Leukocytoclastic vasculitis with HIV infection.
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Adult↗
Biomedical subjects
E C Keystone
Publications and source records attributed to E C Keystone.
Erythema nodosum and non-Hodgkin's lymphoma.
We describe a case of erythema nodosum associated with non-Hodgkin's lymphoma. The course and resolution of the erythema nodosum correlated most closely with a breakdown and release of new antigen at the start of a new regimen of chemotherapy.
Adult↗
Serial levels of soluble interleukin 2 receptor in the peripheral blood of patients with rheumatoid arthritis: correlations with disease activity.
We serially assayed soluble interleukin 2 receptor (sIL-2R) levels in the peripheral blood (PB) of 22 patients with rheumatoid arthritis (RA) followed for a period of 12 months, and correlated these levels with disease activity. We examined the relationship between the direction in which each of the disease measures changed between assessments and the direction of change in sequential sIL-2R levels. In 22 of the 25 (88%) instances where there was a 30% change in the active joint count between sequential assessments, the direction of change of the PB sIL-2R level was found to be in parallel (chi 2 = 11.7, p less than 0.008). Our results suggest that serial sIL-2R levels are a useful means of confirming clinically significant changes in disease activity in patients with RA, irrespective of therapy.
Anti-Inflammatory Agents↗
Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: a common feature of autoimmune disease.
We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders.
Adult↗
Impaired autologous mixed lymphocyte reaction (AMLR) reactivity of peripheral blood T cell subsets in rheumatoid arthritis.
We examined AMLR reactivity of unseparated T cells and CD4+ and CD8+ T cell subsets in peripheral blood from 11 rheumatoid arthritis (RA) patients and 10 healthy controls. T cell subsets were isolated by negative selection using complement mediated cytotoxicity. AMLR reactivity of six patients (designated RA-L was reduced below the range of the controls' responses. Five patients (designated RA-N) exhibited normal AMLR reactivity. We observed impaired AMLR reactivity of CD4+ T cells from RA-L relative to RA-N and healthy controls (P < 0.05). CD4+ T cell reactivity of RA-L was reconstituted to normal with pharmacological doses of recombinant interleukin-2 (IL-2) (100 U/ml). In contrast, CD8+ T cells from RA-L in the presence of 100 U/ml IL-2 exhibited markedly impaired AMLR reactivity relative to RA-N and healthy controls (P < 0.05). Dose-response studies revealed partial reconstitution of CD4 T cells with physiological concentrations of IL-2 (10 U/ml). To examine the possibility that in vivo pre-activation of T cells in RA accounted for the findings, T cells or subsets were cultured alone for 7 days in the presence of 100 U/ml IL-2. A trend toward enhanced reactivity of CD4+ and CD8+ T cells in L-RA relative to N-RA and healthy controls was observed, but the differences were not statistically significant. There was no correlation between reactivity of T cells alone in the presence of IL-2 and AMLR reactivity. The results suggest the possibility that abnormal AMLR reactivity of CD4+ and CD8+ T cell subsets in RA may arise as a consequence of different pathophysiological mechanisms.
Adult↗
Elevated soluble interleukin-2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis.
In a previous study, we used an enzyme-linked immunosorbent assay to measure soluble human interleukin-2 receptors (IL-2R), and found that when activated lymphocytes produce cell-associated IL-2R, they also release a soluble form of IL-2R into culture supernatants in vitro. Soluble IL-2R have also been detected circulating in vivo at low levels in the serum of healthy individuals, and at abnormal levels in a variety of diseases, particularly those where immune dysfunction is thought to play an important role. We therefore evaluated serum IL-2R levels in 77 patients with rheumatoid arthritis (RA), and compared them with levels in 46 age-matched healthy controls. Nineteen additional RA patients with concurrently obtained sera and synovial fluid (SF) samples were compared with 14 patients with osteoarthritis of the knee or hip. The serum IL-2R levels were significantly elevated in RA patients, compared with the control groups (P less than 0.0001). Serum IL-2R levels in the RA patients did not correlate with disease activity as determined by a variety of clinical and laboratory parameters. RA SF IL-2R levels were significantly higher than corresponding RA serum IL-2R levels (P = 0.0001). No such difference was noted in the osteoarthritis group, where serum and SF IL-2R levels were comparable with serum levels in healthy controls. These findings support the hypothesis that in vivo lymphocyte activation plays an important role in RA; moreover, soluble IL-2R measurement in serum and SF may be a very useful way to identify patients at risk for, or manifesting, a chronic immune-mediated inflammatory arthropathy.
