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Biomedical subjects

E C Keystone

Publications and source records attributed to E C Keystone.

At least 37 records · Page 2Linked to original sources

Restricted cytokine expression in rheumatoid arthritis.

OBJECTIVE: To determine the cytokine profile of the phenotypically activated T cell in rheumatoid arthritis (RA) synovium. METHODS: Interleukin-2 (IL-2), IL-2 receptor (IL-2R), IL-6, IL-4, and interferon-gamma (IFN gamma) gene expression was examined in T cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with RA. Estimates of baseline expression were determined using unstimulated peripheral blood (PB) T cells from healthy individuals. The corresponding positive controls were phytohemagglutinin-activated tonsil T cells. RESULTS: In studies of paired PB and SF T cell samples from 17 RA patients, IL-2 messenger RNA (mRNA) levels in only 1 PB and 3 SF samples were more than 2 standard deviations above the mean of levels in unstimulated PB from healthy donors. Similarly, only 5 PB and 7 SF samples exhibited elevated IL-2R mRNA levels. IFN gamma gene expression was not detected in any of the paired RA PB or SF samples. Fractionated T cells from 12 RA ST were screened with similar results: Only 1 of 12 samples exhibited IL-2 mRNA levels more than 2 standard deviations above levels in baseline controls. IL-2R mRNA levels were low or not detected, and IFN gamma mRNA was absent. Subsequent studies showed that IL-4 and IL-6 gene expression levels were also low in RA tissues compared with tonsil T cell-positive controls. CONCLUSION: These data provide evidence for restricted cytokine expression in the T cell population in RA tissues.

Actins

Takayasu arteritis with acute interstitial pneumonia and coronary vasculitis: expanding the spectrum. Report of a case.

We describe the first reported case of Takayasu arteritis presenting as idiopathic adult respiratory distress syndrome, with a pathologic diagnosis of acute interstitial pneumonia. In the same patient, rarely occurring, diffuse coronary vasculitis developed. This case vividly illustrates the extensive, clinically significant vascular involvement that can occur in Takayasu arteritis, as well as the potential extravascular, multisystemic nature of the disease.

Acute Disease

Hormones in self tolerance and autoimmunity: a role in the pathogenesis of rheumatoid arthritis?

Recent studies indicate that pituitary hormones play an important role in immunoregulation. The evidence that endocrine abnormalities are associated with, and may contribute to the development of autoimmune disease is reviewed and discussed. Patients suffering from rheumatoid arthritis show a number of endocrine abnormalities that indicate altered pituitary function. The decreased bioactivity of prolactin and possible inadequate glucocorticoid response to inflammation found in patients may have an etiological role in rheumatoid arthritis. The further clarification of the possible role of endocrine factors in the etiology of autoimmune disease is needed urgently.

Arthritis, Rheumatoid

Systemic vasculitis following influenza vaccination--report of 3 cases and literature review.

Influenza vaccination is a widely accepted practice particularly among the elderly and high risk individuals. Minor and transitory side effects following the vaccination are common while systemic complications are infrequently reported. We describe 3 patients who developed systemic vasculitis following influenza vaccination. With increasing use of influenza vaccination, attention should be drawn to the possible expression of systemic adverse effects such as vasculitis.

Aged

HLA antigens in North American patients with Takayasu arteritis.

OBJECTIVE: To determine the frequency of HLA class I and II antigens in Caucasian North American patients with Takayasu arteritis (TA). METHODS: Seventy-three class I antigens and 13 class II antigens were examined in 21 Caucasian North American patients with TA, and their frequencies were compared with findings in 243 healthy, untreated controls. HLA typing was performed by microlymphocytotoxicity assay. RESULTS: We found no statistically significant positive association of TA with DR2, DR4, DQw3, or any of the other class I or class II antigens studied. A negative association between TA and DR1 was noted. There was no significant association between any of the HLA antigens and the severity of the disease or the presence of complications. CONCLUSION: The negative association between TA and the DR1 antigen suggests that this antigen may be protective against the development of the disease.

Adolescent

Impaired generation of high-affinity interleukin-2 receptors in the autologous mixed lymphocyte reaction in rheumatoid arthritis.

We examined the expression of high-affinity interleukin (IL)-2 receptors (IL-2R) as well as Tac and HLA-DR antigens on peripheral blood (PB) T cells from 11 rheumatoid arthritis (RA) patients and 8 healthy controls induced in the autologous mixed lymphocyte reaction (AMLR). The proportion of HLA-DR- and Tac-bearing T cells and expression of these activation antigens were higher in patients relative to controls (P less than 0.01) in freshly isolated unstimulated PB mononuclear cells. AMLR stimulation of RA T cells failed to induce an increase in the proportion of HLA-DR and Tac-bearing T cells which was observed in health controls. After AMLR stimulation the number of high-affinity IL-2R were significantly lower in RA patients compared with controls (P less than 0.01). The number of high-affinity IL-2R on patient T cells correlated strongly with AMLR reactivity as measured by [3H]thymidine incorporation (r = 0.821, P = 0.002). The results suggest that the AMLR defect in RA may result from impaired generation of high-affinity IL-2R.

Adult

Infections that cause vasculitis.

An infectious cause has long been suspected for most forms of vasculitis. In most cases vascular damage has been ascribed to immune-mediated mechanisms rather than direct microbial toxicity. Evidence cited in this review provides further support for a causal role of infection in the vasculitides by strengthening the link between group A streptococci and hepatitis B virus with polyarteritis nodosa and Kawasaki syndrome. It is anticipated that the application of new molecular technology will provide definitive evidence for the role of infection in the etiopathogenesis of the vasculitides.

Antibodies, Antineutrophil Cytoplasmic

Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis.

We examined the levels of TcR delta 1+ T cells (total gamma delta T cell) and delta TCS1+ (gamma delta T cell subset) T cells in the peripheral blood (PB) and synovial fluid (SF) of 16 patients with rheumatoid arthritis (RA) and compared them to the levels in PB of patients with Felty's syndrome (FS) and 21 healthy control subjects (NML). Synovial fluid from eight patients with seronegative spondyloarthropathies (SSA) was also examined. The results demonstrated elevated levels of the delta TCS1+ subset in the PB of RA and FS patients relative to NML (P less than 0.05). No such differences were observed in the levels of PB TcR delta 1+ T cells. The results did not appear to reflect a non-specific inflammatory response since delta TCS1 T cells were elevated in the SF of RA patients relative to SSA SF and NML PB. delta TCS1 T cells in SSA PB and SSA SF were comparable to NML PB. TcR delta 1+ T cells levels in RA SF were higher than SSA SF levels but were comparable to those of NML PB. Taken together, the results support a pathogenic role for delta TCS1+ T cells in RA.

Antibodies, Monoclonal

Giant cell arteritis presenting as limb claudication. Report and review of the literature.

Upper limb claudication and pulselessness is an uncommon presentation of giant cell arteritis (GCA), often resulting in delayed diagnosis. We describe such a case diagnosed by angiography, in which a temporal artery biopsy showed classic GCA, despite the absence of local signs or symptoms. A review of 26 similar cases revealed that in 81% of patients where the only manifestation of GCA was upper limb findings, temporal artery biopsy yielded positive findings. Steroid therapy clinically improved 24/26 patients. These findings suggest that a consideration of temporal artery biopsy early in the investigation will hasten diagnosis and appropriate therapy.

Aged

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

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