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Biomedical subjects

R M Pope

Publications and source records attributed to R M Pope.

At least 73 records · Page 4Linked to original sources
PubMed1989

Antigenic specificity of rheumatoid synovial fluid lymphocytes.

The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone-precipitable MT antigenic complex (AP-MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti-CD3. In patients with RA, the SF proliferative responses to both TT and anti-CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP-MT was significantly increased, compared with PB. SF responses to AP-MT antigens were significantly greater than those to TT. The AP-MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP-MT responsiveness was not restricted to HLA-DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP-MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA.

Acetone↗
PubMed1989

Clinical studies of the reactivity of serum IgG from patients with Graves' ophthalmopathy with porcine orbital tissue preparations.

The clinical utility of ELISA assays for antibodies reactive with a variety of porcine orbital tissue antigen preparations is described using sera from large numbers of patients. Use of such assays does not allow reliable identification of patients with Graves' ophthalmopathy (GO) due to the overlap between patients with and without eye involvement and normal individuals. In 5/6 patients showing high levels of reactivity with porcine eye muscle membrane antigen, a considerable but variable proportion of the binding was found to be species, rather than tissue, specific. No consistent pattern of change in ELISA reactivity with time was seen in studies of serum samples from patients treated medically for hyperthyroidism and patients who received immunosuppressive therapy with cyclosporin A for active, severe ophthalmopathy. Use of previously published ELISA methods using the crude antigen preparations described is therefore not likely to be of use in the routine clinical management of GO patients.

Adult↗
PubMed1989

The use of real-time orbital ultrasound in Graves' ophthalmopathy: a comparison with computed tomography.

Evaluation of the severity of orbital involvement and likelihood of the development of optic neuropathy in Graves' disease can be clinically difficult. We describe the use of real-time orbital ultrasound scanning to measure the medial rectus muscle width in 20 patients with Graves' ophthalmopathy and 21 normal individuals. The normal reference interval (to 2 SDs) was 1.75 to 4.07 mm. Significantly (p less than 0.001; Mann Whitney U-test) larger values were observed in the patients compared with controls, and there was good correlation between medial rectus width and a clinical index of disease severity in individual eyes (p less than 0.001; Spearman rank correlation coefficient). Comparison of the medial rectus measurements obtained using orbital computed tomography and ultrasound showed positive correlation at the p less than 0.001 significance level. Computed tomographic medial rectus measurements also correlated with horizontal and vertical muscle indices for that orbit. We suggest that real-time ultrasound of medial rectus width, using widely available equipment, provides an accurate, simple and non-invasive means of evaluating the orbits of patients with Graves' disease. Repeated measurements may be of value in identifying patients at high risk of visual failure, and in following prospectively the orbital response to therapy in patients with Graves' ophthalmopathy.

Adult↗
PubMed1989

Limited proliferative response to type II collagen in rheumatoid arthritis.

In order to define the potential importance of type II collagen in the activation of rheumatoid arthritis (RA) synovial fluid (SF) lymphocytes, we examined the proliferative response of matched peripheral blood and SF lymphocytes to type II collagen. The mean proliferative response to the collagen was somewhat greater (p less than 0.05) with SF, compared to peripheral blood lymphocytes. However, the magnitude of this response was relatively weak as determined by stimulation indices, and it did not approach that observed with peripheral blood lymphocytes in response to tetanus toxoid. Sixty-seven percent of peripheral bloods and 50% of SF demonstrated positive responses to the control antigen, tetanus toxoid. In contrast, only 6 and 28%, respectively, were positive in response to type II collagen. The addition of exogenous interleukin 2 augmented responses to the tetanus toxoid, however, no such enhancement with type II collagen was noted in our patients. Our collagen was arthritogenic in experimental animals. These observations do not support the existence of T cell specificity toward type II collagen as a common mechanism for the expansion of synovial lymphocytes in RA.

Adult↗
PubMed1988

Increased helper inducer and decreased suppressor inducer phenotypes in the rheumatoid joint.

Cells isolated from the joints of patients with rheumatoid arthritis (RA) exhibit functional immune abnormalities, such as diminished suppressor activity, depressed response to mitogens, and enhanced immunoglobulin production. We sought to characterize the T lymphocyte subsets in the synovial fluid (SF) and peripheral blood (PB) of RA patients in an attempt to clarify the mechanism(s) responsible for these functional immune abnormalities. We used dual-immunofluorescence staining techniques with several combinations of monoclonal antibodies, including anti-4B4 and anti-2H4, which define, respectively, the helper inducer and suppressor inducer subsets of CD4+ (Leu-3+ and T4+) cells. Mononuclear cells from normal PB (n = 9), RA PB (n = 6), and RA SF (n = 9) were analyzed, after staining, by flow cytometry. We observed a significant increase (P less than 0.0002) in the number of cells bearing the helper inducer phenotype (CD4+, 4B4+), and a significant decrease (P less than 0.0002) in the number of cells bearing the suppressor inducer phenotype (CD4+, 2H4+), in RA SF compared with the levels in PB from RA patients or normal control subjects. We also observed that the CD8+, 2H4+ subset was significantly decreased (P less than 0.0001) in SF compared with that in PB. There was no significant difference in the lymphocyte subset levels in PB from RA patients and from normal subjects. These observations may account, in part, for the reduced suppressor activity, the poor response to mitogens, and the autologous mixed lymphocyte reaction, as well as the enhanced production of Ig and rheumatoid factor, that are observed in the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1987

Serum-mediated suppression of lymphocyte transformation responses in coccidioidomycosis.

