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Biomedical subjects

J Sieper

Publications and source records attributed to J Sieper.

At least 145 records · Page 8Linked to original sources
PubMed1998

Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors.

OBJECTIVE: To determine the overall prevalence of spondylarthropathy (SpA) among whites. METHODS: To screen for SpA symptoms, such as inflammatory back pain (IBP), joint swelling, psoriasis, and uveitis, or a specific family history, questionnaires were mailed to 348 blood donors (174 HLA-B27 positive and 174 HLA-B27 negative). From the responding 273 persons (78%; 140 B27 positive, 133 B27 negative), 126 were selected for further evaluation based on the symptoms reported. Of this group, 90 persons agreed to undergo physical examination (71.4%; 46 B27 positive, 44 B27 negative). There was no difference between the B27-positive and -negative groups in terms of age (mean +/- SD 38.4 +/- 10 versus 39.5 +/- 11 years) and sex ratio (67% versus 68% were men). In addition, 58 donors (32 B27 positive, 26 B27 negative) agreed to undergo magnetic resonance imaging (MRI) of the sacroiliac joints. A diagnosis of SpA and ankylosing spondylitis (AS) was made according to the European Spondylarthropathy Study Group criteria and the New York criteria. RESULTS: SpA was diagnosed in 20 persons: 19 of 140 B27-positive (13.6%) and 1 of 133 B27-negative (0.7%) subjects (15 male and 5 female). AS was diagnosed in 9 persons (7 male and 2 female; 45%), undifferentiated SpA (USpA) in 7 (5 male and 2 female; 35%), psoriatic arthritis (PsA) in 3 (2 male and 1 female; 15%), and chronic reactive arthritis (ReA; Reiter's syndrome) in 1 (male; 5%). On the basis of a B27 frequency of 9.3% among the population of Berlin (3.47 million persons), the estimated prevalence of SpA was 1.9%, AS was 0.86%, USpA was 0.67%, and PsA was 0.29%. The relative risk of developing SpA in B27-positive subjects was calculated as 20.7 (95% confidence interval 4.6-94.2; P = 0.001). Of 58 persons with IBP, sacroiliitis was detected by MRI in 15 of 32 B27-positive (46.9%) and 1 of 26 B27-negative (3.9%) subjects (P = 0.002). Four of these 16 donors did not fulfill diagnostic criteria for SpA. CONCLUSION: With a calculated prevalence of 1.9%, spondylarthropathies are among the most frequent rheumatic diseases in the white population. HLA-B27 positive persons carry a 20-fold increased risk of developing SpA. AS and USpA are the most frequent SpA subtypes. Persons with IBP who are B27 positive have a 50% likelihood of having sacroiliitis.

Adult↗
PubMed1998

Characterization of the synovial T cell response to various recombinant Yersinia antigens in Yersinia enterocolitica-triggered reactive arthritis. Heat-shock protein 60 drives a major immune response.

OBJECTIVE: In Yersinia enterocolitica-triggered reactive arthritis (Yersinia ReA), the synovial T cell response is primarily directed against bacterial components, which are mostly unknown. This study was performed to investigate the synovial proliferative T cell response to a panel of recombinant Yersinia antigens in patients with Yersinia ReA and in controls. METHODS: Synovial fluid mononuclear cells (SFMC) were obtained from 4 patients with Yersinia ReA and from 14 patients with arthritides of different etiology. SFMC were stimulated with 5 recombinant Yersinia antigens (the 19-kd urease beta subunit, 13-kd ribosomal L23 protein, 32-kd ribosomal L2 protein, 18-kd outer membrane protein H, and Y. enterocolitica heat-shock protein 60 [hsp60]), and with human, Chlamydia trachomatis, and Borrelia burgdorferi hsp60. Three T cell clones specific for Y. enterocolitica hsp60 were generated from 1 patient with Yersinia ReA. Antigen-induced cytokine release was measured by enzyme-linked immunosorbent assay. RESULTS: SFMC from all 4 patients with Yersinia ReA responded to each of the Yersinia antigens except the 13-kd protein. These antigens were also recognized by SFMC from a subgroup of patients with undifferentiated arthritis (n = 4), but not by SFMC from other patients with arthritis of different etiology (n = 10). Y. enterocolitica hsp60 induced the strongest proliferative response in all cases. Two types of hsp60-reactive T cell clones could be obtained. One clone responded to all hsp60 variants, including the human variant, and showed a type 2 T helper (Th2)-like cytokine-secretion pattern. In contrast, another clone with specificity for the bacterial hsp60 proteins, but not the human equivalent, reacted with a more Th1-like pattern. CONCLUSION: In Y. enterocolitica-triggered ReA, at least 4 immunodominant T cell antigens exist, which might be used in lymphocyte proliferation assays to identify patients with Yersinia ReA. The hsp60 is a strong antigen, inducing both bacteria-specific and potentially autoreactive CD4+ T cells of both the Th1 and Th2 type.

