| 1. |
- Adlesic, M., et al.
(author)
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Histamine in rheumatoid arthritis
- 2007
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In: Scand J Immunol. - : Wiley. - 0300-9475 .- 1365-3083. ; 65:6, s. 530-7
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by a persistent inflammation of the synovium, leading to the erosion of articular cartilage and bone. Synovial mast cells and their effector molecule, histamine, receive increased attention as mediators of joint inflammation. The aim of our study was to analyse levels of free histamine in serum and joint fluid of RA patients and to evaluate the potential inflammatogenic properties of histamine in vivo and in vitro. Histamine levels were measured by an ELISA in synovial fluid and sera of RA patients and of healthy controls. Histamine levels were also assessed in plasma of RA patients undergoing anti-TNF-alpha treatment. In the murine part of the study, histamine was injected intra-articularly in the knee joint of mice and the joints were subsequently analysed with respect to induction of inflammation. RA patients displayed significantly lower levels of histamine in circulation (0.93 +/- 0.16 ng/ml) compared with the healthy controls (1.89 +/- 0.45 ng/ml, P < 0.001). Locally, in synovial fluid the levels of histamine were even lower (0.37 +/- 0.16 ng/ml, P < 0.0006). Long-term anti-TNF-alpha treatment significantly increased circulating levels of histamine in RA patients. Our experiments on animals show that histamine on its own neither induces inflammation in the joint cavity nor influences the course of HMGB1 and peptidoglycan-induced joint inflammation. Based on our experimental and clinical studies we suggest that histamine lacks harmful properties in RA.
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| 2. |
- Lagerquist, Marie, et al.
(author)
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17Beta-estradiol expands IgA-producing B cells in mice deficient for the mu chain.
- 2008
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In: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:1, s. 12-7
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Journal article (peer-reviewed)abstract
- Oestrogen is not only a sex hormone but also an important regulator of the immune system. Expression of the heavy chain of IgM (mu) is essential for B-cell differentiation. However, a small number of IgA-positive B cells can be found in mice lacking the mu chain (muMT-/-). The aim of this study was to investigate the effects of oestrogen on this alternative B-cell pathway in muMT-/- mice. Our results clearly demonstrate that oestrogen increases the frequency of IgA-producing B cells in muMT-/- mice in both bone marrow and spleen cells. We also show that mature IgM-producing B cells are not required for oestrogen-mediated suppression of granulocyte-mediated inflammation or thymic involution. In conclusion, we demonstrate that 17beta-estradiol benzoate increases the frequency of IgA-producing B cells in muMT-/- mice, suggesting that oestrogen can influence the alternative B-cell pathway found in muMT-/- mice.
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| 3. |
- Akhiani, Aliasghar, 1957, et al.
(author)
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The nontoxic CTA1-DD adjuvant enhances protective immunity against Helicobacter pylori infection following mucosal immunization.
- 2006
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In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 63:2, s. 97-105
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Journal article (peer-reviewed)abstract
- Safe and efficacious adjuvants are much needed to facilitate the development of mucosal vaccines. Here, we have asked whether our nontoxic vaccine adjuvant, CTA1-DD, can enhance protective immunity against Helicobacter pylori infection. Intranasal immunizations with H. pylori lysate together with CTA1-DD-adjuvant induced significant protection in C57Bl/6 mice, almost as strong as similar immunizations using cholera toxin (CT)-adjuvant. Protection remained strong even at 8 weeks postchallenge and the bacterial colonization was reduced by 20-fold compared to lysate-immunized controls. Although CTA1-DD was designed to bind to B cells, microMT mice developed significant, but lower, level of protection following immunization. Intranasal immunizations with CT adjuvant in C57Bl/6 mice resulted in the development of severe postimmunization gastritis at 2 and 8 weeks postchallenge, whereas the degree of gastritis was substantially lower in the CTA1-DD-immunized mice. Protection induced by both CTA1-DD- and CT adjuvant was associated with a strong local infiltration of CD4(+) T cells in the gastric mucosa, and recall responses to specific Ag elicited substantial IFN-gamma production, indicating Th1-dominance. These findings clearly demonstrate that CTA1-DD adjuvant is a promising candidate to be further exploited in the development of a mucosal vaccine against H. pylori infection.
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| 4. |
- Albertsson, Per, 1964, et al.
(author)
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Differential locomotion of long- and short-term IL-2-activated murine natural killer cells in a model matrix environment.
