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J Sieper

Publications and source records attributed to J Sieper.

At least 109 records · Page 6Linked to original sources
PubMed2001

Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism.

OBJECTIVE: To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS: Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNgamma, TNFalpha, IL4, and IL10, and analysed by flow cytometry. TNFalpha production was related to the genotype of the TNFalpha promoter at the -308 and -238 polymorphisms. RESULTS: In peripheral blood the percentage of TNFalpha+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFalpha+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNgamma+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFalpha+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%). CONCLUSIONS: The lower T cell production of TNFalpha and IFNgamma shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFalpha production and, therefore, might be a marker for a protective haplotype.

Adult↗
PubMed2001

Low incidence of reactive arthritis in children following a salmonella outbreak.

OBJECTIVES: To assess the incidence of reactive arthritis (ReA) in an outbreak of salmonella infection in a large cohort of children in Germany. METHODS: A few days after the salmonella outbreak all parents of affected children and all paediatricians and general practitioners in the region were provided with detailed information about the possibility of ReA. Six weeks after the outbreak a telephone call was made to all general practitioners and paediatricians to identify patients with ReA. Ten weeks after the outbreak a questionnaire assessing symptoms of ReA was mailed to all parents, and after a period of 4 months paediatricians and general practitioners were contacted again to search for additional unreported cases of ReA. RESULTS: Of the 286 children (age range 11 months to 9 years) with diarrhoea and stool cultures positive for Salmonella enteritidis lysotype 8/7, not a single case of arthritis was reported over the 4 month period. However, six children (2%) had arthralgia of various duration (1 day to 6 weeks) with a single recurrence in one child. The joint pattern was oligoarticular and lower limb joints (knee/ankle) were affected exclusively. CONCLUSION: The incidence of ReA after salmonella infection in children appears to be very low which may be related to differences in the immune response between children and adults.

Arthritis, Reactive↗
PubMed2001

Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis.

OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.

Adolescent↗
PubMed2001

New treatment options in ankylosing spondylitis: a role for anti-TNFalpha therapy.

Anti-TNFalpha treatment seems to be highly effective in AS. The results available indicate that this treatment is at least as effective as in RA. Furthermore, because no other treatments are available for AS--in contrast with RA or psoriatic arthritis--infliximab may even become a first line immunosuppressive treatment in patients with severe active AS. A dose of 5 mg/kg body weight seems to be required and intervals between 6 and 12 weeks seem to be necessary depending on the disease activity. It remains to be seen what the long term effects will be, whether the patients benefit from long term treatment, and whether radiological progression and ankylosis can be stopped. Allergy, lupus-like diseases, and tuberculosis are rare side effects which need to be considered. At first glance, the possible benefits of anti-TNFalpha treatment seem to outweigh these shortcomings, including the high cost.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles.

Yersinia heat-shock protein 60 (Ye-hsp60) has recently been found to be a dominant CD4 and CD8 T cell Ag in Yersinia-triggered reactive arthritis. The nature of this response with respect to the epitopes recognized and functional characteristics of the T cells is largely unknown. CD4+ T cell clones specific for Ye-hsp60 were raised from synovial fluid mononuclear cells from a patient with Yersinia-triggered reactive arthritis. and their specificity was determined using three recombinant Ye-hsp60 fragments, overlapping 18-mer synthetic peptides as well as truncated peptides. Functional characteristics were assessed by cytokine secretion analysis in culture supernatants after specific antigenic stimulation. Amino acid positions relevant for T cell activation were detected by single alanine substitutions within the epitopes. Fragment II comprising amino acid sequence 182-371 was recognized by the majority of clones. All these clones were specific for peptide 319-342. Th1 clones and IL-10-secreting clones occurred in parallel, sometimes with the same fine specificity. The 12-mer core epitope 322-333 is a degenerate MHC binder and is presented to some T cell clones in a "promiscuous" manner. This epitope is almost identical with a B27-restricted CTL epitope of Ye-hsp60. Cross-reactivity of Ye-hsp60-specific T cell clones with self-hsp60 was not observed. In conclusion, an interesting Ye-hsp60 T cell epitope has been identified and characterized. It remains to be determined whether this epitope is also relevant in other reactive arthritis patients.

Adolescent↗
PubMed2000

Report on the Fourth International Workshop on Reactive Arthritis.

