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Biomedical subjects

R M Pope

Publications and source records attributed to R M Pope.

At least 91 records · Page 5Linked to original sources

Lack of circulating immune complexes in uncomplicated erythema nodosum.

There is conflicting evidence in the literature concerning the role of circulating immune complexes (CIC) in the pathogenesis of erythema nodosum (EN). We investigated the possible involvement of CIC in 20 patients with EN, the majority of whom had idiopathic or uncomplicated disease. Immune complexes were detected by 3 complementary radioimmunoassays (the Clq, the mRF, and the anti-C3 solid phase assays). During the presence of the skin lesions, the only abnormalities noted were elevated concentrations of CIC detected by the anti-C3 assay in 5 of the 20 patients. None of the patients had elevated CIC by any of the 3 assays after resolution of skin lesions. These observations do not support a significant role for CIC in the pathogenesis of idiopathic or uncomplicated EN.

Adolescent↗

Evidence for the local production and utilization of immune reactants in rheumatoid arthritis.

Immunoglobulins, including rheumatoid factors, are produced by the rheumatoid synovial membrane. A significant contribution of the synovial membrane to the total IgG and IgM detected in the synovial fluid has been documented. The present study was designed to examine the contribution of the synovial membrane to the rheumatoid factors detected in the synovial fluid. Analysis of the data demonstrated that the synovial membrane was the source of a significant component of the total synovial fluid IgA rheumatoid factor and IgM rheumatoid factor. While some fluids possessed extremely elevated concentrations of the IgG rheumatoid factor, the data suggested that IgG rheumatoid factor was preferentially reduced, relative to total IgG, by the rheumatoid inflammatory process. These observations suggest a potentially important role for IgG rheumatoid factor in rheumatoid synovitis.

Arthritis, Rheumatoid↗

Improved test for IgM antibody to Epstein-Barr virus using an absorption step with Staphylococcus aureus.

The determination of levels of IgM antibody to Epstein-Barr virus (EBV) capsid antigen was improved by absorbing unfractionated test serum with Staphylococcus aureus cells containing protein A. Nonspecific background fluorescence was significantly decreased, thus facilitating the reading of slides and the detection of specific fluorescent reactions in serum with low levels of this IgM antibody. Moreover, the inclusion of the absorption step eliminated false-positive reactions caused by the presence of rheumatoid factor in serum and shortened the time needed for the incubation of test serum with the EBV-infected cell smear. This improved antibody test should facilitate the laboratory diagnosis of acute EBV infections, including unaccompanied by a heterophil antibody response.

Antibodies, Viral↗

The detection of circulating immune complexes and IgG and IgM rheumatoid factors in normal human pregnancy.

The development of immune complexes (IC) and rheumatoid factors (RF) during normal, uncomplicated pregnancy is a controversial issue. Discrepancies in previous reports are due most likely to the different methods used to detect both IC and RF. Using four sensitive radioimmunoassays for immune complexes employing both Clq and mRF and employing sensitive and specific radioimmunoassays for the detection of IgM-RF and IgG-RF, we examined the sera of 35 normal subjects in their third trimester of pregnancy. Immune complex concentrations as measured by four assays were not increased during gestation. However, both IgM-RF and IgG-RF were significantly elevated even though the concentrations of immunoglobulins M and G were virtually identical to the controls. These observations provide further insight into the immunological changes associated with pregnancy. (Am J Reprod Immunol. 2:208-211.)

Antigen-Antibody Complex↗

Detection of antibodies to streptococcal mucopeptide in patients with rheumatic disorders and normal controls.

Bacterial mucopeptide is an integral part of bacterial cell walls and is therefore ubiquitous in our environment. An enhanced degree of humoral immunity has ben detected not only in patients with acute rheumatic fever (ARF), with a known recent response to streptococci, but also in patients with adult and juvenile rheumatoid arthritis (RA and JRA). Our studies confirmed this association with ARF and JRA using a precipitin system as well as a radioimmunoassay to detect IgG anti-mucopeptide antibodies. In those with adult RA, either IgM or IgA rheumatoid factors or IgM or IgA antibodies specific for mucopeptide were responsible for the increased incidence of precipitins to mucopeptide in the RA patients detected in this and other studies. No differences in the specificities of the anti-mucopeptide antibodies were noted between the various patient populations as there were no lines of partial identity or nonidentity when examined by Ouchterlony double diffusion analyses. Additionally, no differences of anti-mucopeptide antibody were observed when the sera from these same patient populations were examined employing inhibition studies utilizing N-acetylglucosamine and rhamnose.

Antibodies, Bacterial↗

Immune complexes in coccidioidomycosis. Correlation with disease involvement.

