[Cytokine expression in coxarthrosis and knee osteoarthritis].
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Cartilage, Articular↗
Biomedical subjects
J Sieper
Publications and source records attributed to J Sieper.
Sweet's syndrome in a patient with acute Crohn's colitis and longstanding ankylosing spondylitis.
Acute neutrophilic dermatosis, also referred to as Sweet's syndrome according to the first description in 1964, occurs not only as an isolated phenomenon but also in the context of neoplastic and inflammatory diseases, occasionally including arthritides. Recently Sweet's syndrome has been reported in a small number of patients with chronic inflammatory bowel disease, mostly in advanced stages of the disease. Here, we describe the sudden outbreak of acute neutrophilic dermatosis in coincidence with the onset of severe Crohn's disease (CD) in a patient with long-standing ankylosing spondylitis (AS). This condition has not been described before and therefore Sweet's syndrome should be added to the spectrum of skin manifestations the rheumatologist has to think about in the context of the spondylarthropathies (SpA). Furthermore, this case report is of interest because the skin lesions of Sweet's syndrome are somewhat similar to psoriasis, which is a rather frequent feature of the spondylarthropathies. This article intends to clarify the clinical and histological differentiation between Sweet's syndrome, psoriatic skin lesions and erythema nodosum for the rheumatologist and stresses that these conditions must each be treated in a completely different manner.
Acute Disease↗
Co-occurrence of spondyloarthropathy and connective tissue disease: development of Sjögren's syndrome and mixed connective tissue disease (MCTD) in a patient with ankylosing spondylitis.
Spondylarthropathies (SpA) and connective tissue diseases (CTD) are clinically distinct entities which, at first glance, seem to have little in common. However, a link between SpA and CTD has recently been suggested by a study in which a higher prevalence of Sjögren's syndrome (SS) and sicca symptoms was reported in patients with ankylosing spondylitis (AS) and undifferentiated SpA (1). Another link between SpA and CTD is a possible side effect of a DMARD widely used to treat SpA: sulfasalazine (SAS). SAS was reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus. This report describes a 54-year-old white male, HLA B27-positive AS patient with some syndesmophytes who, after 15 years of disease, developed SS with salivary gland involvement, Raynaud's syndrome and anti-Ro antibodies. Then, 20 years after the onset of AS, he became acutely ill, suffering severe myositis and myocarditis along with swollen hands and highly elevated autoantibody titers recognizing UIRNP; his condition was interpreted as mixed connective tissue disease (MCTD). The patient had been treated with SAS and azathioprine (AZA) alone several times during the last years because he had not tolerated other DMARDs. A combination of both drugs had been prescribed 3 weeks before a severe flair because of progredient high disease activity with painful peripheral arthritis of the MCP and PIP joints which, however, had not shown radiographic erosions. We describe the rare development of MCTD in an AS patient and report, for the first time, the onset of MCTD potentially triggered by sulfasalazine.
Humans↗
Immunological basis for the use of TNFalpha-blocking agents in ankylosing spondylitis and immunological changes during treatment.
TNFalpha is expressed in high amounts at the site of inflammation in ankylosing spondylitis, which provided the basis to initiate treatment studies with TNF-blocking agents. We could show that the immunological effects of infliximab and etanercept differ in patients with AS, although the clinical effect was similarly good. While infliximab induced a downregulation of the production of the T-helper 1-cytokines IFNgamma and TNFalpha, etanercept treatment triggered rather an upregulation of these cytokines secreted by T cells after in vitro stimulation.
Antibodies, Monoclonal↗
Infliximab in the treatment of active and severe ankylosing spondylitis.
