubMed1988

Relative sensitivity of different tests in the detection of low titer lupus anticoagulants.

Lupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

Blood Coagulation Factors↗
PubMed1988

Hybridoma lupus autoantibodies can bind major cytoskeletal filaments in the absence of DNA-binding activity.

A panel of 65 systemic lupus erythematosus (SLE) and 61 normal-derived human hybridoma auto-antibodies was studied for cytoskeletal reactivity, using an indirect immunofluorescence method. Reactivity with the cytoskeleton was expressed 3 times more frequently in the SLE-derived antibody group and included intermediate filaments, microfilaments, microtubules, and centrioles. By immunoblot analysis, the antigenic specificity of intermediate filament-reactive SLE hybridoma antibodies was not restricted to vimentin, but included cytokeratins and desmin. The antibodies were also studied for their DNA-binding, lupus anticoagulant, and rheumatoid factor activities. These autoantibody activities were expressed 3-5 times more frequently in the SLE-derived group. The ability to bind DNA was not a prerequisite for reactivity with intermediate filament proteins. Our findings suggest that there are at least 2 subsets of cytoskeletal-reactive hybridoma antibodies: those that recognize epitopes found only on cytoskeletal proteins, and those that recognize epitopes common to both DNA and certain cytoskeletal proteins. In addition, we hypothesize that there may be a third subset of antibodies that recognize a phosphate-containing moiety (phospholipid or phosphoprotein) associated with cytoskeletal filaments.

Adult↗
PubMed1988

Autoimmune diseases other than lupus share common anti-DNA idiotypes.

We examined the sera of 170 patients with various autoimmune diseases other than systemic lupus erythematosus (SLE) for the presence of an anti-DNA antibody idiotype termed 16/6 and known to occur with high frequency in sera of patients with SLE. The idiotype was found in 6/15 sera from patients with polymyositis (49%), 3/18 with multiple sclerosis (17%), 3/18 with primary Sjögren's syndrome (18%), 9/40 with autoimmune thyroid diseases (23%), 2/35 with myasthenia gravis (6%), and 3/42 patients with rheumatoid arthritis (7%). The idiotype was not detected among 12 patients with scleroderma or 77 normal controls. The presence of the 16/6 idiotype was associated with the presence of another anti-DNA idiotype termed 134-Id. Serum samples were also tested for activity against DNA, various synthetic polynucleotides, and cardiolipin. The serum activity against these antigens was found to be polyspecific, though overlap in reaction against the various polynucleotides was not absolute. The 16/6 idiotype is thought to be coded by a germline gene. The presence of this idiotype in various autoimmune diseases points to a pathophysiologic link between the diseases.

Autoantibodies↗
PubMed1988

Expression of an interspecies idiotype in sera of SLE patients and their first-degree relatives.

Sera from 29 SLE patients and 81 first-degree healthy family members were tested for quantitative expression of a cross-reactive idiotype present on a murine monoclonal anti-Sm autoantibody (Y2). Forty-one percent of SLE patients and 27% of all relatives showed increased serum levels of the Y2 idiotype compared to 6% in a normal, unrelated control group. In addition, female relatives of SLE patients showed slightly increased levels of anti-Sm antibodies compared to male relatives (15% vs 3%). In one of the 28 families and three unrelated SLE patients studied, there was a significant correlation between the Y2 idiotype expression and expression of another idiotype present on anti-DNA antibodies (1341d). Affinity column absorption studies showed that these two idiotypes were present on different antibody molecules. This study demonstrates: (1) a genetic predisposition for an anti-Sm antibody idiotype expression in humans; and (2) that two different idiotypes may be under parallel or coordinate regulation.

Antibodies, Antinuclear↗
PubMed1988

Antiphospholipid antibodies in systemic lupus erythematosus: evidence of an association with positive Coombs' and hypocomplementemia.

