PubMed Health⌕ Search

Biomedical subjects

H Schotte

Publications and source records attributed to H Schotte.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and immunological characteristics of patients with Sjögren's syndrome in relation to alpha-fodrin antibodies.

OBJECTIVES: To analyse the prevalence of alpha-fodrin antibodies in patients with primary (pSS) and secondary Sjögren's syndrome (sSS) and the relation to clinical, serological and immunological features. METHODS: Serum IgA and IgG antibodies to the 120 kDa alpha-fodrin were determined by ELISA technique in 62 pSS patients and 28 sSS patients. Results were correlated with clinical symptoms and laboratory findings as well as with the HLA-DR genotype. Additionally, antibody concentrations were correlated with the numbers of peripheral blood mononuclear cells (PBMCs) secreting interleukin (IL)-6, IL-10, interferon-gamma (INF)-gamma, and tumour necrosis factor-alpha determined by ELISPOT analysis. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Healthy age- and sex-matched volunteers served as controls. RESULTS: The sensitivity of IgA and IgG alpha-fodrin antibodies was 35 and 31%, respectively, in pSS patients. In sSS patients, the sensitivity was 29 and 21%, respectively. In pSS patients with IgG antibodies, recurrent parotid swelling was significantly more prevalent. Also the number of INF-gamma secreting PBMCs and the percentage of CD4/CD71+ lymphocytes as well as CD14/HLA-DR+ monocytes were significantly increased in this group compared with alpha-fodrin-negative patients or with controls. Interestingly, these patients also had a shorter disease duration. No association of alpha-fodrin antibodies with the HLA-DR genotype was found. CONCLUSION: Due to the low prevalence, serum antibodies to alpha-fodrin turned out to be of limited diagnostic value in our study. However, our data suggest that IgG antibodies to alpha-fodrin are indicative of clinical and immunological activity in pSS especially in patients with shorter disease duration and may thus serve as a marker of disease activity.

Adult↗
PubMed2005

[Cardiovascular monitoring of patients with systemic lupus erythematosus].

Accelerated atherosclerotic cardiovascular disease is increasingly recognized as a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Cardiac manifestations of SLE are frequent and can involve almost all components of the heart. Pulmonary hypertension often develops during the course of SLE. The high incidence of cardiovascular complications may justify a screening of SLE patients in order to ensure early diagnosis and therapy. Results of diagnostic procedures that detect coronary insufficiency, surrogates of atherosclerotic burden and echocardiographic findings are often abnormal in SLE. However, evidence to support a routine screening for cardiovascular disease is currently not available. Therefore, based on the recommendations that have been proposed for other conditions associated with cardiovascular disease, we suggest assessment of risk factors and the performance of echocardiography at least annually in asymptomatic SLE patients. If two or more risk factors are present, an exercise ECG is recommended. The benefit, however, of screening SLE patients for cardiovascular disease has to be confirmed in prospective studies.

Cardiovascular Diseases↗
PubMed2005

[Four-year observation of etanercept therapy for rheumatoid arthritis in a single German center].

The tumor necrosis factor blocking agent etanercept is effective in the treatment of chronic inflammatory diseases. Previously published studies provided no evidence for an elevated frequency of severe adverse events under therapy. The present work documents efficacy and safety of long-term treatment with etanercept up to four years in 29 patients with rheumatoid arthritis in single German study center. Follow-up examinations were conducted at monthly intervals. The response was assessed in an intention-to-treat analysis (last observation carried forward) according to the ACR and EULAR criteria. The evaluation is based on 95 patient years, the median observation period was 50 (4-52) months. After four years, 21 patients were still in the study. Reasons for study dropouts were inefficacy (n=3), severe adverse events (n=1), long distance to study center (n=2), scheduled surgery (n=1), and desire for pregnancy (n=1). Morning stiffness, the number of painful and swollen joints, C-reactive protein, erythrocyte sedimentation rate, and DAS28 significantly decreased within 6 months. At their most recent visit, 26 patients (90%) had achieved the ACR20, 17 patients (59%) the ACR50, and 6 patients (21%) the ACR70 criteria. Subject to the EULAR criteria, 14 patients (48%) responded well and another 12 patients (41%) moderately well. Severe adverse events occurred in the form of a sigma perforation with subsequent sepsis (week 17), suture insufficiency (twice) following rupture of an Achilles tendon (weeks 3 and 9), pneumonia (week 121), and breast cancer (week 197). In our patients, long-term treatment with etanercept continued to be effective and safe up to four years. Severe adverse events were rare and not more frequent than expected. For the detection of uncommon or late occurring severe adverse events under the treatment with biologic agents, documentation in central registers should be encouraged.