Adolescent↗
PubMed1998

Lack of correlation between the detection of Chlamydia trachomatis DNA in synovial fluid from patients with a range of rheumatic diseases and the presence of an antichlamydial immune response.

OBJECTIVE: To resolve how frequently Chlamydia trachomatis and Chlamydia pneumoniae DNA are present in the joints of unselected patients with reactive arthritis (ReA) and undifferentiated oligoarthritis, and to determine if there is an accompanying serologic or cellular antichlamydial immune response. METHODS: Two polymerase chain reaction (PCR) protocols to detect the plasmid of C. trachomatis and the outer membrane protein 1 gene of C. pneumoniae were developed for specific use with synovial fluid (SF). Subsequently, the assays were used to detect DNA from the 2 organisms in SF from 54 adult patients with rheumatic diseases, including 4 with sexually acquired ReA and 31 with undifferentiated oligoarthritis. The presence of chlamydial antibodies and SF lymphocyte proliferation responses were determined in parallel. RESULTS: The PCR protocols were species-specific and highly sensitive. SF samples from 15 patients (8 with undifferentiated oligoarthritis, 3 with ReA, 1 with rheumatoid arthritis, and 1 with psoriatic arthritis) were positive for C. trachomatis. There was no significant correlation between the presence of C. trachomatis DNA in the joint and a Chlamydia-specific synovial T cell response or a serologic response. C. pneumoniae was not detected in any of the 54 patients, although it was identified in the SF from a rheumatoid arthritis patient outside this study, demonstrating that the assay was capable of detecting the organism in the joint. CONCLUSION: C. trachomatis DNA was present in ReA patients and in nearly one-third of unselected patients with undifferentiated oligoarthritis, which further supports the hypothesis that it plays an important role in disease pathogenesis. However, its presence did not correlate with evidence of an antichlamydial immune response. Despite previous anecdotal reports, C. pneumoniae does not appear to be a major cause of undifferentiated oligoarthritis or ReA.

Adult↗
PubMed1998

Overexpanded B cell clone mediating leukemic arthritis by abundant secretion of interleukin-1beta: a case report.

The role of cytokines in leukemic arthritis is unknown. The presentation of a patient with B cell chronic lymphocytic leukemia and destructive arthritis of the wrist joints prompted us to study the synovial cytokine pattern by immunohistologic analysis. In addition, rearranged V(H) and V(L) immunoglobulin genes were sequenced to assess B cell clonality. Heavy infiltrations of CD20+ cells with lambda light chain restriction were found in the synovial tissue. Sequencing demonstrated overexpansion of a single B cell clone (DP58/D/J(H)4b and IGLV3S2/Jlambda2-Jlambda3 for V(H) and V(L), respectively) in the peripheral blood. Identical V(H) and V(L) rearrangements were found in the synovial infiltrates. Somatic mutations were found in both the peripheral blood and the synovial clone. Immunohistologic study revealed the presence of abundant interleukin-1beta (IL-1beta) and, to a lesser degree, tumor necrosis factor beta (TNFbeta) (lymphotoxin). In contrast, TNFalpha, interferon-gamma, IL-4, IL-6, and IL-10 were rarely found in the synovial infiltrates. Therefore, IL-1beta secreted in great amounts by leukemic B cells appears to be the major cytokine that mediates joint destruction in leukemic arthritis.