Lymphocyte transformation (LT) responses to coccidioidin (CDN) and spherulin were suppressed in 11 (73%) of 15 patients with active coccidioidomycosis when their mononuclear cells were assayed in autologous serum as compared to serum from healthy, CDN skin test-positive subjects. Suppressed LT responses were specific for Coccidioides immitis antigens in 7 (64%) of the 11 patients. Immunoaffinity chromatography of patient sera with Staphylococcus protein A adsorbed the suppressor component(s) and thereby established that suppression was attributed to immunoglobulin G, either alone or complexed with antigen. The possibility that suppression was mediated by immune complexes was examined by adding complexes formed in vivo or in vitro to mononuclear cell cultures of healthy CDN-reactive persons before LT assays. Although complexes prepared in this manner were reactive in an enzyme-linked immunosorbent assay designed to detect Coccidioides antigen-specific immune complexes, no suppression of LT responses was observed. We conclude that serum-mediated suppression of LT responses in coccidioidomycosis is attributed to monomeric and not immune-complexed immunoglobulin G antibody.

Antigen-Antibody Complex↗
PubMed1986

Modulation of spontaneous immunoglobulin production by natural killer cells in rheumatoid arthritis.

Synovial fluid (SF) mononuclear cells obtained from patients with rheumatoid arthritis (RA) spontaneously produce large amounts of immunoglobulin. In the rheumatoid joint, natural killer (NK) cell activity is reduced in comparison with that in the peripheral blood (PB). We examined the ability of SF NK cells to modulate the spontaneous production of Ig in RA SF, and we contrasted this with the activity in PB from RA patients and from normal subjects. We found that the spontaneous production of IgG was greater in RA SF than in RA or normal PB. The baseline NK activity was significantly lower in RA SF than in RA or normal PB (P less than 0.005). Incubation with anti-Leu-11b and complement reduced NK activity in PB, but not in SF, and it significantly (P less than or equal to 0.021) increased IgG production in both RA SF and RA PB. Lysis of NK cells in this manner also resulted in a significant increase (P less than 0.02) in IgM production in RA SF. These results suggest that NK cells with a Leu-11b phenotype down-regulate the ongoing synthesis of IgG and IgM in the rheumatoid joint.

Adult↗
PubMed1986

Differential effects of therapeutic regimens on specific classes of rheumatoid factor.

This study was performed to define further the relationship of circulating IgM and IgG rheumatoid factor to the articular manifestations of rheumatoid arthritis. Patients with substantial clinical improvement (greater than 55%) or no improvement or worsening were chosen for study. Patients were further selected to include those treated with non-steroidal anti-inflammatory drugs (NSAIDs) alone, or NSAIDs plus D-penicillamine or gold. Significant reductions of IgM (p less than 0.001) and IgG (p less than 0.005) rheumatoid factor were seen only in those treated with gold who improved clinically. These observations suggest that in patients experiencing comparable degrees of clinical improvement the simultaneous alterations of circulating IgG and IgM rheumatoid factor observed are dependent upon the therapeutic regimen employed.

Adult↗
PubMed1985

Regulation of T cell proliferation by cloned interferon-alpha mediated by Leu-11b-positive cells.

The autologous T lymphocyte proliferative response (AMLR) induced by a B lymphocyte-enriched non-T, nonadherent cell population (NT, NAC) and by a macrophage-enriched population were both suppressed by the addition of a cloned interferon-alpha (IFN-alpha Con1) directly to the cultures. Preincubation of the stimulating NT, NAC with IFN-alpha Con1 resulted in comparable suppression. In contrast, preincubation of the macrophages with IFN-alpha Con1 resulted in significant augmentation of T cell proliferation. Depletion of Leu-11b-positive cells from the NT, NAC exposed to IFN-alpha Con1 restored the autologous T cell response. Addition of IFN-alpha Con1 activated Leu-11b-positive cells, isolated from the NT, NAC population, was suppressive of the AMLR. Although NK cytotoxicity was irradiation sensitive, suppression of the AMLR by IFN-alpha Con1-activated NT, NAC was resistant, suggesting that different subsets of cells or mechanisms by the same cells may have been responsible. These observations may offer insights into the potential role of cells with the NK phenotype, Leu-11b, and IFN in contributing to immuno-regulatory changes observed in clinical states associated with elevated concentrations of IFN.

Antibodies, Monoclonal↗
PubMed1985

Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood.

Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.

