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- Brisslert, Mikael, 1974, et al.
(författare)
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Intra-peritoneal sRAGE treatment induces alterations in cellular distribution of CD19(+), CD3 (+) and Mac-1 (+) cells in lymphoid organs and peritoneal cavity.
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 351:1, s. 139-48
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Tidskriftsartikel (refereegranskat)abstract
- Receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds a variety of pro-inflammatory ligands. Its soluble form, sRAGE, can compete for ligand binding and thereby have an anti-inflammatory effect. We have recently reported that sRAGE also exerts pro-inflammatory and chemotactic properties suggesting a dual role for sRAGE in immune modulation. Our present aim was to analyse the immunomodulatory properties of sRAGE in vivo with respect to acquired immunity. Naive mice were treated intra-peritoneally with sRAGE and cells from peritoneal lavage, spleens and bone marrow were examined. Mice treated with sRAGE displayed an increased leucocyte count in the peritoneal cavity, enlarged spleens and increased cellularity compared with vehicle-treated animals. Furthermore, sRAGE-treated mice had a significantly increased frequency and number of CD19(+) B cells in spleen and a reduced frequency of CD19(+) B cells in bone marrow compared with controls. Functionally, splenocytes from sRAGE-treated mice showed elevated IgG production and up to a four-fold increased IgM secretion compared with control animals and produced significantly higher levels of interleukin-10, interferon-γ and interleukin-6 in response to lipopolysaccharide stimulation. Our results suggest that sRAGE has immunomodulatory properties, since intra-peritoneal administration of sRAGE into healthy mice leads to rearrangements in cellular composition in the bone marrow and spleen. Moreover, the administration of sRAGE directs B cells into the spleen and towards differentiation. Our novel findings indicate that sRAGE exerts an effect on the cells of adaptive immunity.
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| 2. |
- Fei, Ying, et al.
(författare)
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The combination of a tumor necrosis factor inhibitor and antibiotic alleviates staphylococcal arthritis and sepsis in mice.
- 2011
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:3, s. 348-57
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Tidskriftsartikel (refereegranskat)abstract
- (See the editorial commentary by Chow, on pages 332-4) Background.Despite advances in medical practices, in recent decades permanent reductions in joint function have not been achieved, and the high mortality rate of patients with staphylococcal septic arthritis has not substantially improved. Methods.We evaluated the effects of a combined tumor necrosis factor (TNF) inhibitor and antibiotic therapy on the course of Staphylococcus aureus arthritis and sepsis in mice. Results.Treatment with the combination of a TNF inhibitor and an antibiotic resulted in a quicker relief of clinical arthritis in mice with septic arthritis, compared with an antibiotic monotherapy. Both histopathologically verified synovitis and the extent of joint destruction were reduced by this combined treatment. Importantly, anti-TNF treatment significantly improved the survival rate of mice with S. aureus sepsis and staphylococcal enterotoxin shock syndrome; this effect might be the result of a partial restoration of the hemostatic balance between coagulation and fibrinolysis. Finally, we demonstrated that anti-TNF treatment downregulates high-mobility group protein B1 in staphylococcal enterotoxin shock syndrome. Conclusions.Thus, simultaneous systemic TNF inhibition and antibiotic therapy has beneficial effects on the outcome of S. aureus arthritis and sepsis in a mouse model, suggesting that the combination of a TNF inhibitor and antibiotics represents a novel therapeutic strategy for the treatment of staphylococcal infections.
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| 3. |
- Jovancevic, Boja, 1970, et al.
(författare)
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Anti B-cell therapy against refractory thrombocytopenia in SLE and MCTD patients: long-term follow-up and review of the literature.
- 2013
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 22:7, s. 664-74
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Tidskriftsartikel (refereegranskat)abstract
- Objective The objective of this study was to retrospectively evaluate the clinical and immunological effects of anti-B cell treatment in patients with systemic lupus erythematosus (SLE) and mixed connective-tissue disease (MCTD) with autoimmune thrombocytopenia (AITP) refractory to conventional immunosuppressive treatment. Methods Rituximab (RTX) was added to the ongoing treatment of 16 patients (median age 36 years, range 17-84, all female) with treatment-resistant AITP. Thirteen patients had SLE and three had MCTD. RTX was given intravenously on four occasions during four consecutive weeks at a dose of 375mg/m(2). Clinical and laboratory disease activity variables recorded at every follow-up visit were analyzed. Results The median disease duration before RTX treatment was nine years (range 0.2-27) and the median post-treatment follow-up time was 28 months (range 3 to 92). Ten patients (63%) were treated repeatedly with RTX during the follow-up period. Complete depletion of B cells was achieved in 94% of cases one month after RTX treatment. A significant increase (p=0.0001) of platelet counts was seen already after one month (median 58×10(9)/ml vs 110×10(9)/ml) whereas within three months platelet counts normalized in 10 patients (median 223×10(9)/ml). Three patients did not respond to RTX treatment (median platelet count 69×10(9)/ml). High titers of anti-platelet antibodies were detected in seven patients before RTX treatment, and the autoantibody titers decreased significantly (p<0.03) after RTX treatment in six of these patients who also achieved complete remission. A review of the literature revealed 24 articles including 18 case reports, one retrospective cohort study and five prospective studies documenting the outcomes of 65 RTX-treated patients with SLE- or MCTD-related thrombocytopenia with an overall treatment response rate of 80%. In conclusion, these findings indicate that RTX is an additional potent therapeutic treatment option for SLE patients with AITP refractory to conventional immunosuppressive treatment whereas best response may be expected in patients with high titers of anti-platelet antibodies at baseline.