Anti-Inflammatory Agents, Non-Steroidal↗
Structure of T cell antigen receptor beta chain in synovial fluid cells from patients with rheumatoid arthritis.
We attempted to identify a clonal proliferation of T cells from synovial fluid samples from patients with rheumatoid arthritis, using techniques of restriction fragment length polymorphism. We used probes for the beta chain of the T cell receptor to analyze restriction fragments prepared from the genomic DNA of synovial fluid mononuclear cells from 10 patients and synovial fluid T cell preparations from 5 additional patients. The results demonstrated unarranged (germline) T cell receptor gene fragments of DNA in all cell preparations, indicating the lack of clonality of rheumatoid arthritis synovial fluid T cells.
Arthritis, Rheumatoid↗
Reactivity of T-cells from patients with rheumatoid arthritis to anti-CD3 antibody.
The ability of an anti-CD3 monoclonal antibody (OKT3) to induce proliferation was examined in peripheral blood mononuclear cells (PBM) from 30 patients with rheumatoid arthritis (RA). Controls consisted of 10 patients with osteoarthritis, 12 patients with psoriatic arthritis, and 12 healthy subjects. The results revealed enhanced PBM reactivity in patients with active RA relative to inactive RA patients and all control groups. PBM of patients with mild/moderate clinical disease activity exhibited augmented anti-CD3 reactivity while those with severe disease demonstrated impaired reactivity. Enhanced reactivity was also observed in the active RA group using another anti-CD3 monoclonal antibody (Leu-4). Differences in anti-CD3 dose-response or time kinetics could not account for the results. Studies of enriched T-cell preparations revealed a markedly enhanced anti-CD3 reactivity of RA T-cells relative to normal control T-cells. Monocyte/T-cell mixing experiments revealed no enhanced reactivity of RA monocytes in the anti-CD3 response. RA T-cell preparations depleted of monocytes by limiting dilution reacted significantly more to anti-CD3 in the presence of IL-2 relative to controls. The enhanced reactivity could be accounted for in part by hyperreactivity of the OKT8-bearing subpopulation of T-cells.
Antibodies, Monoclonal↗
Serum phospholipase A2 correlates with disease activity in rheumatoid arthritis.
We previously demonstrated a marked elevation of the proinflammatory enzyme phospholipase A2 (PLA2) in all synovial fluids and some sera of patients with rheumatoid arthritis (RA). Since PLA2 was found to induce inflammatory changes in the skin and joints of experimental animals, we tested whether the serum level of PLA2 correlates with the clinical activity of RA. In the group of 51 patients with classical or definite RA, 13 (25%) had high serum levels of PLA2 (over 2 standard deviations above the normal mean). Comparison of clinical disease activity in patients with high levels of PLA2 with those with normal PLA2 levels showed that patients with high PLA2 levels had a significantly higher joint count, more swollen joints, much higher Landsbury index, lower functional class, lower hemoglobin, lymphopenia and higher erythrocyte sedimentation rate (ESR). To more accurately assess the relationship between the PLA2 level and disease activity in RA, we formulated 2 indices. Clinical index consisted of the Landsbury index, number of swollen joints and duration of morning stiffness. Laboratory index consisted of hemoglobin, absolute number of peripheral blood lymphocytes, platelet count and ESR. Our results showed that both indices correlated strongly with PLA2 activity (p less than 0.0001). The results support the hypothesis that PLA2 plays a pathogenetic role in RA and suggest that serum PLA2 levels may serve as an additional measure of disease activity.
Adult↗
HLA-DR4 in giant cell arteritis: association with polymyalgia rheumatica syndrome.