Adult↗
PubMed2005

[Early diagnosis in patients with systemic lupus erythematosus (SLE)].

Early diagnosis in patients with systemic lupus erythematosus (SLE) remains a challenge even to experienced rheumatologists. This is due to the diversity of presentation with single or multiple manifestations and the variable course. In contrast to the considerable progress in treatment modalities no reliable diagnostic marker has been developed in the last years. So the diagnosis is made largely on clinical grounds with great awareness of anamnestic features, thoroughly performed physical examination supported by laboratory and organspecific tests. The 1997 revised ACR classification criteria are of great value, though they do not satisfy in every single case. With respect to the potentially life or organ threatening course of SLE a good interdisciplinary cooperation of general practitioners and specialists with rheumatologists is of special importance.

Diagnosis, Differential↗
PubMed2004

Interleukin 10 promoter microsatellite polymorphisms are associated with response to long term treatment with etanercept in patients with rheumatoid arthritis.

OBJECTIVES: To analyse the association of interleukin 10 (IL10) promoter polymorphisms, which have been shown to be related to IL10 secretion capacity, with the response to long term treatment with etanercept in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with active RA were treated for up to 4 years (median 39 months, range 3-52) with stable doses of etanercept as monotherapy. Treatment response was assessed as defined by the EULAR criteria in an intention to treat analysis, with the last observation carried forward. IL10 promoter microsatellite polymorphisms IL10.R and IL10.G were genotyped by fragment length analysis in patients and 189 healthy controls matched for ethnicity, age, and sex. Haplotypes were reconstructed using a method based on bayesian, coalescent theory with the PHASE software. RESULTS: IL10 microsatellite polymorphisms were not associated with susceptibility to RA. When patients with good treatment response (n = 25) were compared with patients with moderate (n = 17) or no response (n = 8), a significantly different distribution of the prevailing alleles R2, R3 and G9, G13, respectively, became evident. Good treatment response was associated with carriage of the R3 allele or R3-G9 haplotype, whereas the allele G13 and the haplotype R2-G13 predominated in patients with moderate or no response. CONCLUSION: Genotyping of the IL10 promoter microsatellites may be useful in predicting the clinical response to etanercept in patients with RA. The high prevalence of the presumptive IL10 low producer allele R3 in patients with a favourable response suggests that IL10 promotes disease activity in RA under the specific condition of tumour necrosis factor antagonism.

Adult↗
PubMed2004

Interleukin-10 promoter microsatellite polymorphisms in systemic lupus erythematosus: association with the anti-Sm immune response.