Adult↗
PubMed1984

Characterization of the defective autologous mixed lymphocyte response in rheumatoid arthritis.

In order to characterize the autologous mixed lymphocyte response (AMLR) in patients with rheumatoid arthritis (RA) and to define the relationship with disease activity, peripheral blood T lymphocytes were stimulated with either a B lymphocyte-enriched (B cells) or a macrophage-enriched (macrophages) population. A significant reduction (P less than 0.01 to P less than 0.001) of T cell proliferation stimulated both by B cells and macrophages was observed in patients with active disease. The B lymphocytes were significantly less stimulatory (P less than 0.02 to P less than 0.001) than macrophages in the patients compared with the controls. In the normal controls, macrophages in higher concentrations were capable of suppressing the B lymphocyte-stimulated AMLR, but macrophages from patients with RA were not excessively suppressive. A significant association (P less than 0.02) was observed between disease activity and the AMLR. Using the B-enriched population, the AMLR proliferative response was significantly associated (P less than 0.001) with the production of interleukin-2. Defects in proliferation could only be partially restored by the addition of interleukin-2. These data indicate that the defective AMLR observed in patients with RA is related to disease activity and is associated with altered cellular interactions among T lymphocytes, macrophages, and the B lymphocyte-enriched population.

Arthritis, Rheumatoid↗
PubMed1983

Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis.

Rheumatoid arthritis is associated with circulating and intra-articular immune complexes and rheumatoid factors. The clinical activity of rheumatoid arthritis improves during pregnancy in the majority of women, with exacerbation following delivery. Concentrations of immune complexes, as detected by the Clq-binding assay, the Clq-solid phase assay, and the monoclonal rheumatoid factor-solid phase assay, decreased during gestation, with elevations following delivery. Concentrations of IgM-rheumatoid factor and IgG-rheumatoid factor, analyzed by radioimmunoassay, changed variably during pregnancy, increasing in some patients and decreasing in others. When examined serially before, during, and following pregnancy, changes in the concentration of circulating immune complexes and/or rheumatoid factors corresponded with the clinical changes in three patients. These observations document the significant effect of gestation on the concentration of circulating immune complexes in patients with rheumatoid arthritis. They also support the role of these laboratory tests in monitoring the clinical course of rheumatoid arthritis.

Antigen-Antibody Complex↗
PubMed1983

Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases.

Isoprinosine (IPS) is a new anti-viral agent which appears to have immunomodulatory activities which include its ability to enhance the in vitro blastogenic responses of normal lymphocytes to mitogens. The present study compares the effects of IPS on the in vitro immune functions of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients with its effects on PBMC from normal controls. Each mitogen (Con A, PHA or PWM) was used at its optimal concentration with a range of IPS concentrations (0-25 micrograms/ml). PHA-induced blastogenesis by PBMC from all three groups was enhanced by IPS at or above 5 micrograms/ml. The Con A-induced responses of SLE lymphocytes were significantly enhanced over controls by IPS (P less than 0.02 at 5 micrograms/ml) while those of RA lymphocytes were not. IPS had little effect on PWM-induced blastogenesis by RA lymphocytes but did enhance the blastogenic responses of SLE lymphocytes (P less than 0.01 at 5 micrograms/ml). In contrast, the characteristically high immunoglobulin synthesis by SLE lymphocytes was decreased by IPS. The mechanism responsible for these effects is not known but IL-2 production by patient lymphocytes in vitro which was low for both RA (P less than 0.01) and SLE (P less than 0.02) increased significantly (P less than 0.05) when SLE lymphocytes were cultured with IPS. These data identify IPS as an agent for the study of aberrant immune regulation in autoimmune diseases and suggest that it may have potential therapeutic value in SLE.

Adult↗
PubMed1983

Relationship between the articular manifestations of rheumatoid arthritis and circulating immune complexes detected by three methods and specific classes of rheumatoid factors.

Although detected in most patients with rheumatoid arthritis (RA), the relationship of the concentration of circulating immune complexes and specific classes of rheumatoid factors (RF) to the activity of the articular manifestations is uncertain. Therefore, 57 patients were evaluated in a prospective fashion. Combining all data, the concentration of IgG RF and the erythrocyte sedimentation rate (ESR) correlated most strongly with the articular index (Pc less than 10(-4], while the concentrations of IgM RF and IgA RF did not correlate. The quantity of immune complexes detected by the C1q-SP and the mRF-SP assays correlated significantly with articular manifestations (Pc less than 0.02 and less than 0.002) while those detected by the C1q-BA did not. Strong associations between the change of the articular index and both the change of ESR (r = 0.76, Pc less than 0.007) and the change of IgG RF (r = 0.72, Pc less than 0.014) were noted in those begun on remittive agents during the course of this investigation. Of the assays for immune complexes, changes of those detected by the C1q-SP correlated most closely with the articular index (r = 0.63) in this group. These observations support a potential role for the selective use of certain laboratory parameters, in addition to the ESR, in monitoring the articular activity of certain patients with RA.

Adult↗