For treatment of the spondylarthropathies (SpA), of which ankylosing spondylitis (AS) is the prototype, there is no effective disease modifying treatment available. In contrast to rheumatoid arthritis (RA), few studies have been performed on the treatment of patients with AS with disease modifying antirheumatic drugs, none of which have proved clearly effective in axial disease. Many patients with AS carry a heavy burden of disease and AS itself is responsible for direct and indirect socioeconomic costs. To find an effective treatment for severe ankylosing spondylitis is therefore thought to be an unmet medical need. In the last four years several pilot studies and recently a few randomised controlled trials have raised good evidence that TNFalpha blockade is very effective in AS and other SpA. Disease activity, function and quality of life improved upon treatment with TNFalpha blockers. Thus, biologicals seem to represent a major breakthrough in the treatment of AS and other SpA. Side effects similar to those observed in RA treatment occur. But there is furthermore a need for safety data for long-term treatment with biologicals over several years. In the light of the high costs and the unknown long-term side effects, a definition for patients who might be candidates for such a treatment is needed. This article gives detailed information about current experience with the new treatment options in active and severe AS with anti-TNFalpha therapy.
Antibodies, Monoclonal↗
Use of contrast enhanced magnetic resonance imaging to detect spinal inflammation in patients with spondyloarthritides.
Inflammation of spinal structures is a characteristic feature of the spondyloarthritides (SpA). The term SpA covers patients with inflammatory back pain and/or peripheral arthritis who can be further categorized. Ankylosing spondylitis (AS), the prototype of the SpA, the most frequent inflammatory spinal disease in adults, usually starts in the sacroiliac joints. Pathologic spinal changes occurring in AS are spondylitis, spondylodiscitis and inflammation and ankylosis also at other sites in the axial skeleton. In the later stages of AS such changes can be well recognized by spinal x-rays. In the early disease stages it has been more difficult to analyze the exact anatomic localization of spinal inflammation to date, because conventional imaging systems have only a limited capacity to demonstrate such changes early. There is some evidence that magnetic resonance imaging (MRI) with fat saturation and contrast enhanced MRI are useful to visualize early and late inflammatory changes in the sacroiliac joints. In this paper we report that MRI is also useful to localize the site of inflammation to distinct regions of the spine in AS and other SpA.
Adult↗
Imaging and scoring in ankylosing spondylitis.
Ankylosing spondylitis (AS), the prototype of the spondyloarthritides (SpA), is a disease subset but also a possible outcome of the SpA. Early diagnosis of sacroiliitis, the most frequent clinical symptom often accompanied by inflammatory back pain, and other inflammatory lesions of the spine such as spondylitis and spondylodiscitis, can be visualized early by magnetic resonance imaging (MRI). Chronic changes such as syndesmophytes are well detected by conventional x-rays of the spine, mostly lateral, in the lumbar spine also a.p. Active spinal inflammation can be demonstrated by MRI by using either the fat saturating STIR technique or by application of the contrast agent gadolinium-DTPA. This is especially useful in early and active disease, in young women and in children, and for the differential diagnosis of septic sacroilitis. Because of the efficacy of the novel biologic agents directed against TNFalpha such as infliximab and etanercept in SpA there is a need for spinal imaging techniques that are more sensitive than conventional x-rays. The available scoring tools are limited in their sensitivity to change. Novel approaches using MRI have been recently proposed.
Disease Progression↗
Anti-TNF therapy and the spondyloarthritides: who should be treated?
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Humans↗
CD27+ memory and CD27- effector CD8+ T cells are responsible for a decreased production of proinflammatory cytokines in HLA B27-positive subjects.