There are large differences in the antigenicity and biology of the ReA-associated bacteria. For induction of arthritis, the relevance seems to be only that antigenic material reaches the joint, alive or dead. If there is a common antigen, it has to be a highly conserved one. Bacterial hsp60 seems to be an immunodominant T cell antigen in ReA, but there must be other relevant antigens shared by these different bacteria. An ineffective immune response (for example, low production of TNFalpha) seems to contribute to the manifestations and course of ReA. Although arthritis can also occur in its absence, HLA-B27 plays an important role in the pathogenesis of ReA and the other SpA. Current data suggest that B27 probably acts as an antigen-presenting molecule for a still-unknown arthritogenic molecule. Comparison of ReA with IBD-associated arthritis suggests that there might indeed be a common antigen shared by ReA-associated bacteria and bacteria of the gut flora. CD8+ T cells seem to be important in ReA and other SpA. In some parts of the world, such as in Mexico, ReA could be a major predisposing cause of the development of AS. Antibiotic treatment is not effective, probably because the triggering bacteria are already dead or in a partly latent state at the time arthritis occurs. Based on this knowledge and on new technologies, it should be possible in future years to derive answers to the questions about ReA and the other SpA and, as a consequence, to find a cure.

Arthritis↗
PubMed2000

Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been detected in sacroiliac joint biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFalpha monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). METHODS: Eleven patients with AS of short duration (median 5 years, range 0.5-13 years) that had been active for at least 3 months (range 3-72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted > 1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. RESULTS: One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2-6 weeks after the third infusion revealed improvement in 2. Improvement of > or = 50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41-94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6-90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0-28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. CONCLUSION: These data suggest that anti-TNFalpha therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflammatory effect, prevents ankylosis remains to be determined.

Adult↗
PubMed2000

Association of genotypes affecting the expression of interleukin-1beta or interleukin-1 receptor antagonist with osteoarthritis.

OBJECTIVE: The majority of cytokines and growth factors known to be involved in cartilage metabolism are synthesized by the chondrocytes themselves. They are up-regulated in osteoarthritic (OA) cartilage, resulting in 2 opposite phenotypes, TNFalpha(high) and TNFalpha(low), that are characterized by an elevated number of tumor necrosis factor alpha (TNFalpha)-positive and interleukin-1beta (IL-1beta)-positive chondrocytes, respectively. To establish a hierarchy among the cytokines and growth factors expressed in articular chondrocytes, this study investigated cytokine genes for known polymorphisms that may contribute to the deregulated expression in OA cartilage. METHODS: Polymerase chain reaction techniques were performed either in a thermal cycler using standard methods or in a light cycler to analyze the frequencies of the TNFalpha (-308), IL-1 receptor antagonist (IL-1Ra) (intron 2), IL-1beta (exon 5), and IL-6 (-174) polymorphisms in 61 OA patients and 254 randomly chosen controls. RESULTS: For the TNFalpha(low) phenotype, a statistically significant association was found with the less frequent allele of IL-1beta, which carries a single-basepair substitution in exon 5 and may contribute to the characteristic increase in IL-beta-positive chondrocytes. In contrast, the TNFalpha(high) phenotype was significantly associated with the less frequent allele of IL-1Ra, which carries two 86-bp repeats in the second intron and is assumed to lead to an elevated expression of the antagonist. CONCLUSION: These results point to an association between the IL-1beta polymorphism and the TNFalpha(high) phenotype and between the IL-1Ra polymorphism and the TNFalpha(low) phenotype found in OA. Both associations suggest that IL-1beta may be more important than TNFalpha for the regulation of cytokine and growth factor expression in articular chondrocytes.

Alleles↗
PubMed2000

Analysis of the antigen-specific T cell response in reactive arthritis by flow cytometry.

OBJECTIVE: In reactive arthritis (ReA) a bacteria-specific T cell response to the triggering microbe is detected in synovial fluid (SF), and an impaired Th1 cytokine response has been described. The recent identification of immunodominant bacterial proteins/peptides and new technologies make a more detailed analysis of the immune response possible. The aim of the present study was to use these new techniques to determine the antigen-specific T cell frequency and the cytokine secretion pattern on stimulation with bacteria-derived recombinant proteins in the peripheral blood (PB) and SF from patients with ReA. METHODS: In 3 patients with Chlamydia-induced ReA and 2 patients with Yersinia-induced ReA, the SF T cell response was investigated after stimulation with the Chlamydia-derived proteins major outer membrane protein (MOMP) and heat-shock protein 60 (Hsp60) and the Yersinia-derived proteins 19-kd protein and Hsp60. In 3 of these patients, the PB T cell response was investigated in parallel. T cells were stimulated in whole blood or whole SF with antigen plus anti-CD28 for 6 hours, brefeldin A was added after 2 hours, and cells were fixed and stained with antibodies against the surface markers CD4 and CD69 and against the cytokines interferon-gamma (IFNgamma), tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-4. Positive cells were quantified by flow cytometry. RESULTS: In the 3 patients with Chlamydia-induced ReA, the antigen-specific T cell frequency (percentage of IFNgamma CD69 double-positive CD4+ T cells) in response to MOMP (mean +/- SD 1.2 +/- 1.38%) and to Hsp60 (1.21 +/- 1.45%) in SF was about the same. In the 2 patients with Yersinia-induced ReA, the mean +/- SD frequency was 0.66 +/- 0.36% in response to the Hsp60 and 03% +/- 0.22 in response to the 19-kd protein. In the 3 patients whose PB was evaluated, the corresponding T cell response was > or =10 times lower. In 2 patients with Chlamydia-induced ReA, antigen-specific IL-10-positive CD4+ T cells were detected in 0.10-0.23% of the CD4+ T cell subpopulation. CONCLUSION: The frequency of antigen-specific T cells to Chlamydia- and Yersinia-derived antigens in the SF of ReA patients is between 1:200 and 1:50. Both the chlamydial Hsp60 and MOMP are dominant T cell antigens in Chlamydia-induced ReA. In patients with Chlamydia-induced ReA, we detected antigen-specific IL-10 secretion, which might mediate an inhibition of effective bacterial clearance.