OBJECTIVES: Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). In vitro IL-10 secretion has previously been related to haplotypes of the IL-10 promoter microsatellite polymorphisms IL10.R and IL10.G. Published data concerning the association of IL10.G alleles with susceptibility to SLE are inconsistent in different ethnic populations. We analysed the association of IL-10 promoter microsatellite polymorphisms with disease susceptibility and manifestations in German Caucasian patients with SLE. METHODS: Two hundred and ten (210) SLE patients fulfilling the 1997 revised ACR criteria and 158 ethnically, age- and sex-matched healthy controls were genotyped for the IL-10 promoter microsatellite polymorphisms by fragment length analysis. Haplotypes were reconstructed using a Bayesian coalescent theory-based method with PHASE software. Allele and haplotype distributions were compared between patients and controls and between subgroups of patients with different clinical and immunopathological findings. RESULTS: In the study population no significant associations of individual IL10.R and G alleles or their haplotypes with susceptibility to SLE or major clinical manifestations were observed. By contrast, alleles G14 and G15 and haplotypes R2-G14 and R2-G15 were significantly over-represented in anti-Sm antibody-positive patients. CONCLUSIONS: The IL-10 promoter microsatellite polymorphisms and their haplotypes do not constitute a major risk factor for SLE in German Caucasians. However, the identification of genetic markers such as the IL-10 high-response haplotype R2-G14 predisposing for the production of anti-Sm antibodies may help to elucidate the conditions that lead to the development of SLE.

Adolescent↗
PubMed2004

Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis.

OBJECTIVES: To determine the influence of etanercept treatment on the number of peripheral blood mononuclear cells (PBMC) secreting immunoregulatory key cytokines and the correlation of these cell counts with treatment response in patients with rheumatoid arthritis (RA). METHODS: Nineteen patients with RA were treated with etanercept as monotherapy. Frequencies of PBMC secreting cytokines were determined by ELISPOT analysis before and after 9 months of therapy and compared with values for healthy controls (HC). The clinical outcome was assessed as defined by the ACR criteria. RESULTS: Fifteen patients fulfilled the ACR20, seven patients the ACR50 and two patients the ACR70 criteria. Initially elevated numbers of tumour necrosis factor-alpha- and interleukin (IL)-1beta-secreting PBMC were reduced to HC levels, and normal or low numbers of IL-6- and interferon-gamma (IFN-gamma)-secreting PBMC were reduced below HC levels. The number of IL-10-secreting PBMC did not differ from that in HC and did not change significantly over time. The pretreatment IFN-gamma:IL-10 ratio correlated to reduction in the tender and swollen joint counts. CONCLUSIONS: Long-term treatment with etanercept in patients with RA significantly reduces the numbers of proinflammatory cytokine-secreting PBMC, while the number of IL-10-secreting cells is unaffected. Although the changes described did not affect the safety or efficacy of etanercept therapy, these alterations may account for the long-term systemic effects. The pretreatment IFN-gamma:IL-10 ratio may be of prognostic value in predicting the improvement in joint symptoms.

Adult↗
PubMed2004

Increased frequency of GM-CSF secreting PBMC in patients with active systemic lupus erythematosus can be reduced by immunoadsorption.

An objective was to determine the frequency of GM-CSF secreting peripheral blood mononuclear cells (PBMC) in patients with active systemic lupus erythematosus (SLE) and their relation to other cytokine secreting PBMC, activation markers on lymphocytes/monocytes, clinical manifestations and anti-dsDNA antibodies. A second objective was to further investigate the influence of immunoadsorption (IA) therapy on these parameters. The number of GM-CSF, interleukin-1beta (IL-1beta), IL-6, interferon-gamma (INF-gamma) or tumour necrosis factor-alpha (TNF-alpha) secreting PBMC was assessed by ELISPOT assay in 10 patients with active SLE. Further, the expression of activation markers on lymphocytes and monocytes was determined by flow cytometry. Three courses of IA were performed in the patients. Seventeen healthy, age- and sex-matched volunteers served as controls. GM-CSF secreting PBMC were significantly increased whereas INF-gamma secreting cells were decreased in SLE patients. The expression of CD71 (transferrin receptor) on CD4+ T-cells and of the costimulatory molecule CD86 on B-lymphocytes was significantly increased in SLE patients. GM-CSF secreting PBMC and CD4+/CD71+ T-cells correlated with anti-dsDNA antibody titres and decreased towards levels of controls during IA. Disease activity and anti-dsDNA autoantibody titres were significantly reduced after the treatment. Our results demonstrate significant alterations of cellular and humoral immunity in SLE patients. The impaired immunity can be modulated by IA. Thus IA may prove an immunomodulatory therapeutic option in addition to the mere depletion of anti-dsDNA autoantibodies.