Forty-three patients with well-documented giant cell arteritis (GCA) were studied clinically and with HLA typing. All patients were over age 40. Twenty-two of the patients had coexistent polymyalgia rheumatica (PMR). No association with class I HLA antigens was detected. When compared with HLA findings in 243 healthy controls, HLA-DR4 was increased in patients with GCA and PMR, but not in patients with GCA alone. Pooled analysis of data from 4 published papers confirmed the association of DR4 with GCA and PMR (P much less than 0.00001). Patients with PMR but negative findings of temporal artery biopsies also showed an increased frequency of HLA-DR4, but this did not reach statistical significance, probably because of the small number of subjects. It is likely that the increased frequency of DR4 in GCA patients is related to its association with PMR.
Adult↗
Significance of anticentromere antibody in idiopathic Raynaud's syndrome.
Fifty-eight patients with Raynaud's syndrome who had no evidence of definite underlying connective tissue disease had serum analyzed for the presence of anticentromere antibody using indirect immunofluorescence techniques on HEp-2 cell lines. Eighteen patients (31 percent) were anticentromere antibody-positive. The anticentromere antibody-positive group demonstrated significantly more frequent digital telangiectases, digital edema, elevated levels of immunoglobulins, and low C4 values. Photoplethysmography revealed significantly diminished blood flow in the anticentromere antibody-positive group. Capillary microscopy revealed significantly increased avascularity and number of dilated loops in the anticentromere antibody-positive group. Giant loops were seen exclusively in the anticentromere antibody-positive group. The clinical findings in the anticentromere antibody-positive group are suggestive of a transition to a connective tissue disease with features of the CREST syndrome.
Adult↗
Origin of defective T lymphocyte-suppressor activating factor interaction in patients with rheumatoid arthritis.
We previously examined the generation of T cell released suppressor activity (TRSA) from peripheral blood T cells from patients with rheumatoid arthritis (RA) in response to a soluble suppressor activating factor (SAF) produced by a 6-thioguanine resistant mutant of the human T cell line CEM. We reported (Lau et al., 1985 Clin. exp. Immunol. 61, 481) that T cells from a substantial proportion of RA patients exhibited impaired TRSA release. To delineate further the TRSA abnormality observed in patients with active RA, we evaluated the kinetics of SAF activation, precursor frequency of SAF reactive cells and quantity of activated SAF released on a per cell basis. The results showed that a lower precursor frequency of SAF reactive cells accounted for defective TRSA release in a majority of RA patients, while TRSA release on a per cell basis was normal. The defective TRSA response to SAF could not be explained by abnormal dose kinetics of SAF, time kinetics of TRSA release or prior in vivo lymphocyte activation of the RA T cells.
Adult↗
Lymphocytotoxins in vasculitis. Correlation with clinical manifestations and laboratory variables.
Twenty-eight of 53 patients with various types of vasculitis were found to have cold reacting lymphocytotoxins (LCT). LCT were cytotoxic to both peripheral blood B and T cells as well as to OKT4 and OKT8 subpopulations. The interaction with the B cells was more pronounced than with the T cells as shown by reactivity with the former at higher serum dilutions than with the latter. Similar results were obtained with eluates from the unseparated lymphocytes and from B or from T cells. Partial purification of LCT demonstrated that they belong to the IgM class. LCT correlated with the level of circulating immune complexes as determined by the fluid phase C1q binding assay, but they did not correlate with the level of immunoglobulins, complement or antinuclear factors. The presence of LCT correlated significantly with the activity but not with the disease duration or the number of involved organs. Correlation of LCT with the activity of vasculitis implies that these cytotoxins may have a pathogenetic role and perhaps may serve as a marker for disease activity.
Antigen-Antibody Complex↗
In vivo activation of lymphocytes in rheumatoid arthritis.
