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M Rudwaleit

Publications and source records attributed to M Rudwaleit.

68 records · Page 4Linked to original sources
PubMed1999

Low secretion of tumor necrosis factor alpha, but no other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis.

OBJECTIVE: To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). METHODS: Secretion of tumor necrosis factor alpha (TNFalpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescence-activated cell sorting (FACS) was performed in 12 ReA patients and 12 RA patients. In 27 ReA patients, cytokine secretion was measured again after 3 months. Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. RESULTS: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNFalpha secretion in those with a disease duration of > or = 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04). CONCLUSION: Low TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.

Adult↗
PubMed1999

Studying patients with inflammatory back pain and arthritis of the lower limbs clinically and by magnetic resonance imaging: many, but not all patients with sacroiliitis have spondyloarthropathy.

OBJECTIVE: Clinical and magnetic resonance imaging (MRI) data of 170 consecutive patients with inflammatory back pain (IBP) and/or oligoarthritis of the lower limbs were evaluated in a retrospective study. The aim was to determine the frequency of sacroiliitis and spondyloarthropathy (SpA) in this population, and to assess the significance of HLA B27 measurements for diagnosis in early disease. METHODS: Pelvic X-rays were performed in all IBP patients and dynamic MRI of the sacroiliac joints in patients with IBP who had indefinite results on sacroiliac X-rays (n = 32). RESULTS: European Spondyloarthropathy Study Group criteria for SpA were fulfilled by 106/170 patients (62.4%); eight additional patients had symptoms suggestive of SpA (4.7%). The most frequent SpA subset was undifferentiated SpA (uSpA), diagnosed in 46/106 patients (43.4%). Sacroiliitis was detected by MRI in 21/32 patients with IBP and unclear X-rays (65.6%). Of those, 14 were diagnosed as SpA and seven females with moderate unilateral sacroiliitis, but no features of SpA, also not on follow-up (at least 1 yr), were classified as undifferentiated sacroiliitis (US). Ten of the 14 SpA (71.4%) and none of the seven US patients were HLA B27 positive. CONCLUSION: HLA B27 positivity in IBP patients with MRI-proven sacroiliitis positively predicts SpA. uSpA is a frequent SpA subset. There are HLA B27-negative non-SpA patients with moderate unilateral sacroiliitis whom we propose to be classified as US.

Adult↗
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

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

The role of germline polymorphisms in the T-cell receptor in susceptibility to ankylosing spondylitis.

The role of germline polymorphisms of the T-cell receptor A/D and B loci in susceptibility to ankylosing spondylitis was investigated by linkage studies using microsatellite markers in 215 affected sibling pairs. The presence of a significant susceptibility gene (lambda > or = 1.6) at the TCRA/D locus was excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family studies will be required to determine whether this is a true or false-positive finding. It is unlikely that either the TCRA/D or TCRB loci contain genes responsible for more than a moderate proportion of the non-MHC genetic susceptibility to ankylosing spondylitis.

Family Health↗
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↗
PubMed1996

Severe calciphylaxis in a renal patient on long-term oral anticoagulant therapy.

The pathogenesis of calciphylaxis, a potentially life-threatening condition, is not well understood. Several factors such as end-stage renal disease (azotemia), hyperparathyroidism, hyperphosphatemia, hypercalcemia, a high calcium-phosphate product, and the use of steroids and cytotoxic drugs after kidney transplantation are believed to interact in calciphylaxis. Recently, hypercoagulability due to functional protein C deficiency has been suggested to play a pathogenic role in this condition. Here, we present a renal transplant patient, with secondary hyperparathyroidism and on long-term oral anticoagulant therapy, who developed calciphylaxis with severe skin necrosis of her legs. The patient's condition improved dramatically after total parathyroidectomy. Hypercoagulability, therefore, does not appear to have played a significant role in this case of calciphylaxis.

Administration, Oral↗
PubMed1996

Interethnic differences in the association of tumor necrosis factor promoter polymorphisms with systemic lupus erythematosus.

OBJECTIVE: To assess the role of polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene in susceptibility to systemic lupus erythematosus (SLE). METHODS: Two ethnically different populations of patients with SLE (49 white from the UK and 49 black from South Africa) were genotyped for TNF-238 and TNF-308 polymorphisms using amplification refractory mutation system-polymerase chain reaction (PCR). HLA-DR genotypes were assigned to the patients and controls either serologically or by PCR and sequence specific oligonucleotides. The frequencies of the respective variants were compared between patients and ethnically matched controls. RESULTS: No significant differences were found in the frequency of the TNF-238 variants in either ethnic group. At TNF-308, the TNF2 variant was significantly increased (p = 0.04) in white patients with SLE compared to controls. However, TNF2 was strongly associated with HLA-DR3 (p = 0.00002), which also showed a strong trend of increase in the white patients (p = 0.06). In contrast, in the black patients with SLE in whom DR2 but not DR3 was increased, the frequency of TNF2 was actually reduced rather than increased. CONCLUSIONS: The increase of TNF2 in Caucasians with SLE is most likely due to linkage disequilibrium between TNF2 and DR3. Furthermore, the observation that TNF2 seems to be reduced in blacks with SLE strongly suggests this polymorphism is not an independent risk factor for SLE. Overall, our data indicate that the TNF-238 and TNF-308 promoter polymorphisms do not confer susceptibility to SLE.

Base Sequence↗
PubMed1995

HLA class II antigens associated with systemic lupus erythematosus in black South Africans.

OBJECTIVE: To assess the associations of HLA class II antigens with systemic lupus erythematosus (SLE) in black South Africans. METHODS: HLA-DRB1 genotype frequencies assigned by polymerase chain reaction (PCR) amplification and sequence specific oligonucleotide probes were compared between 49 black SLE patients from Baragwanath Hospital and 87 ethnically matched controls. HLA-DQA1 and -DQB1 genotypes were also assigned in 45 of the SLE patients and 74 controls by PCR using sequence specific primers. RESULTS: HLA-DRB1*02 was increased in the patients compared with controls (odds ratio = 3.67; 95% confidence interval = 1.49 to 9.02; p < 0.005). HLA-DQB1*0201 was not associated with development of the disease itself, but was associated with the presence of Ro antibodies (p = 0.01). HLA-DRB1*03 was less strongly linked to DQB1*02 in this population than in white populations and was not associated with SLE. CONCLUSIONS: In black South Africans there is evidence for a locus on DR2 haplotypes contributing to SLE. Another gene, possibly HLA-DQB1*02, not linked to DR2 is involved in the subset of patients exhibiting Ro antibodies.

Adolescent↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