Adult↗
PubMed2000

Detailed analyses of periarticular osteoporosis in rheumatoid arthritis.

Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a cross-sectional study 23 women aged 30-76 years with early RA, mean disease duration 26 +/- 19 months, and 18 men aged 42-69 years, mean disease duration 24 +/- 25 months, were examined. All patients received antirheumatic therapy. The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest (MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II-V were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand BMD measurements, bone loss was pronounced in patients with a disease duration of 18-72 months at the subchondral regions of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. -23%, p<0.001, whole-hand -16%, p<0.001; men: mean BMD loss S.CH. -19%, p < 0.05, whole-hand -12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 +/- 90 m/s in RA vs 2137 +/- 35 m/s in young healthy controls (p <0.005); men AD-SOS 1956 +/- 87 m/s in RA vs 2146 +/- 41 m/s in young healthy controls (p <0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses.

Absorptiometry, Photon↗
PubMed2000

[Inception cohorts for spondyloarthropathies].

The spondyloarthropathies (SpA) are important inflammatory rheumatic diseases--not only because patients of young age are frequently involved. Ankylosing spondylitis, reactive arthritis, and undifferentiated spondyloarthropathy are prototypes of SpA which share several clinical features and the strong association with HLA B27. Despite its high prevalence there are many shortcomings in early diagnosis and therapy of SpA. The same is true for the knowledge on course, prognostic factors, and the socioeconomic consequences of these diseases. Furthermore, our knowledge about pathogenesis and therapy is still limited. Due to the known deficiencies in rheumatologic education, there are clear-cut deficiencies in the health care provided by general practitioners. The aim of the project presented here is to built up a cohort of early SpA patients to learn about course and outcome of SpA. In this regard, special attention is paid to the inclusion of patients with juvenile SpA since AS starts frequently in the 2nd decade of life and because the clinical picture with more frequent peripheral joint involvement differs from AS of adult onset. Moreover, these cohorts play an essential role for other projects of the MedNet subdivision of infect-associated arthritides/spondyloarthropathies in which studies on diagnosis, therapy, immunology, and genetics of the SpA performed.

Adult↗
PubMed2000

Imaging of sacroiliitis.

Inflammation of one or both sacroiliac joints is a characteristic feature of patients with spondyloarthropathies (SpA). Sacroiliitis often leads to inflammatory back pain (IBP). IBP and asymmetric peripheral arthritis of the lower limbs are the main clinical symptoms and criteria for classification and diagnosis of SpA in which sacroiliac joints are uni- or bilaterally affected with an intensity ranging from mild to very severe inflammation resulting in partial or complete ankylosis Sacroiliitis is a very frequent feature of undifferntiated SpA. In ankylosing spondylitis (AS) inflammation in the axial skeleton occurs rarely in the absence of sacroiliitis. Objective evidence of sacroiliitis obtained by imaging procedures, especially x-rays, has always been part of diagnostic and classification criteria for AS. This is in contrast to spinal radiography which, however, has been recently included in a core set of outcome items to be assessed in clinical studies. In early and acute stages of sacroiliitis the diagnosis can be difficult because conventional radiographs -- which are known to have considerable intra- and interobserver variability -- may be normal. Since IBP is not a specific indicator of sacroiliitis there is need for valuable imaging techniques. Scintigraphy lacks specificity. Computed tomography (CT) is a very good method to demonstrate already established bony changes and magnetic resonance imaging (MRI) has the advantage of combining a good visualisation of the complicated anatomy of the sacroiliac joint with the ability to localise different degrees of inflammation and oedema and prove a possible spread to muscles as it occurs in septic sacroiliitis, an important differential diagnosis.