Anticardiolipin antibodies (aCL) were evaluated in 65 consecutive patients with systemic lupus erythematosus using an enzyme linked immunoassay (ELISA) and were detected in 14 (22%). There was no association of aCL with active disease, specific clinical manifestations, high DNA binding or circulating immune complex levels. The presence of aCL was associated with lupus anticoagulant activity (p less than 0.001), positive VDRL (p less than 0.05), and lower mean platelet counts (p less than 0.05) and C3 levels (p less than 0.05). Both aCL and lupus anticoagulant activity were associated with positive Coombs' (p less than 0.01) and low C4 (p less than 0.01 and p less than 0.05, respectively). Analysis of red blood cell (RBC) eluates and absorption studies using fixed RBC suggested that some aCL may act as anti-RBC antibodies, likely directed at membrane phospholipid epitopes. Furthermore, we hypothesize that complement may participate as a cofactor maximizing lupus anticoagulant activity.

Adult↗
PubMed1987

Lupus anticoagulant and antiplatelet properties of human hybridoma autoantibodies.

The clinical association of lupus anticoagulant antibodies with thrombocytopenia and thrombosis was the rationale for investigating the in vitro reactivity of these human hybridoma lupus anticoagulant antibodies with platelets. Fifty human hybridoma antibodies from 13 patients with systemic lupus erythematosus, 2 women with multiple spontaneous abortions, and 4 normal individuals were analyzed for lupus anticoagulant, antiplatelet, anti-DNA, and antiphospholipid reactivities. Of the hybridoma antibodies studied, 25 had lupus anticoagulant activity, 21 had antiplatelet reactivity, and 7 of these antibodies had both lupus anticoagulant and antiplatelet properties. No correlation was found between lupus anticoagulant antibody activity and antiplatelet, anti-denatured DNA, anticardiolipin, anti-egg phosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidylcholine reactions. In contrast, antiplatelet activity was strongly correlated with antiphosphatidylethanolamine (rho = 0.761, p less than 0.001), anticardiolipin (rho = 0.748, p less than 0.001), and anti-dDNA (rho = 0.745, p less than 0.001) reactivities. Pretreatment of platelets with deoxyribonuclease, ribonuclease, trypsin, or phospholipases A2 and C resulted in different effects on the binding of individual hybridoma antibodies to platelets, suggesting that antiplatelet antibodies may recognize different epitopes on the platelet membrane. Our data demonstrate that most hybridoma lupus anticoagulant antibodies did not bind directly to platelets in vitro. This suggests that additional serum factors may be required in vivo to explain the association of these antibodies with thrombocytopenia and thrombosis.

Antibody Specificity↗
PubMed1987

Common lupus anti-DNA antibody idiotypes in chronic liver diseases.

Chronic liver diseases may be associated with the appearance of antinuclear antibodies. To further analyze the relationship between connective tissue and liver diseases the sera of 88 patients with chronic liver disorders were examined for the presence of common lupus anti-DNA idiotypes (16/6-id, 134-id, and 32/15-id), using an enzyme-linked immunosorbent assay. The 16/6-id was found in 58 (65.9%), the 134-id in 43 (48.9%), and the 32/15-id in 13 (14.8%) of the patients' sera. Distinct diagnostic groups displayed different lupus anti-DNA idiotype profiles. Patients with primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH) had mainly the 16/6 idiotype, while in alcoholic (AC) and in cryptogenic cirrhosis (CC) the 16/6-id and 134-id were the main idiotypes recorded. There was considerable correlation among the different anti-DNA idiotypes but not between any of these idiotypes and an unrelated common anti-HBsAg idiotype. The occurrence of the various idiotypes was not found to be correlated with increased serum immunoglobulin levels. It can be concluded that the similarities between chronic liver diseases and connective tissue diseases are extended also to the presence of specific common anti-DNA antibody idiotypes.

Autoantibodies↗
PubMed1987

Polyfunctional properties of hybridoma lupus anticoagulant antibodies.