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| 4. |
- Mörck, Boel, et al.
(författare)
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Infliximab Dose Reduction Sustains the Clinical Treatment Effect in Active HLAB27 Positive Ankylosing Spondylitis: A Two-Year Pilot Study
- 2013
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861.
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Tidskriftsartikel (refereegranskat)abstract
- The rationale of the study was to evaluate the efficacy of infliximab (IFX) treatment in patients with ankylosing spondylitis (AS) and to determine whether IFX dose reduction and interval extension sustains the treatment effect. Nineteen patients were included and treated with IFX 5mg/kg every 6 weeks for 56 weeks. All patients concomitantly received MTX with median dose 7.5mg/weekly. During the second year, the IFX dose was reduced to 3mg/kg every 8 weeks. Eighteen patients completed the 1-year and 15 patients the 2-year trial. The >= 50% improvement at week 16 from baseline of BASDAI was achieved in 16/19 (84%) patients. Significant reductions in BASDAI, BASFI, and BASMI scores, decrease in ESR and CRP, and improvement in SF-36 were observed at weeks 16 and 56. The MRI-defined inflammatory changes in the sacroiliac joints disappeared in 10/15 patients (67%) already at 16 weeks. IFX treatment effect was sustained throughout the second year after IFX dose reduction and interval extension. We conclude that IFX treatment is effective in well-established active AS and a dose reduction sustains the treatment effect. These observations are of clinical importance and open the opportunity to reduce the drug costs. This trial is registered with ClinicalTrials.gov NCT01850121.
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| 8. |
- Pullerits, Rille, 1969, et al.
(författare)
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HMGB1: a possible prognostic marker for long-term outcome in children in juvenile idiopathic arthritis
- 2012
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Ingår i: Scandinavian Journal of Rheumatology. ; 41:S126, s. 25-26
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Konferensbidrag (refereegranskat)abstract
- Background: High-mobility group protein B1 (HMGB1), a nuclear protein and endogenous danger signal, has recently been implicated as an important pro-inflammatory mediator in adult rheumatoid arthritis (RA). Serum and synovial fluid HMGB1 levels are increased in patients with RA, HMGB1 is aberrantly expressed in inflamed synovial tissues, and treatment modalities blocking or down-regulating HMGB1 expression ameliorate joint inflammation in humans and mice. The role of HMGB1 in juvenile idiopathic arthritis (JIA) has not yet been not studied. To date, it is not known whether HMGB1 could have a predictive prognostic value in children with JIA. Objectives: Our aim was to analyse HMGB1 in patients with JIA and to determine its association with disease activity and long-term prognosis. Methods: Blood samples of 131 Estonian children with JIA (74 girls/56 boys, mean age 9.4±0.4 years, mean disease duration 9.1± 1.7 months) diagnosed according to International League of Associations for Rheumatology (ILAR) criteria were included in population-based incidence/prevalence study. From this study population, 38 patients (22 females/16 males) were recruited to a follow-up visit 10 years later. Clinical disease characteristics, inflammatory and immunological parameters at study start and at 10 years, as well as radiological disease progress at the 10-year follow-up, were recorded. HMGB1 levels at both time points were analysed using ELISA. Results: HMGB1 levels in serum (n = 131) at study start correlated with C-reactive protein (CRP). No association was found between HMGB1 levels and children’s age or disease duration. There were no significant differences in HMGB1 levels between groups regarding gender, antinuclear antibodies (ANA) and rheumatoid factor (RF) positivity, human leucocyte antigen (HLA) phenotype or JIA subtype. Patients (n = 38) recruited to the follow-up visit at 10 years were representative of the initial study population regarding sex and immunological and inflammatory parameters but had shorter disease duration at study start. HMGB1 levels in these patients correlated significantly with inflammatory markers: with CRP at study start and with neutrophil count at the 10-year follow-up. A strong positive correlation was found between HMGB1 levels at start and at 10 years in patients who had detectable skeletal ultrasound and/or X-ray changes. Patients with X-ray-verified changes displayed a fourfold higher median HMGB1 level at 10 years compared to patients without radiological changes. Conclusions: Our results suggest that HMGB1 is a marker of inflammatory activity in children with JIA. Higher serum levels of HMGB1 are related to destructive JIA and could be used as a negative prognostic marker at disease start.
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| 9. |
- Pullerits, Rille, 1969, et al.
(författare)
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Off-Trial Evaluation of the B cell-Targeting Treatment in the Refractory Cases of Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis: Long-Term Follow-Up from a Single Centre.
- 2012
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 76:4, s. 411-20
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate long-term clinical and immunological effects of anti-B cell treatment in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis refractory to conventional immunosuppressive treatment. Rituximab (RTX) was added to the ongoing immunosuppressive treatment in 29 patients with refractory ANCA-associated vasculitis. The disease activity was measured using Birmingham Vasculitis Activity Score/Wegener's granulomatosis (BVAS/WG score), and clinical laboratory variables were recorded. The median BVAS/WG score before treatment was 6 (IQR 3-8), and 28 patients (97%) had disease flare classified either severe (62%) or limited (34%). Six of 29 patients (21%) achieved a complete remission, and 12 (41%) had a treatment response with ≥50% decrease in BVAS/WG score at 6months. Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow-up period. Three patients had renal flare and were successfully re-treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea-subglottic granulomatous disease. RTX is a potent therapeutic option for ANCA-associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations.
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