Adult↗
PubMed2003

Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjögren's syndrome.

OBJECTIVE: To study systemic alterations of cytokine secreting peripheral blood mononuclear cells (PBMC) in primary Sjögren's syndrome (pSS) and their relation to common clinical and immunological manifestations of this disease. METHODS: PBMC spontaneously secreting tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and interleukin 6 (IL6) were assessed by enzyme linked immunospot (ELISPOT) analysis in a cohort of 31 patients with pSS fulfilling the modified European classification criteria. Nineteen healthy volunteers served as controls. ELISPOT results were correlated with glandular and extraglandular manifestations and autoantibody titres-that is, rheumatoid factor (RF) isotypes, anti-Ro/SS-A, anti-La/SS-B as determined by an enzyme linked immunosorbent assay (ELISA) technique. RESULTS: The number of TNFalpha and IL1beta secreting cells was significantly higher in patients with pSS than in controls. No differences were detected in the number of IL6 secreting PBMC. Patients with recurrent parotid swelling (RPS) had a significantly increased number of IL1beta secreting PBMC. Moreover, the number of IL1beta secreting PBMC correlated with the disease duration (r(s)=0.479; p<0.01) and with the concentration of IgM RF (r(s)=0.63; p<0.01) and IgG RF (r(s)=0.42; p<0.05). Other autoantibodies did not correlate with cytokine secreting PBMC. CONCLUSION: The increased systemic secretion of IL1beta and TNFalpha in patients with pSS points to a pathogenic impact of these cytokines in this autoimmune disease. In particular the correlation of IL1beta secreting PBMC with RPS and RF production indicates that IL1beta is a crucial regulator in the development of local and systemic disease manifestations.

Adult↗
PubMed2003

The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus.

Lymphocyte production of transforming growth factor (TGF)-beta1 is decreased in systemic lupus erythematosus (SLE). The lack of this immunoregulatory cytokine may contribute to the characteristic T cell disregulation and aberrant B cell stimulation in SLE patients. The less common C allele of the TGFB1 polymorphism (G915C) is associated with a lower TGF-beta1 production capacity. We performed a population-based case-control study to analyse the impact of this polymorphism on disease susceptibility, on clinical SLE manifestations and autoantibody production. A total of 203 German Caucasian SLE patients (fulfilling the 1982 ACR disease duration 11.5 +/- 7.0 years) and 158 ethnically, age- and sex-matched healthy controls were genotyped with a mutagenically separated polymerase chain reaction. There were no significant differences in the genotype distribution and allele frequencies between patients (915 C = 0.08) and healthy controls (915 C = 0.10). Comparing subgroups of patients, we found no association of major disease manifestations or specific autoantibodies with TGFB1 genotypes or alleles. The TGFB1 polymorphism (G915C) neither significantly contributes to the disease susceptibility, nor predisposes to clinical and immunological manifestations typical of SLE. Further studies are needed to corroborate the pathogenic role of TGF-beta1 in SLE patients and to identify the precise genetic elements controlling its production.

Adult↗
PubMed2001

Interleukin-6 promoter polymorphism (--174 G/C) in Caucasian German patients with systemic lupus erythematosus.

BACKGROUND: A biallelic polymorphism (--174 G/C) within the interleukin-6 (IL-6) promoter reportedly has functional importance through the modulation of IL-6 expression in vitro and in vivo. METHODS: We performed a population-based case-control study to analyse the association of the --174 G/C polymorphism with disease susceptibility and clinical manifestations in 211 German patients with systemic lupus erythematosus (SLE). RESULTS: There were no significant differences in allelic and genotypic frequencies between patients and healthy controls. Comparing patients with various disease manifestations, we found an association of the --174 G allele with discoid skin lesions (Pc=0.034) and anti-histone antibodies (Pc=0.009). CONCLUSIONS: The IL-6 promoter polymorphism --174 G/C does not contribute significantly to disease susceptibility, but predisposes to distinct clinical and immunological features. A genetically determined high IL-6 response may have a pathogenic role under these conditions.