Lupus anticoagulant antibodies are antiphospholipid antibodies which are characterized by their ability to prolong the clotting time in in vitro coagulation assays measuring the partial thromboplastin time (PTT). In our study, we have analyzed 11 hybridoma lupus anticoagulant antibodies and studied their reactivity with hexagonal and lamellar phospholipids, DNA, IgG, cytoskeletal components, and intact platelets. Our results demonstrate that hexagonal phase phospholipids but not lamellar phospholipids were able to neutralize the lupus anticoagulant activity of all 11 hybridoma antibodies. However, the lupus anticoagulant antibodies differed from one another in their reactivity with DNA, the Fc fragment of IgG, cytoskeletal proteins and platelets. Some of the lupus anticoagulant antibodies reacted with all of these structures, while others reacted with only some or none of the antigens tested. Isoelectric focusing gel analysis confirmed that this polyreactivity was due to a single antibody. Direct binding of lupus anticoagulant antibodies to intact platelets was shown to correlate with the DNA binding activity of the antibodies. Lupus anticoagulant antibodies were also capable of inducing a morphological shape change in platelets. Our data suggest that hybridoma lupus anticoagulant antibodies may react as lupus anticoagulant antibodies only, anti-DNA antibodies, rheumatoid factors, anticytoskeletal antibodies, and antiplatelet antibodies. The degree of overlap in these subgroups and the epitopes responsible for these multiple reactivities remain to be determined.

Antibodies, Antinuclear↗
PubMed1986

Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems.

Antibodies to phospholipids may have important physiological and biological functions. Lupus anticoagulants represent a subclass of anti-phospholipid antibodies which are characterized by their ability to prolong the clotting time in in vitro coagulation assays measuring partial thromboplastin time (PTT) (Thiagarajan, P., Shapiro, S. S., and DeMarco, L. (1980) J. Clin. Invest. 66, 397-405). In the present study, we produced hybridomas by fusing lymphocytes from 13 systemic lupus erythematosus patients with the GM 4672 lymphoblastoid line. Of the resulting 67 hybridoma autoantibodies, 14 (21%) were found to prolong a modified PTT assay, and 11 of these antibodies were analyzed further. Competition experiments, using a modified PTT assay, demonstrated that hexagonal phase phospholipids, including natural and synthetic forms of phosphatidylethanolamine, were able to neutralize the lupus anticoagulant activity of all 11 hybridoma antibodies. In contrast, lamellar phospholipids, such as phosphatidylcholine and synthetic lamellar forms of phosphatidylethanolamine, had no effect on the anticoagulant activity. Thus, these antibodies are capable of recognizing phospholipids on purely structural criteria. The demonstration that anti-phospholipid antibodies are able to distinguish between different structural arrangements of phospholipid may have important implications regarding the immunoregulation of autoimmunity.

Antibodies↗
PubMed1986

A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members.

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE.

Adolescent↗
PubMed1986

Human-human hybridoma autoantibodies with both anti-DNA and rheumatoid factor activities.

Human hybridomas have been produced by fusing peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with the GM 4672 human cell line. 262 hybridoma clones from the fusions of four RA and five SLE patients were screened for binding to denatured DNA (dDNA), native DNA, and the Fc fragment of human IgG (HIgG). Of the 17 hybridoma antibodies (nine RA, eight SLE) selected for strong binding to denatured DNA, Fc, or both, five reacted with dDNA only, one with Fc only, and eight with both dDNA and Fc. Hybridoma supernatants exhibiting dual reactivity were absorbed over HIgG and bovine serum albumin (BSA)-Sepharose immunoabsorbent columns. The reactivities to both DNA and HIgG were completely removed by the HIgG column but unaffected by passage over the BSA column, and both DNA binding and rheumatoid factor activities were recovered in the acid eluates from the Sepharose-IgG column. The binding of dual reactive hybridoma autoantibodies to the Fc fragment of HIgG was specifically competed by dDNA and HIgG, providing additional evidence that one antibody may be capable of reacting both as a rheumatoid factor and as an anti-DNA antibody.