Diagnosis, Differential↗
PubMed2000

The possible role of myocardial biopsy in systemic sclerosis.

The histopathological features of heart involvement in systemic sclerosis (SSc) are not widely known. In internal and transplantation medicine, myocardial biopsies are increasingly used to diagnose cardiomyopathies including myocarditis. In two SSc patients presenting with dyspnoea with no evidence of pulmonary involvement, the cause of the compromised heart function was sought by myocardial biopsy. Immunohistological analysis revealed an increased number of CD3+ + T cells indicating myocarditis in one, and increased amounts of fibroblasts in both SSc patients. The authors think that myocardial involvement in SSc should be differentially evaluated and they propose the use of myocardial biopsies as a tool to distinguish between inflammatory and fibrotic forms of heart involvement in SSc patients.

Biopsy↗
PubMed2000

Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis- cellularity correlates with the degree of enhancement detected by magnetic resonance imaging.

OBJECTIVE: Sacroiliitis is a hallmark of the spondyloarthropathies (SpA). The degree of inflammation can be quantified by magnetic resonance imaging (MRI). The aim of this study was to further elucidate the pathogenesis of SpA by quantitative cellular analysis of immunostained sacroiliac biopsy specimens and to compare these findings with the degree of enhancement in the sacroiliac joints (SJ) as detected by dynamic MRI. METHODS: The degree of acute sacroiliitis detected by MRI after intravenous administration of gadolinium-DTPA was quantitatively assessed by calculating the enhancement observed in the SJ and chronic changes were graded as described in 32 patients with ankylosing spondylitis (n=18), undifferentiated SpA (n=12) and psoriatic arthritis (n=2). Back pain was graded on a visual analogue scale (VAS, 0-10) and disease duration (DD) was assessed. Shortly after MRI, SJ of patients with VAS > 5 were biopsied guided by computed tomography. Immunohistological examination was performed using the APAAP technique; only whole sections > 3 mm were counted. RESULTS: By MRI, chronic changes </= grade II were detected in nine patients (group I, DD 2.5 (SD 2.9) years) and > II in 13 patients (group II, DD 7.3 (SD 4.8) years), while enhancement < 70% was found in eight (group A, DD 5.6 (SD 3.3) years) and > 70% in 12 patients (group B, DD 4.7 (SD 5.8) years). The relative percentage of cartilage (78-93%), bone (7-18%) and proliferating connective tissue (1-4%) was comparable between the groups (range). There were more inflammatory cells in group I compared with group II (mean (SD) 26.7(20.1) versus 5.3 (5. 2), p=0.04) and group A compared with B (21.8 (17.3) versus 6.0 (5. 6), p=0.05) cells/10 mm(2)), T cells (10.9 (8.5)) being slightly more frequent than macrophages (9.6 (16.8/10 mm(2))). Clusters of proliferating fibroblasts were seen in three and new vessel formation in seven cases. CONCLUSION: This study shows that T cells and macrophages are the most frequent cells in early and active sacroiliitis in SpA. The correlation of cellularity and MRI enhancement provides further evidence for the role of dynamic MRI to detect early sacroiliitis.

Acute Disease↗
PubMed2000

Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4.

OBJECTIVE: This study was performed to assess whether there is any change in the T cell cytokine pattern in early rheumatoid arthritis (RA) patients treated with methotrexate (MTX) and whether the lymphocytic cytokine pattern correlates with disease activity. METHODS: Eight patients with RA (disease duration < six months) were studied serially before, after three, and after six to nine months of treatment with MTX for the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 4 (IL4) and interleukin 10 (IL10) by intracellular staining of T cells derived from peripheral blood. Response to treatment was assessed by the modified disease activitiy score. RESULTS: The clincial response was accompanied by a significant decrease of TNFalpha positive CD4(+) T cells from a median of 8.53% (interquartile range 5.83-10.91%) before treatment to 6.17% (2.15-6.81%) after six to nine months of treatment (p=0.021). Inversely, IL10 positive T cells increased from a median of 0.65% (interquartile range 0.6-0.93%) to a median of 1. 3% (1.22%-1.58%) after six to nine months of treatment (p=0.009). No significant change in the percentage of INFgamma positive T cells and a small decrease of IL4 positive T cells during treatment were observed. The percentage of IL4 positive CD4(+) T cells before treatment correlated with disease activity after six to nine months (r= -0.7066; p=0.05). CONCLUSIONS: During treatment of RA with MTX the percentage of TNFalpha producing T cells decreases whereas that of IL10 producing T cells increases. This may affect macrophage activation and, therefore, may represent a regulatory mechanism relevant to disease remission. Furthermore, the percentage of IL4 positive CD4(+) T cells at disease onset may be a useful prognostic marker.

Antirheumatic Agents↗