Circulating immune complexes were quantitated by Clq-binding assays of serum from 73 patients with active coccidioidomycosis, 5 patients with inactive disease, and 34 healthy subjects. Immune complexes were detected in serums of 8 (44%) of 18 patients with active pulmonary disease only and 22 (40%) of 55 patients with active disseminated disease. Results in none of 5 patients with inactive disease and in only 2 (9%) of 34 healthy subjects were positive by the Clq-binding assay. Immune complex levels did not differ in patients with pulmonary disease versus those with disseminated disease. However, immune complexes did correlate with disease involvement. Of 57 patients with coccidioidomycosis involving a single organ system (pulmonary or extrapulmonary), 19 (33%) had immune complexes compared with 6 (67%) of 9 patients with disease involving 2 organ systems, and 5 (71%) of 7 patients with disease of 3 or more organ systems. Immune complex levels correlated with serum IgG, but did not correlate with serum complement-fixing antibody titers to coccidioidin. Rather, the correlation curve between immune complexes and complement-fixing antibody titers yielded a bell-shaped distribution. This distribution pattern suggests that changes in antibody concentration may have effected the size and lattice of immune complexes, resulting in altered detection and/or clearance from the bloodstream.

Antibodies, Fungal↗

Circulating autoantibodies to IgD in rheumatic diseases.

Most mature B lymphocytes possess IgD on their cell surface. Antibodies to IgD produce an adjuvant-like effect in many experimental systems. Employing sensitive class-specific radioimmunoassays, elevated concentrations of autoantibodies to IgD of the IgA, IgM, and IgG classes were detected in the sera of 55% of patients with adult onset rheumatoid arthritis (RA), of 45% with systemic lupus erythematosus (SLE), of 67% with mixed connective tissue disease syndrome (MCTD), and of only 8% of juvenile RA. Marked differences in the class of anti-IgD were noted. An elevated IgA anti-IgD was detected in 45% (p less than 0.01) of RA sera, 27% of SLE sera, and 58% (p less than 0.01) of MCTD sera. IgG anti-IgD was increased in only 26% of RA, 32% of SLE, and 8% of MCTD sera. IgM anti-IgD was elevated in only one patient. IgA anti-IgD was inhibited greater than 90% by IgD but not at all by IgG. Correlations between the concentration of immunoglobulin G and IgA anti-IgD were noted in RA (rs = 0.37, p = 0.02), SLE (rs = 0.46, p = 0.015), and MCTD (rs = 0.4). These data suggest a potential role for autoantibodies to cell surface IgD as modulators of the immune system in some patients with autoimmune disorders.

Antibodies, Anti-Idiotypic↗

Detection and partial characterization of immune complexes in patients with rheumatoid arthritis plus Sjogren's syndrome and with Sjogren's syndrome alone.

In order to characterize the immune complexes detected in patients with Sjogren's syndrome (SS) and with rheumatoid arthritis (RA), the sera of 19 patients with SS alone and 11 with SS plus RA were examined. Elevated quantities of circulating immune complexes (CIC) were detected in 67% by the C1q-binding assay (C1q-BA), 73% by the C1q-solid phase (C1q-SP) assay, 43% by the monoclonal rheumatoid factor solid phase assay (mRF-SP) and 33% by the mRF-inhibition assay (MRF-Inh). Elevated concentrations of IgM RF were detected in 83% and of IgG RF in 73% of the sera by radioimmunoassay. Strong correlations existed between RF of the IgM and IgG classes and both the C1q-BA and the C1q-SP. Three lines of evidence indicated that RF were important components of the immune complexes detected by these radioimmunoassays. These results indicated that in those patients with RA plus SS, as well as those with SS alone, both IgM and IgG RF made substantial contributions to immune complexes detected both by C1q-BA and C1q-SP.

Antigen-Antibody Complex↗

Fatal thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus. Relationship to circulating immune complexes.

An immunologic mechanism, possibly immune complex mediated, has been suggested as the basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP). The evidence supporting this concept has been the association of TTP with systemic lupus erythematosus and the successful therapy of TTP by plasmapheresis. However, most investigators have failed to demonstrate elevated circulating immune complexes during the course of TTP. This report describes a young woman with systemic lupus who developed TTP as a terminal event. Elevated levels of immune complexes were associated with periods of active lupus but were not detectable at the time she developed TTP.

Adult↗

IgG rheumatoid factor: analysis of various species of IgG for detection by radioimmunoassay.

IgM RF is known to react with many species of IgG. This study examined nine species of IgG to determine which was the most sensitive and specific to detect IgG RF by radioimmunoassay. For 19 IgM RF-positive sera, horse IgG was significantly more sensitive than all IgG preparations tested except rabbit IgG. The IgG used include sheep, swine, goat, bovine, and chicken as well as human and baboon Fc. For 22 IgM RF-negative sera from patients with rheumatoid arthritis, only one was positive for IgG RF with rabbit IgG, whereas five were positive with horse IgG. Analysis after preparative ultracentrifugation of a variety of sera positive and negative for IgM RF indicated that horse IgG was more sensitive, whereas rabbit IgG was more specific for the detection of IgG RF by our radioimmunoassay. IgM RF, on the other hand, was more sensitively detected by human Fc than by any preparation other than whole human IgG.

