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Biomedical subjects

J Sieper

Publications and source records attributed to J Sieper.

At least 199 records · Page 11Linked to original sources
PubMed1993

The possible role of Shigella in sporadic enteric reactive arthritis.

Reactive arthritis (ReA) occurs after a urogenital infection usually with Chlamydia trachomatis or an enteritis due to Yersinia, Salmonella, Campylobacter or Shigella, Shigella, except during epidemics, is not considered to be a frequent cause of enteric reactive arthritis. However this might be due to the lack of a reliable antibody test, which makes diagnosis difficult. We compared synovial and peripheral blood lymphocyte proliferation to various bacterial antigens in 19 consecutive patients with ReA or undifferentiated oligoarthritis. In five patients Shigella was identified as the causative microbe by a specific synovial lymphocyte proliferation. All five patients had a history of symptomatic diarrhoea and had negative stool cultures by the time arthritis developed. Four of the five were HLA B27 positive. We conclude that Shigella may be underestimated as a cause of non-epidemic ReA.

Adult↗
PubMed1993

T cells are responsible for the enhanced synovial cellular immune response to triggering antigen in reactive arthritis.

In reactive arthritis (ReA) there is specific proliferation of synovial fluid (SF) mononuclear cells (MNC) to the triggering bacterial antigen; comparatively little or no response is seen in peripheral blood (PB). To investigate the mechanism of this elevated local immune response, we examined patients with typical ReA who showed an enhanced antigen-specific synovial immune response in bulk culture. Using separated fractions of T cells and antigen-presenting cells (APC) from PB and SF we showed that the synovial T cells rather than SF APC are responsible for the specific proliferation. By limiting dilution analysis, the frequency of T cells responding to the specific antigen was found to be significantly increased compared with the frequency of irrelevant antigen-specific T cells. Furthermore, the frequency of T cells responding to the specific antigen was higher in SF (between 1/619 and 1/4846, mean 1/2389) than in PB (between 1/1286 and 1/16,279, mean 1/7350). We conclude that the specific synovial cellular immune response in ReA is mainly due to an expansion of antigen-specific T cells within the joint. However, the non-specific hyper-reactivity of SF T cells and differences between SF and PB APC may make a more minor contribution.

Adult↗
PubMed1993

Analysis of cytokine profiles in synovial T cell clones from chlamydial reactive arthritis patients: predominance of the Th1 subset.

Subpopulations of human T cells (Th0, Th1 and Th2) can be distinguished by their cytokine-secretion pattern. Evidence is increasing from other studies that the outcome of a human disease may depend on the subpopulation of T cells that predominates at the site of inflammation. Reactive arthritis serves as a useful model of chronic inflammatory diseases, because the triggering antigen can be identified. Using this triggering antigen we raised 33 T cell clones reactive with Chlamydia trachomatis and 25 T cell clones that were not reactive, all from the synovial fluid of two patients suffering from Chlamydia-induced arthritis. Their cytokine secretion patterns for interferon-gamma (IFN-gamma), IL-2 and IL-4 were analysed, as also were mRNAs for IFN-gamma and IL-10 by in situ hybridization. Out of the 33 antigen-reactive clones 23 showed a Th1 pattern with IFN-gamma but not IL-4 secretion, while the remaining 10 exhibited a Th0 pattern. The clones that did not react with Chlamydia expressed all patterns of cytokine secretion, including a Th2 pattern, thus providing a control population that excludes bias in the sampling procedure. CD4 and CD8 clones displayed a similar cytokine-secretion pattern. In addition this study demonstrates for the first time the expression of IL-10 mRNA in T cell clones derived from synovial fluid, and this was not confined to the Th2 subset. The Th1 response that Chlamydia provoke can be regarded as appropriate for such an obligate intracellular pathogen.

Adult↗
PubMed1992

[Quantitatively evaluated dynamic magnetic resonance tomography in chronic polyarthritis of the knee joint. A therapeutic follow-up after intra-articular cortisone application].

32 patients with chronic polyarthritis were examined by MRT. Following intra-articular application of 25 mg prednisolone, 18 patients were re-examined after two of three weeks and 7 out of 18 patients were re-examined after 8 to 16 weeks, both by MRT and clinically. After an initial double echo sequence, we carried out a dynamic series of FLASH measurements (TR 30, TE 10 ms, 70 degrees) following an intravenous bolus of 0.1 mmol gadolinium-DTPA. Single intensity-time curves were treated quantitatively in relation to the pannus, muscles and effusions. Two or three weeks after treatment the curve parameters showed a reduction in pannus vascularisation which remained constant for the 8 to 16 weeks of further observation. Contrast diffusion in the pannus is initially reduced but approaches the early measurements at the time of the second examination.

Adult↗
PubMed1992

Alteration in T cell/macrophage ratio may reveal lymphocyte proliferation specific for the triggering antigen in reactive arthritis.