BACKGROUND AND OBJECTIVE: AS and other spondyloarthritides (SpA) are mostly chronic inflammatory rheumatic diseases characterised by a strong association with HLA B27. Recent data from our group have suggested that AS patients have a diminished secretion capacity of inflammatory cytokines, possibly associated with HLA B27. The aim of this study was to identify CD4+ and CD8+ T cell subsets responsible for the observed lower cytokine secretion capacity in HLA B27-positives. METHODS: Highly purified (> 98%) CD4+ and CD8+ T cells of HLA B27-positive AS patients (n = 13), healthy HLA B27-positive (n = 7) and -negative controls (n = 9) were stimulated for 6h with PMA/ Ionomycin and, after fixation, stained for surface markers CD45RA and CD27 and cytokines TNFalpha, IFNgamma, IL-4 and IL-10. RESULTS: CD27+ CD45RA- memory CD8+ T cells of HLA B27-positive subjects showed a significantly lower percentage of TNFalpha (median 71.4%) and IFNgamma production (median 69.7%) than HLA B27-negative controls (TNFalpha 85.1%; p < or = 0.027; IFNgamma 82.7%, p < or = 0.026). A similar result was also detected in CD27- CD45RA+ effector CD8+ T cells of which 43.2% produced TNFalpha and 66.3% IFNgamma in HLA B27-positive subjects, respectively, compared to 75.6% TNFalpha and 84.4% IFNgamma producing T cells in HLA B27-negatives (p < or = 0.045 and p < or = 0.062, respectively). For all CD4+ T cell subsets no significant differences between HLA B27-positive and HLA B27-negative donors were observed, regarding neither the frequency of IFNgamma, TNFalpha, IL-4 or IL-10 producers nor the coexpression of IFNgamma and IL-4 in memory subsets. CONCLUSIONS: HLA B27-positive subjects are characterized by a low proinflammatory cytokine production in CD8+ effector and memory T cell subsets. This suggests an influence of HLA B27 on cytokine production in antigen-experienced CD8+ T cells.
Adult↗
[Rheumatologic patient management and research in Berlin at the intersection between East and West].
After the fall of the Berlin Wall in November 1989, there was an immediate need for collaboration between rheumatologists from East- and West-Berlin from the very beginning, which could be taken as an example for the rest of Germany. This was achieved through different activities in patient care and research. The "Regionales Rheumazentrum Berlin" which was started at about that time played a special role in making this enterprise a success.
Berlin↗
Immunological basis of oral tolerance.
Oral tolerance may be defined as a specific reduction in the immune response brought about by feeding an antigen. It has been reviewed by us recently as a possible treatment of rheumatoid arthritis. It has a respectably long history as an experimental phenomenon, in the course of which a variety of modes of action have been proposed. More recently the following mode of action has been proposed: An antigen, for instance foreign type II collagen, passes from the lumen of the gut across multifold-cells (M-cells) lying under Peyer's patches, and thence into antigen-presenting cells within the patches. These cells then activate a local population of T cells which specializes in the secretion of transforming growth factor-beta (TGF beta) and IL-4. Following activation a few of these cells wander out through the lymphatics and blood stream, and thence through tissue, until they again find type II collagen, their recall antigen. What they find in a patient with inflammatory arthritis, it is believed, is self-type II collagen exposed within the inflamed joints, which they recognize via its cross-reaction with the foreign collagen which had originally activated them. The specialized T cells are then stimulated by their recall antigen to secrete TGF beta and IL-4. These inhibitory cytokines suppress the activity of neighboring disease-inducing Th1 cells ("bystander suppression"). The latter cells presumably recognize one or more autoantigens, the nature of which is unknown. It need not be type II collagen, which figures in the whole story only as an organ-specific antigen, which lures the suppressive T cells to the right place.
Administration, Oral↗
[Reactive arthritis associated bacteria as the etiology of undifferentiated oligoarthritis].
Undifferentiated oligoarthritis (UOA) resembles clinically reactive arthritis (ReA), but does not fulfill the diagnostic criteria. In 46 patients with UOA, in 16 with ReA, and in 15 with rheumatoid arthritis (RA) the humoral and cellular immune response to the ReA-associated bacteria Chlamydia trachomatis, Yersinia enterocolitica, Shigella flexneri, Salmonella enteritidis, Campylobacter jejuni and Borrelia burgdorferi was investigated in paired samples of synovial fluid and peripheral blood. An antigen-specific lymphocyte proliferation in SF was found in 75% of the ReA and in 39% of UOA patients, but in none with RA. Shigella and Chlamydia in ReA and Yersinia and Chlamydia in UOA were the most frequent stimulating antigens. There was a poor correlation between antigen specific lymphocyte proliferation and specific antibodies. We conclude that these bacteria might have a pathogenetic role, not only in ReA, but also in UOA.