Amino Acid Sequence↗
PubMed1998

Modulating the Th1/Th2 balance in inflammatory arthritis.

The balance between Th1 and Th2 cells regulates the choice between inflammatory and antibody-mediated immune responses. To an increasing extent this balance is thought to involve the participation of antigen-presenting cells, rather than the entirely autonomous activity of T cells and their cytokines. Here we survey current opinion concerning the working of this balance, and its condition in rheumatoid arthritis and the other inflammatory arthritides. The contrast between Lyme arthritis and reactive arthritis is particularly illuminating, since one is triggered by extracellular and the other by intracellular infection. We describe current approaches to the modulation of this balance. Guided by the principles that genetic polymorphism is likely to identify relevant genes, that any cytokine gene picked up by a virus must matter and that natural immunosuppressive activity at mucosal surfaces should be worth exploiting, we identify as particularly worthy of attention: (i) IL-10, (ii) inhibitors of IL-12 production, (iii) inhibitors of CD40 ligand expression and (iv) oral and nasal tolerance. Other protective T cell subsets are touched on, and the impact of oligonucleotide arrays mentioned.

Animals↗
PubMed1998

Radiologic diagnosis and pathology of the spondyloarthropathies.

Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by conventional radiography and even better by computed tomography--especially when bony changes have already taken place. The advantage of dynamic magnetic resonance imaging (MRI) is to visualize morphologic changes and inflammation at the same time. This facilitates detection of sacroiliitis and spondylitis/spondylodiscitis at early time points. Hopefully, this will lead to other forms of therapy to prevent ankylosis of the spine. The origin of the granulation tissue infiltrating cartilage and bone in AS might be the synovium, the subchondrium or the bone marrow itself. T cells and macrophages seem to play an important role in this inflammatory process in which TNF-alpha is present in severe cases. The mechanisms responsible for the increased bone formation observed in the course of AS are unknown.

Animals↗
PubMed1998

Bacteria-specific lymphocyte proliferation in peripheral blood in reactive arthritis and related diseases.

The cellular immune response seems to be important for the pathogenesis of reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is often found in synovial fluid (SF) of ReA patients. However, the role of the bacteria-specific LP in peripheral blood (PB) is less well defined. In this study, we investigated 215 paired samples of SF and PB from patients with ReA (n = 65), undifferentiated oligoarthritis (n = 133) and undifferentiated spondylarthropathy (n = 17) to analyse the LP in PB and SF in relation to time. In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a positive LP to the same bacterium was also found in PB. While a positive LP in SF was found most frequently in the first week of the arthritis, a positive LP in PB was detected in 45% of patients when investigated between weeks 2 and 4 after the onset of arthritis, but was rarely found very early and late in the course of the arthritis. The time point seems to be crucial for the investigation of an LP in PB in patients with ReA.

Adolescent↗
PubMed1998

Longitudinal investigation of bacterium-specific synovial lymphocyte proliferation in reactive arthritis and lyme arthritis.

BACKGROUND: Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients. METHODS: In this study, the synovial lymphocyte proliferation to Yersinia, Chlamydia, Shigella and Borrelia burgdorferi was investigated sequentially at different time points in 28 patients with reactive arthritis, undifferentiated oligoarthritis or Lyme arthritis responding to one of these bacteria. RESULTS: The same bacterium was always recognized in arthritis triggered by Chlamydia, Shigella or Borrelia, with much variation in the proliferative response. Only the Yersinia-specific responses changed specificity, suggesting that the proliferative response to Yersinia is non-specific in some patients. CONCLUSIONS: Our data support the concept of a local antigen-specific T-cell response in reactive arthritis or Lyme arthritis but not the concept suggested by others that a switch to an autoimmune response takes place in long-standing disease.

Antigens, Bacterial↗
PubMed1998

Use of dynamic magnetic resonance imaging to detect sacroiliitis in HLA-B27 positive and negative children with juvenile arthritides.