Adult↗
PubMed2001

Cat scratch disease (bartonellosis) mimicking an SLE flare.

Only recently Bartonella species have been recognized as important human pathogens. Cat scratch disease (CSD), caused by infection with Bartonella henselae, shows a steady increase in the number of cases throughout the world. We report a case of an 18-year-old woman with systemic lupus erythematosus (SLE) who presented with ongoing fever, arthralgias and loss of weight which did not respond to increasing doses of corticosteroids. After exclusion of common infections a photograph of her cat in combination with scratch marks on her arms finally led to the suspicion of CSD. This tentative diagnosis was confirmed serologically. Under clarithromycin treatment the patient rapidly responded and her temperature dropped within 2 days.

Adolescent↗
PubMed1999

Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial.

OBJECTIVE: To investigate the effectiveness and safety of mycophenolate mofetil in patients with systemic lupus erythematosus who were inadequately controlled with corticosteroids, antimalarials, and other immunosuppressive agents. METHODS: Ten patients with systemic lupus erythematosus (SLE) were treated with 1500-2000 mg mycophenolae mofetil (MMF) daily for a median observation time of 11. 2+/-2.4 (8-16) months in an open clinical trial. The effectiveness and safety of treatment were analyzed using an established disease activity score, clinical status, and laboratory parameters. RESULTS: All patients improved under treatment with no or only minor side effects. The disease activity score (SLAM) decreased statistically significantly from a median of 15.6+/-5.5 to 9.9+/-4.1 after three months (P<0.01) and to 8.0+/-3.3 after six months (P<0.01). Hematologic parameters did not change significantly whereas a reduction of inflammatory markers was observed. Four patients with SLE-nephritis already treated with cyclophosphamide pulse therapy continuously showed a slight improvement of renal function. Prednisolone dosages could be reduced significantly from a median level of 10.0+/-5.1 mg/d before treatment to 4.6+/-3.5 mg/d after six months (P<0.01). CONCLUSION: Mycophenolate mofetil is a promising option in immunosuppressive treatment of patients with moderate and severe systemic lupus erythematosus who did not show a satisfactory response to other immunosuppressives.

Adolescent↗
PubMed1998

Prospective randomized trial of two different immunoadsorbers in severe systemic lupus erythematosus.

Experiences with extracorporeal therapy in systemic lupus erythematosus have been published over the last 20 years and more. In addition to plasmapheresis, specific adsorption columns have been developed to deplete pathogenic antibodies and immune complexes in the plasma of patients with SLE. We conducted a prospective randomized trial to compare the efficacy of a disposable adsorption column, which contained a specific ligand, phenylalanine (IMPH-350|Pt, Diamed, Köln, Germany) with a regenerable Ig-adsorbing column containing sheep anti-human antibodies (Ig-Therasorb|Pt, Therasorb, München, Germany). Twenty SLE patients inadequately controlled with corticosteroids, anti-malarials, azathioprine or cyclosporine A, had strong evidence of disease in general, or an organ related SLAM score. They were randomized to receive either a perfusion of IMPH-350, or Ig-Therasorb, immunoadsorbed with 2.5 ml of plasma, three times each. The treatment regime was repeated after 4 weeks when the response was limited or non-existent. Response was defined as a reduction in the SLAM score of at least 30%. SLAM scores in the IMPH group decreased from 14.3+/-5.6 to 9.2+/-6.2 after 1 month and to 9.4+/-3.9 after 6 months; corresponding scores in the Ig-Therasorb group were 18.3+/-5. 5 to 11.2+/-7.6, decreasing to 9.2+/-2.9. After 1 month, 8/10 patients in both groups showed a response; after 6 months, 5/10 patients in the IMPH-350 group and 8/10 in the Ig-Therasorb group fulfilled the response criteria. Reduction of dsDNA antibodies directly after treatment was 50.8+/-6.6% in the IMPH-350 group and 61.0+/-8.0% in the IgTherasorb group. Results indicate that immunoadsorption is an additional option in the treatment of severe SLE. Choice of type of immunoadsorber and immunosuppressive treatment has to take into account the severity and chronicity of common disease activity and organ involvement, as well as economic aspects.