Adult↗
[Synovial cellular immune response to bacterial pathogens in patients with chronic juvenile arthritis].
Juvenile chronic arthritis is a heterogenous disease with an ill-defined pathogenesis. In our study, synovial fluid (SF) and peripheral blood (PB) of 70 children with oligoarthritis were investigated; bacteria-specific lymphocyte proliferation and antibodies to arthritogenic bacteria were determined. Specific cellular immune responses in SF but not in PB were found in 4/7 patients with either Lyme- or reactive arthritis (60%). In comparison, in subgroup JCA II (n = 45) encompassing mainly elder HLA B27 positive boys, a specific response in SF but again not in PB was detected in 10 children to Yersinia enterocolitica (YE), in four children either to Borrelia burgdorferi (BB) and Chlamydia trachomatis (CT), and in one child to Campylobacter jejuni (CJ). In contrast, in subgroup JCA I (n = 17) encompassing mainly young ANA-positive girls with chronic iridocyclitis, no specific response was found. The correlation of the synovial cellular and the humoral immune responses was 100% in the case of BB and 50% for YE; no antibodies against CT or CJ were detectable. Neither specific cellular nor humoral immune responses were detected against Salmonella or Shigella. We conclude that, in the pathogenesis of some patients with JCA, bacterial microbes have a triggering role. Mainly YE, but also BB and CT are responsible for cases of JCA in which no symptomatic infection preceded.
Adolescent↗
[Therapy with oral type II collagen as a new possibility of selective immunosuppression in therapy of rheumatoid arthritis].
Suppressor T cells in the mucosa of the gut are activated by absorbed antigen in order to avoid a systemic immune response to this antigen. This long known phenomenon of oral tolerance is now used in the treatment of rheumatoid arthritis with oral collagen type II which is the most important protein of cartilage. Although the role of collagen II in initiating and maintaining the immune response in the joint is not clear, these suppressor CD8+T cells can be stimulated in a trigger-specific and effector-nonspecific way by contact with collagen II in the joint. It is assumed that a local immunosuppression then takes place through the secretion of inhibitory cytokines, mainly TGF beta. Clinical studies in the treatment of rheumatoid arthritis are presently being conducted in Boston and Berlin.
Administration, Oral↗
Three-colour flowcytometric examination of CD4/CD45 subsets reveals no differences in peripheral blood and synovial fluid between patients with reactive arthritis and rheumatoid arthritis.
Reactive arthritis (ReA) and rheumatoid arthritis (RA) are inflammatory joint diseases which differ in several clinical and immunological aspects. In both diseases locally activated T cells are considered important for pathogenesis. Subsets of T cells are demonstrated by staining with monoclonal antibodies recognizing isotypes of the common leukocyte antigen: CD45RA, which is considered to be a marker of native T cells, and CD45RO a marker of primed T cells; a third subset was also identified according to the staining intensity of CD45RB: CD45RBbright and CD45RBdim. The expression of these and the surface markers CD3, CD4, CD8, CD14 and CD56 was studied in synovial fluid (SF) and peripheral blood (PB) of patients with ReA (n = 11), RA (n = 10) and normal controls (n = 10) by three-colour immunocytometry. Significantly more CD45RBbright were found in the PB of patients with ReA (64.1%) and RA (63.5%) than in the SF of ReA (36.8%) and RA (40.6%) patients. However, when analyzed in relation to CD45RO, the CD45RO/CD45RBbright population was not significantly different between the SF and PB of patients with ReA (32.2% vs. 26.8%) and RA (30.6% vs. 28.1%), respectively. Among the three cellular subtypes of CD4+ lymphocytes demonstrated in this study (CD45RA/RBbright, CD45RO/CD45RBbright and CD45RO/CD45RBdim) none, in contrast to previous results of other groups, showed marked differences between ReA and RA in either of the compartments examined.
Adolescent↗
Second International Workshop on Reactive Arthritis.
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Arthritis, Reactive↗