OBJECTIVE: Involvement of the sacroiliac (SI) joints is a hallmark of the spondyloarthropathies (SpA), especially, in early and later stages of ankylosing spondylitis in adults. The significance of sacroiliitis in juvenile SpA is less clear and the diagnosis of juvenile SpA is difficult due to the mostly nonspecific or absent history of back pain in children and the time delay associated with the diagnosis of sacroiliitis by conventional radiographs. Our aim was to evaluate dynamic magnetic resonance imaging (MRI) of the SI joints in children and to assess the frequency and the determinants of SI joint involvement in juvenile SpA and other juvenile arthritides. METHODS: Clinical examinations and dynamic MRI were performed in 130 children < 16 years of age with joint complaints, 100 with probable SpA, and 30 controls. The degree of back pain was assessed by a visual analog scale (VAS) (0 = no pain, 10 = very severe pain). The following groups were defined before MRI investigation according to modified European Spondylarthropathy Study Group (ESSG) criteria for SpA: Group 1: undifferentiated SpA (uSpA, n = 41, 88% B27+); Group 2: differentiated SpA (n = 29, 97% B27+), comprising reactive arthritis (n = 16), ankylosing spondylitis (n = 9), psoriatic arthritis (n = 3), and arthritis in inflammatory bowel disease (n = 1); Group 3: patients with no signs of SpA other than oligoarthritis, here named juvenile chronic arthritis (JCA) II (n = 30, 93% B27+); Group 4: HLA-B27+ controls without arthritis (n = 12); and Group 5: HLA-B27-controls with various other non-SpA diagnoses (n = 18). MRI was evaluated according to published criteria allowing for differentiation between acute and chronic changes in SI joints. RESULTS: Acute sacroiliitis without chronic changes could only be detected by dynamic MRI: in 17 patients (11 in Group 1, 3 in Group 2, 3 in Group 3) together in 14/70 (20%) patients with SpA. All these 17 patients had normal pelvic radiographs. Using MRI acute and/or chronic sacroiliitis were found in 35 patients: 17/41 in Group 1 (41%), 15/29 in Group 2 (52%), and 3/30 (10%) patients in Group 3, but in no patients in Groups 4 and 5. Chronic SI joint changes > grade 1 were detected by MRI in 18/70 patients with SpA (25.7%). In comparison, radiographic changes > grade 1 were less often detected in 14/70 patients with SpA (20%) or 23/210 SI joints examined (11 %), compared to 29/210 SI joints found in the MRI examinations (14%) (p = 0.05). Among the 70 patients with SpA, those with MRI diagnosis of acute sacroiliitis had a significantly longer disease duration (62+/-34 vs 28+/-16 months; p = 0.01) and higher C-reactive protein (12+/-12 vs 9+/-14; p = 0.01), and also reported more back pain on VAS (4.3+/-3.6 vs 1.2+/-2.2; p = 0.001) than those without sacroiliitis. CONCLUSION: Dynamic MRI and MRI are useful to detect acute and chronic sacroiliitis in children. The main advantages in comparison with conventional radiographs are the ability to detect acute changes in the SI joints, the higher sensitivity to detect chronic changes, and clearly, the lack of radiation exposure; while the disadvantages are the high costs and the duration of the procedure. Sacroiliitis is fairly common in juvenile SpA and seems to be associated with disease intensity and duration.

Adolescent↗
PubMed1998

Increased frequency of Sjögren's syndrome in patients with spondyloarthropathy.

OBJECTIVE: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). METHODS: Patients with SpA with inflammatory back pain and/or peripheral arthritis presenting to the university outpatient clinic were diagnosed as AS (n = 40) and uSpA (n = 65) according to established criteria. Patients with SpA with sicca symptoms and/or positive antinuclear antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or sialography. To assess sicca symptoms in this cohort systematically we mailed a validated questionnaire with 6 questions on dryness of eyes and mouth to all 105 SpA patients and 150 healthy controls, a positive answer to > or = 3 questions was taken as suggestive of SS. There was no significant difference in baseline characteristics between patients and controls. RESULTS: In 8/105 SpA patients (5 uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS; thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients responding to the questionnaire (80%), 10 gave a positive answer to > or = 3 questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7, 95% CI 2.3-32.5, p < 0.01). CONCLUSION: The data suggest increased prevalence of sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a secondary SS in a variety of inflammatory diseases suggests that salivary gland involvement in these conditions results from as yet unidentified shared pathogenic mechanisms resulting in nonspecific inflammation in this location.