Antibodies, Antinuclear↗
PubMed1986

Monoclonal anti-tuberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis.

Classical models of experimental autoimmune diseases, such as adjuvant arthritis entail the use of mycobacteria. Furthermore, BCG immunotherapy may be followed by arthritic symptoms. To test the infection-autoimmunity relationship of mycobacteria, we used monoclonal antibodies raised against M. tuberculosis and against DNA. Murine monoclonal anti-TB antibodies were found to react with ssDNA, dsDNA and other polynucleotides. Monoclonal anti-DNA autoantibodies derived from patients and mice with SLE bound to three glycolipids shared among all mycobacteria and derived from mycobacterial cell wall. Prior incubation of the antibodies with ssDNA and other polynucleotides or with glycolipid antigens inhibited binding. These results indicate that infecting mycobacteria share antigens with human tissue, thus accounting in part for the production of autoantibodies in mycobacterial infections.

Animals↗
PubMed1985

Detection of cross reactive anti-DNA antibody idiotypes on tissue-bound immunoglobulins from skin biopsies of lupus patients.

Cross-reactive anti-DNA antibody idiotypes have been identified on tissue-bound immunoglobulins from skin biopsies of patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE). Four polyclonal and two monoclonal anti-idiotypic reagents were used to screen biopsies from 24 patients with SLE, 23 patients with DLE, and 15 other patients with IgM-positive skin biopsies. Up to 46% of the SLE patients and 30% of the DLE patients were found to share idiotypes present on immunoglobulins deposited at the dermal-epidermal junction. Inhibition studies in four patients indicated that the idiotypes were on anti-DNA antibodies. In contrast, none of the anti-idiotypic antibodies bound to any of the control biopsies. These findings imply that some tissue-bound autoantibodies are derived from related families of high-frequency germ-line genes that are expressed in both SLE and DLE.

Antibodies, Antinuclear↗
PubMed1985

Specific and shared idiotypes found on hybridoma anti-DNA autoantibodies derived from rheumatoid arthritis and systemic lupus erythematosus patients.

The idiotype determinants found on hybridoma anti-DNA autoantibodies produced from the fusion of peripheral blood lymphocytes from 13 systemic lupus erythematosus (SLE) and five rheumatoid arthritis (RA) patients with the GM 4672 human lymphoblastoid line were analyzed. A total of 47 SLE and 21 RA hybridomas were studied, of which 26 SLE and 10 RA produced anti-DNA autoantibodies. Rabbit antisera, raised to six of the SLE hybridoma anti-DNA IgM antibodies, were rendered idiotype specific by multiple absorptions on human IgM and IgG immunoabsorbent columns. In direct binding radioimmunoassays, all six anti-idiotype antisera reacted specifically with the anti-DNA antibody used as immunogen. In competition studies, five anti-idiotype antisera were able to inhibit the binding of their homologous idiotype to DNA-coated tubes. In addition, DNA and polynucleotides inhibited the binding of the five idiotypes to anti-idiotype-coated tubes, suggesting that these anti-idiotypes react with idiotype determinants located within the antigen-combining sites of the anti-DNA antibody molecules. Shared idiotypes were detected among the 68 hybridoma antibodies by direct binding studies on anti-idiotype-coated tubes. Our results revealed that 58% (21/36) of the anti-DNA antibodies and 16% (5/32) of the non-DNA-binding antibodies reacted with at least one anti-idiotype serum. Five anti-idiotype antisera reacted only with hybridoma anti-DNA antibodies from SLE patients. The other anti-idiotype antiserum reacted with both SLE- and RA-derived hybridoma anti-DNA and non-DNA-binding antibodies. These studies indicate that some anti-idiotype antisera may detect specific idiotypes found only on SLE-derived anti-DNA auto-antibodies, whereas other antisera detect shared idiotypes found on both RA and SLE DNA-binding and non-DNA-binding antibodies.

Animals↗