It has previously been shown that synovial fluid (SF) mononuclear cells (MNC) from patients with reactive arthritis (ReA) and some patients with undifferentiated oligoarthritis (UOA) respond specifically to the triggering bacterium (specific responders). However, in some patients there is a response to two or more bacteria (non-specific responders) and in a third group no response is found (non-responders). We assessed whether the proportion of synovial MNC which were macrophage-monocyte (MaMo) differed among the specific responder, non-specific responder and non-responder groups. There was no difference between the specific (33 +/- 9) and the non-specific (32 +/- 26) groups; non-responders had a higher percentage of MaMo (61.3 +/- 31%) although the difference was not significant. We also investigated whether the specificity of the response to antigen in ReA or UOA SF was altered by changing the T-cell/MaMo ratio. In all five specific responders the immune response remained specific whatever the ratio tested. However, four of the five non-specific responders, but none of the non-responders, developed a specific response to one of the tested antigens by increasing the T cell/MaMo ratio. We conclude that in some patients with a non-specific response, alteration of the T cell/MaMo ratio uncovers a specific response which may identify the triggering antigen.

Adult↗
PubMed1992

Aetiological role of bacteria associated with reactive arthritis in pauciarticular juvenile chronic arthritis.

BACKGROUND: The cause of juvenile chronic arthritis (JCA) is unknown. Pauciarticular JCA is the most common subtype and can be subdivided into early (type I) and late onset (type II) forms, the latter clinically resembling reactive arthritis. METHODS: The cellular immune responses to bacteria associated with reactive arthritis in blood and synovial fluid from 39 children with pauciarticular JCA, three children with classical reactive arthritis, and two children with psoriatic arthritis were examined. Specific titres of antibodies to bacteria in serum samples were measured in all patients. RESULTS: A bacteria specific synovial cellular immune response was found in two of three (67%) patients with reactive arthritis and 14 of 28 (50%) patients with pauciarticular JCA type II but only in one of 11 (9%) patients with pauciarticular JCA type I and none in patients with psoriatic arthritis. Six patients responded specifically to Chlamydia trachomatis and 11 to Yersinia enterocolitica. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. CONCLUSIONS: These findings suggest that bacteria with associated reactive arthritis may have a causative role in pauciarticular JCA type II but not in JCA type I.

Adolescent↗
PubMed1992

Cellular immunity to cartilage proteoglycans: relevance to the pathogenesis of ankylosing spondylitis.

Cellular immunity to cartilage proteoglycans may be responsible for sustaining chronic inflammation in ankylosing spondylitis. This hypothesis was examined by measuring peripheral blood and synovial fluid mononuclear cell proliferation in five preparations of human cartilage proteoglycan monomer in vitro. Peripheral blood mononuclear cells from 25 patients and synovial fluid mononuclear cells from five patients were compared with those from normal and disease control subjects matched for age. No significant differences were found between the three groups. This suggests that autoimmune responses to cartilage proteoglycans are unlikely to play a significant part in the pathogenesis of ankylosing spondylitis.

Adult↗
PubMed1992

Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis.

We studied the cellular and humoral immune response to Chlamydia trachomatis, Yersinia enterocolitica and Borrelia burgdorferi in paired samples of peripheral blood and synovial fluid (SF) in undifferentiated oligoarthritis, reactive arthritis (ReA) and rheumatoid arthritis. Antigen specific lymphocyte proliferation was found in SF of 43% of patients with ReA and 34% of patients with undifferentiated oligoarthritis. C. trachomatis was the most frequent single agent. HLA-B27 was positive in 83% of patients with ReA and in 62% of patients with undifferentiated oligoarthritis with antigen specific lymphocyte proliferation. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. Only chlamydial antigen was detected in SF cells using monoclonal antibodies. We conclude that some patients with undifferentiated oligoarthritis may have a forme fruste of ReA. This finding is important in view of recent evidence supporting the efficacy of antibiotic therapy in ReA.

Adult↗
PubMed1992

HLA-DP restricted Chlamydia trachomatis specific synovial fluid T cell clones in Chlamydia induced Reiter's disease.

Synovial fluid (SF) mononuclear cells from a patient with Chlamydia trachomatis induced acute Reiter's disease were directly by limiting dilution in a representative protocol using phytohemagglutinin in the cloning medium. Out of 76 alpha beta-TCR+ CD4+ T lymphocyte clones, 7 were shown to specifically recognize C. trachomatis in a proliferation assay. The antigen recognition of these clones was HLA-DP restricted. Unexpectedly, 2 HLA-DR restricted clones showed a proliferative response to Yersinia enterocolitica O3, though the patient had no history of yersinia infection. The high frequency of SF derived T cells with specificity for species-specific chlamydial antigens and the limited diversity of HLA class II restriction of these clones may indicate an oligoclonal synovial T cell response to persistent intraarticular chlamydia.

Adult↗
PubMed1991

Synovial T lymphocyte-specific immune response to Chlamydia trachomatis in Reiter's disease.