Adult↗
PubMed1997

A single nonamer from the Yersinia 60-kDa heat shock protein is the target of HLA-B27-restricted CTL response in Yersinia-induced reactive arthritis.

The reason for the high association of HLA-B27 with diseases such as ankylosing spondylitis and reactive arthritis is not clear. In reactive arthritis, the triggering bacteria are known, thus allowing investigation of their interaction with HLA-B27. CTL lines derived from five patients with Yersinia-induced reactive arthritis were raised by repeated stimulation in vitro with either Yersinia-infected autologous macrophages (four patients) or pooled peptides (three patients) having the HLA-B27-binding motif. The peptides were derived from five Yersinia proteins and from the chlamydial 57-kDa heat shock protein (hsp). Cytotoxicity of T cell lines was then tested against these peptides. Lytic activity was obtained with T cells stimulated with viable Yersinia or pooled peptides. Targets successfully used for lysis were cells pulsed with peptides from the Yersinia 60-kDa hsp, but not cells pulsed with peptides from other Yersinia proteins or the chlamydial hsp. T cell lines raised with 60-kDa peptides also lysed targets infected with Yersinia. Most interestingly, all three CTL lines tested (one raised with Yersinia; two with pool of peptides) recognized only one single peptide (321-329) of seven tested from the Yersinia hsp60. Cytotoxicity occurred only when target cells were matched for HLA-B27. This identification of an immunogenic peptide derived from an arthritogenic bacterium and presented by HLA-B27 opens the way for future investigation of the role of T cells specific for this peptide or cross-reacting peptides, in the immunopathology of HLA-B27-associated diseases.

Arthritis, Infectious↗
PubMed1997

[Costosternal swelling and diffuse bone pain in tubercular osteomyelitis].

HISTORY AND CLINICAL FINDINGS: For about a year a 28-year-old Nigerian had been suffering from diffuse bone pain, intermittent fever, weight loss and weakness. Physical examination was unremarkable except for a swelling at the sternal angle. INVESTIGATIONS: The tuberculin test was clearly positive and tests for inflammatory disease were elevated, but the chest radiograph was normal. Bone scintigraphy demonstrated multiple sites of increased storage in the ribs and vertebral column. Magnetic resonance imaging revealed a large paravertebral abscess, which was needled under computed tomography monitoring. Polymerase chain reaction of the aspirate demonstrated Mycobacterium tuberculosis. TREATMENT AND COURSE: While initial treatment with combined isoniazid, streptomycin, rifampicin and pyrazinamide, the first two drugs had to be discontinued, the microorganism not being sensitive to them, and were replaced by ethambutol and amikacin. The abscess was drained and the vertebral fracture surgically stabilised. There were no neurological abnormalities and the lesions largely healed. CONCLUSION: Even without pulmonary involvement tuberculosis must be included in the differential diagnosis of rheumatic diseases with joint and vertebral column involvement, such as the SAPHO syndrome and other inflammatory bone diseases.

Abscess↗
PubMed1997

T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines.

OBJECTIVE: To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines. METHODS: The cytokine pattern in the joints of 10 patients with Lyme arthritis was investigated. Expression of interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptase-polymerase chain reaction and immunohistologic techniques. The effects of recombinant cytokines or neutralizing anticytokine antibodies on cytokine production in Bb-stimulated SFMC were investigated by ELISA. RESULTS: SFMC produced high amounts of IFN gamma and TNF alpha, but little or no IL-4, upon stimulation with Bb antigen, indicating a Th1-type cytokine pattern. In SM, IFN gamma was detectable in all patients, while the other cytokines were less frequently found. Serial sections of SM revealed that all cytokines were located in the same area. The Th1 response, especially the production of TNF alpha, could be down-regulated in vitro by both endogenous and exogenous IL-10, but not by IL-4 or anti-IL-12. CONCLUSION: A Th1-type cytokine pattern was found in the joints of patients with Lyme arthritis. This Th1 response could be down-regulated by IL-10, suggesting insufficient IL-10 production in vivo.

Adolescent↗