Animals↗

Detection of immune complexes and their relationship to rheumatoid factor in a variety of autoimmune disorders.

The sera of patient with adult rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) were employed together with sensitive radioimmunoassays to examine the relationship between immune complexes detected by three methods and the IgM, IgA and IgG classes of rheumatoid factors (RF). Compared to the controls, significantly increased concentrations of RF and immune complexes were detected for every patient group except JRA. Increased concentrations of IgA RF, IgG RF and immune complexes detected by the C1qBA and the C1qSP were strongly associated with the presence of IgM RF. Significant correlations were noted between RF (especially IgG and IgM) and immune complexes (detected by both the C1qBA and the C1qSP) for patients with RA, SLE and MCTD. These studies suggest that RF may be partially involved in the formation of the immune complexes detected by C1q-binding assays and demonstrate the need for further clarification of the constituents of the immune complexes detected in each disease.

Antigen-Antibody Complex↗

Detection of immune complexes in acute rheumatic fever and their relationship to HLA-B5.

Employing five radioimmunoassays for immune complexes, the sera of 45 acute and 27 postacute follow-up sera from patients with acute rheumatic fever were examined. All patients experienced actue polyarthritis. Complexes were detected in 89% of acute-phase sera by one assay, 51% by two, 29% by three, and 7% by four. Immune complex values decreased significantly at followup, although some abnormalities persisted. There was no correlation between extra-articular manifestations and the occurrence of circulating immune complexes. Those positive for HLA-B5 demonstrated a significantly more pronounced immune response as measured by circulating immune complexes. The data indicate that circulating immune complexes occur frequently in adults with acute rheumatic fever. The relative frequency of immune complexes detected by multiple techniques in B5-positive, compared with B5-negative, patients suggests a genetic basis for the development of immune complexes in these patiemts.

Acute Disease↗

Circulating immune complexes in coccidioidomycosis. Detection and characterization.

Sera of 22 patients with active and 13 with inactive coccidioidomycosis, as well as 15 healthy subjects who were skin-test positive to coccidioidin and 39 healthy subjects who were coccidioidin skin-test negative, were assayed for immune complexes. Circulating immune complexes were measured by the Clq-binding assay, the Clq-solid phase assay, the monoclonal rheumatoid factor inhibition assay, and the monoclonal rheumatoid factor solid phase assay. An increased concentration of circulating immune complexes was detected in 73% of those with active disease by at least one assay compared with 13% of the healthy controls. Significantly increased levels of immune complexes were detected in sera of patients with active coccidioidomycosis by the Clq-binding assay (P < 0.001), the Clq-solid phase assay (P < 0.001), the monoclonal rheumatoid factor inhibition assay (P < 0.005), and the monoclonal rheumatoid solid phase assay (P < 0.05) compared with the results obtained in the 54 healthy subjects. In contrast, those with inactive disease did not show significantly increased concentrations of circulating immune complexes. Sucrose density gradient ultracentrifugation of patients' sera established that the immune complexes were of intermediate size, sedimenting between the 6.6S and 19S markers. Immune complexes were shown to contain both coccidioidin antigen and anticoccidioidin antibody. In addition, a radioimmunoassay was developed to quantitate coccidioidin antigen-containing immune complexes. The latter assay proved highly sensitive in detecting immune complexes in patients with active coccidioidomycosis.

Antibodies, Fungal↗

IgG rheumatoid factor. Relationship to seropositive rheumatoid arthritis and absence in seronegative disorders.

IgG rheumatoid factor was detected in the sera of the majority of patients with seropositive rheumatoid arthritis. Values suggestive of IgG rheumatoid factor were noted in one-quarter of patients with seronegative inflammatory arthropathies. These determinations were always low and correlated with elevated IgG concentrations, suggesting nonspecific adherence of IgG rather than a true antigen-antibody reaction. In support of this conclusion, nonrheumatoid factor IgG was capable of concentration-dependent nonspecific adsorption to the solid phase. IgG, but not IgM, rheumatoid factor corresponded with disease activity in patients with seropositive rheumatoid arthritis, suggesting that IgG rheumatoid factor may be important in the pathogenesis.

Arthritis, Juvenile↗

Rheumatoid factor interference with the latex agglutination test for fibrin degradation products.

The latex agglutination test for FDP is widely employed clinically to aid in the diagnosis of DIC and other conditions. Of sera containing RF, 93% demonstrated positive FDP latex agglutination tests. Reducing agents in all instances destroyed the RF agglutinating capability. Futhermore, 86% of sera positive for FDP and RF became FDP-negative following reduction. Therefore RF was responsible for false-positive FDP latex agglutination tests in the majority of patients. Reduction of patient sera is a rapid, simple method to distinguish a positive FDP test from a false-positive due to RF.

Arthritis↗