We studied the lymphocyte proliferative response to Chlamydia trachomatis in Reiter's syndrome (RS) compared with that in other rheumatic diseases. RS patients showed significantly increased C trachomatis-specific synovial fluid (SF) T cell proliferation. Proliferating cells were found in both CD4+ and CD8+ T cell subsets. The SF lymphocyte proliferative response to C trachomatis in RS was inhibited by anti-class I and class II major histocompatibility complex monoclonal antibodies, while the response to tuberculin purified protein derivative was inhibited only by anti-class II monoclonal antibodies. T cell receptor gamma/delta-bearing T cells were not consistently increased in RS SF compared with peripheral blood, nor did such cells consistently expand upon in vitro culture with C trachomatis. Finally, there was no correlation between the cellular immune response and levels of antibody to C trachomatis antigens. Our results indicate that a specific T cell response to C trachomatis within the joint plays a role in the pathogenesis of RS.

Adult↗
PubMed1991

Visceral leishmaniasis mimicking a flare of systemic lupus erythematosus.

Fever in systemic lupus erythematosus (SLE) may be caused by exacerbation of the disease itself or by infection. We report on a patient with a long standing history of SLE that was complicated by fever and pancytopenia with no splenomegaly. SLE disease activity was suspected because of an elevated DNA-antibody titer. The early positive response to corticoid therapy may have masked the underlying infection. Visceral leishmaniasis was diagnosed by a repeated bone marrow biopsy and serological testing.

Animals↗
PubMed1990

[Dynamic magnetic resonance imaging in the differentiation of inflammatory joint lesions].

Eighteen patients with inflammatory lesions of the knee joints (ten with rheumatoid arthritis, eight with undiagnosed lesions) and two normal subjects were examined by MRI. In addition to spin-echo measurements, the signals from normal and pathological tissues were evaluated quantitatively by dynamic flash sequences following the injection of gadolinium DTPA. The latter method was able to distinguish active pannus from other proliferative synovial changes; the degree of activity could be related to synovial histology and relevant clinical features in eight patients. Areas of flat articular and subchondral pannus could be identified by the enhanced signal following the administration of gadolinium DTPA. Dynamic MRI is able to provide important information for the early diagnosis and follow-up of patients with rheumatoid arthritis.

Adolescent↗
PubMed1990

Rheumatoid arthritis: evaluation of hypervascular and fibrous pannus with dynamic MR imaging enhanced with Gd-DTPA.

The knees of 20 patients with rheumatoid arthritis and two healthy volunteers were evaluated with magnetic resonance (MR) imaging. Spin-echo sequences were performed, and the signal-intensity patterns of normal and pathologic articular soft-tissue structures were quantitatively evaluated with a dynamic FLASH (fast low-angle shot) sequence after bolus intravenous injection of gadolinium diethylenetriaminepentaacetic acid. In contrast to the spin-echo images obtained before injection of contrast material, it appears possible with this technique to distinguish joint effusion from hypervascular pannus formations and to grade the vascularity of proliferative synovitis. Flat pannus deposits on the articular surface and subchondral pannus masses were identified only by their marked enhancement of signal intensity after injection of contrast material. Dynamic MR imaging appears to yield decisive information for diagnosing rheumatoid arthritis.

Adult↗
PubMed1988

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

Adolescent↗
PubMed1978

[Interstitial pneumonia in children with acute lymphoblastic leukemia. prophylaxis with pentamidine during induction chemotherapy (author's transl)].

The influence of pentamidine prophylaxis on incidence and degree of interstitial pneumonia (IP) during a standardized induction chemotherapy in 100 children with acute lymphoblastic leukemia has been investigated. For radiologic evaluation we established three stages of IP. With pentamidine prophylaxis the incidence of IP was reduced from 48% to 9%. In addition, there was a significant reduction of severe or lethal courses.

Amidines↗
PubMedDate not supplied

Therapy of ankylosing spondylitis. Part II: biological therapies in the spondyloarthritides.

Therapeutic options for patients with active and severe spondylarthritis (SpA) have been fairly limited in the past decades. There is now accumulating evidence that biological therapy with agents directed against tumour necrosis factor-alpha (TNF-alpha) is highly efficacious in the spondyloarthritides, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The TNF blocking agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis (RA) in Europe and the USA. In contrast to rheumatoid arthritis (RA) disease-modifying anti-rheumatic drugs (DMARDs) have limited efficacy in SpA. No DMARDs are available for AS patients with active spinal disease. Thus, for AS patients whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs), therapy with TNF blockers may be considered as a first-line treatment. For infliximab, a dose of 3-5 mg/kg seems to be required, and intervals between 6 and 12 weeks are necessary to suppress disease activity continually. The standard dosage of etanercept is 2 x 25 mg subcutaneously (s.c.) per week. There are very few studies with adalimumab (standard dose in RA 20-40 mg s.c. every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. There is some evidence that both agents also work in other SpA, especially in PsA. Withdrawal of long-term therapy in AS patients led to relapses of disease after several months. Less radiographic progression after 2 years of continuous treatment with infliximab compared to conventional therapy has been suggested in a small study. Serious adverse events on anti-TNF therapy have remained rare. However, severe infections, including tuberculosis, have been reported. These can be largely prevented by appropriate screening. The benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Antirheumatic Agents↗