Adult↗
PubMedDate not supplied

Extended haplotype analysis reveals an association of TNF polymorphisms with susceptibility to systemic lupus erythematosus beyond HLA-DR3.

OBJECTIVE: To study the relative contribution of tumour necrosis factor (TNF) and HLA-DRB1 polymorphisms to the genetic susceptibility to systemic lupus erythematosus (SLE) via an extended haplotype analysis. METHODS: We performed an association study in 205 unrelated German Caucasian patients with SLE fulfilling the 1997 revised American College of Rheumatology (ACR) criteria. Healthy age-, ethnically- and sex-matched individuals (n = 157) served as controls. HLA-DRB1 typing was performed by a sequence-specific oligonucleotide hybridisation assay. Two TNF single nucleotide polymorphisms (SNPs) and two multiallelic microsatellites were analysed by mutagenically separated polymerase chain reaction (PCR) or fragment length analysis, respectively. Extended haplotypes were reconstructed with the PHASE software. RESULTS: Alleles for all polymorphic loci studied and the most frequent haplotypes showed a significantly different distribution between SLE patients and controls. The alleles HLA-DR2, DR3, TNFd1, TNF2, TNFB*1, and TNFa2, designated as risk alleles, and the extended haplotypes DR3-TNFd1-TNF2-TNFB*1-TNFa2 and DR2-TNFd3-TNF1-TNFB*2-TNFa11 prevailed in SLE patients. TNF risk alleles were strongly positively linked with HLA-DR3 and negatively linked with HLA-DR2. Thus, in HLA-DR3 haplotypes individual effects of TNF polymorphisms could not be resolved. By contrast, HLA-DR2 showed an association with SLE independently of TNF risk alleles, while the risk increased further when they were present. In haplotypes lacking HLA-DR2 and DR3, the alleles TNFdl and TNF2 contributed independently to SLE susceptibility. CONCLUSION: Extended haplotype analysis revealed HLA-DR3 independent associations of TNF polymorphisms with susceptibility to SLE. Haplotypes that have been shown to be associated with different TNF-alpha production capacity may prevail in different disease subgroups.

Adolescent↗
PubMedDate not supplied

Cogan's syndrome: organ-specific autoimmune disease or systemic vasculitis? A report of two cases and review of the literature.

Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory eye disease and vestibuloauditory symptoms. Typically, young adults suffer from interstitial keratitis and sudden onset of tinnitus and hearing loss. Few cases (around 150) have been published and thus it is difficult to determine the percentage of patients with underlying systemic disorders such as systemic vasculitis. The variety of systemic manifestations is large and includes fever, splenomegaly, lymphadenopath, and musculoskeletal complaints. Systemic vasculitis can be seen in around 10% of cases and may involve the large vessels, appearing as Takayasu-like vasculitis with affection of the aortic valve but also the coronary arteries and the small kidney vasculature. Evaluating the exact extension of the systemic features determines the choice of treatment. While corticosteroids have proved to be of short-term benefit, long-term treatment with immunosuppressive drugs is controversial. Auditory function in deaf patients has often been restored successfully with cochlear implants. To illustrate the nature of the syndrome, we present two patients with a wide clinical spectrum of symptoms from local disease restricted to the eyes and ears to a widespread vasculitis affecting arteries of the brain, kidney and the upper and lower extremities. We then review the typical aspects as well as the etiology of the disease.

Adolescent↗