Spontaneous in vivo proliferation of peripheral blood mononuclear cells (PBM) and T and B lymphocytes from 28 patients with rheumatoid arthritis (RA), 20 healthy individuals and 13 patients with psoriatic arthritis was evaluated. PBM, T (E+) and non-T (E-) cells from patients with active RA proliferated significantly more than the same populations from healthy individuals and patients with inactive RA. In contrast, only E+ cells from PSA patients showed a trend to increased proliferation relative to healthy individuals. AET treated sheep red blood cells (SRBC) inhibited 3HTdR incorporation of highly profilerating PBM of active RA patients. The data suggest in vivo activation of both B and T cells in patients with clinically active RA.
Adult↗
Enhanced interleukin 1 generation by monocytes in vitro is temporally linked to an early event in the onset or exacerbation of rheumatoid arthritis.
Twenty-one patients with rheumatoid arthritis (RA) and 12 age and sex matched healthy controls were examined for the ability of their monocytes (adherent cells, AC) to spontaneously secrete interleukin 1 (IL-1) and for their peripheral blood mononuclear cells (PBMC) to secrete interleukin 2 (IL-2) induced by Staphylococcal Protein A (SPA). All RA patients had PBMC which secreted normal amounts of mitogen induced IL-2 regardless of disease activity or disease history. However, AC from RA patients who had a recent (less than 6 months) onset of their disease, or exacerbation of existing RA, had enhanced spontaneous IL-1 secretion. AC from patients with equally active RA but with historically stable disease generated normal amounts of IL-1. Enhanced in vitro IL-1 generation by circulating monocytes is temporally linked to an early event in the onset of exacerbation of RA.
Acute Disease↗
Interleukin 1 and interleukin 2 generation by peripheral blood cells from patients with ankylosing spondylitis.
We examined the spontaneous secretion of interleukin 1 (IL-1) from peripheral blood monocytes and staphylococcal protein A (SPA) induced secretion of interleukin 2 (IL-2) from peripheral blood mononuclear cells from 13 patients with active ankylosing spondylitis and 10 healthy controls. IL-1 and IL-2 secretion in the patient group was not measurably different from controls (p greater than 0.05). We also examined IL-1 and IL-2 generation in 7 patients before and 2 months after therapy with a nonsteroidal antiinflammatory agent, piroxicam. A variable effect of piroxicam was observed on IL-1 and IL-2 generation despite the efficacy of piroxicam in reducing the clinical activity of the disease. Our results suggest the absence of an intrinsic aberration in IL generation from peripheral blood cells from patients with ankylosing spondylitis.
Adult↗
Nifedipine in the treatment of idiopathic Raynaud's syndrome.
Thirty-nine patients with idiopathic Raynaud's syndrome were randomized into a double-blind controlled trial comparing nifedipine 10 mg TID to placebo during the winter months between November, 1981 and March, 1983. The pills were doubled at 5 weeks in the absence of subjective improvement. Frequency and severity of vasospastic attacks were recorded in a diary. Over the 10-week treatment period, there was a 48.2% reduction in frequency of attacks in the nifedipine group compared to a 24.6% reduction in the placebo group (p less than 0.05). Treatment reduced the frequency of attacks by at least 30% in 10 of 15 patients. The severity of attacks was also significantly improved. Further, analysis suggests a trend towards diminished effectiveness over time. Side effects occurred in all patients taking nifedipine but were usually mild and well tolerated. Nifedipine is effective in reducing the frequency and severity of vasospastic attacks in idiopathic Raynaud's syndrome over a 10-week period.
Adult↗
Digital blood flow and nailfold capillary microscopy in Raynaud's phenomenon.
Digital blood flow was assessed by photoplethysmography, ultrasonic arterial flow tracing and measurement of systolic blood pressure, and compared to nailfold capillary microscopy in 20 normal controls, 16 patients with primary Raynaud's phenomenon, 40 with undifferentiated connective tissue disease and 30 with systemic sclerosis. All 4 measurements showed significant differences between controls, Raynaud's phenomenon and systemic sclerosis but only capillaroscopy (mean number of enlarged capillary loops and avascular score) was able to differentiate between primary Raynauds and undifferentiated connective tissue disease. Capillaroscopy (mean numbers of enlarged capillary loops) was the most sensitive (100%) and specific (81%) test with a positive predictive value of 90% for systemic sclerosis.
Adult↗