- 2007
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In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:4, s. 402-9
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Journal article (peer-reviewed)abstract
- Tumour infiltration by activated natural killer (A-NK) cells is a pre-requisite for tumour eradication by adoptive NK cell transfer. Extravasated A-NK cells do not always succeed in reaching the crucial target cell conjugation. Therefore, we wished to study A-NK cell locomotion and interactions with melanoma cells in a matrix environment (Matrigel) by electron, confocal and fluorescence microscopy. Two distinct patterns of A-NK cell-mediated matrix disintegration were revealed during incubation of tumour cells and A-NK cells in Matrigel: (1) A-NK cells pre-cultured for 5 days altered the homogeneous texture of the Matrigel, an initial microporous appearance became a loose filamentous meshwork by 24 h. Matrix degrading protease inhibitors could not fully prevent this, but could delay the process; and (2) A-NK cells pre-cultured for 6 days or more, instead formed large excavations in the Matrigel leaving the remaining matrix less affected compared to the effects by the younger A-NK cells. By histochemical staining with Cupromeronic Blue, the excavations were shown to contain proteoglycan material. Protease inhibitors had no discernable effect on the development of the excavations. The conspicuous capacity of A-NK cells to disintegrate extracellular matrix and the formation of large excavations seems only partially to depend on matrix-degrading proteases. Formation of extracellular proteoglycan material is suggested to facilitate A-NK cell locomotion within a matrix environment.
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| 5. |
- Amu, Sylvie, 1978, et al.
(author)
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CD25-expressing B-lymphocytes in rheumatic diseases
- 2007
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In: Scand J Immunol. - : Wiley. - 0300-9475. ; 65:2, s. 182-91
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Journal article (peer-reviewed)abstract
- B cells play an important role in the development of autoimmune diseases due to their production of autoantibodies, antigen-presenting capacity and production of pro-inflammatory cytokines. The purpose of the present study was to analyse B cells from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, with respect to their expression of the IL-2 receptor (IL-2R) subunit CD25. Using flow cytometry, we found that CD25(+) B cells from RA patients expressed significantly higher frequencies of CD122 and CD132 than CD25(+) B cells from control subjects, indicating a fully functional IL-2R. These CD25(+) B cells also expressed higher frequencies of the co-stimulatory molecule CD80, whereas IgM and IgA expression was decreased compared with CD25(+) B cells from healthy controls. In addition B cells from SLE patients co-expressed CD25 together with CD80, CD122, and CD132, but to a lower degree IgD and IgM, when compared with healthy controls. Taken together, our results indicate that CD25(+) B cells from RA and SLE patients are in a highly activated state, display a more mature phenotype and suggest that this B cell subset may be involved in the pathogenesis of RA and SLE.
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| 6. |
- Bengtson, Per, 1971-, et al.
(author)
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Characterization of EBV-transformed B-cells established from an individual homozygously mutated (G329A) in the FUT7 alpha1,3-fucosyltransferase gene
- 2005
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In: Scand J Immunol. - : Wiley. ; 62:3, s. 251-8
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Journal article (peer-reviewed)abstract
- The alpha1,3-fucosyltransferase VII (Fuc-TVII) is involved in the biosynthesis of E- and P-selectin ligands such as sialyl Lewis x (SLe(x)) on human leukocytes. Recently, individuals were characterized carrying a missense mutation (G329A; Arg110-Gln) in the FUT7 gene encoding this enzyme. The mutated FUT7 construct produced a Fuc-TVII enzyme with impaired activity compared with the wildtype enzyme. Polymorphonuclear granulocytes from an individual carrying this mutation homozygously also showed a reduced expression of SLe(x). In the present study, we have established Epstein-Barr virus-transformed B-cell lines from this individual (SIGN) and from an individual not carrying the mutation (IWO). The cell lines were confirmed to be of B-cell origin by flow cytometry analysis. IWO cells interacted with E-selectin in an in vitro flow chamber analysis whereas SIGN cell did not. However, when SIGN cell was transiently transfected with wildtype FUT7 cDNA, interaction with E-selectin could be restored. Cell surface expression of the SLe(x)-related epitopes recognized by antibodies CSLEX-1, KM-93 and HECA-452 was elevated on IWO cells compared with that on SIGN cells, consistent with a role of these antigens in E-selectin recognition. These cell lines will be useful in further characterization of E-selectin ligands and encourage further studies on the consequences of the FUT7-G329A mutation in vivo.
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| 7. |
- Bokarewa, Maria, 1963, et al.
(author)
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Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy.
- 2007
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In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:4, s. 476-83
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty-six patients with established erosive RA non-responding to combination treatment with DMARDs and TNF-alpha inhibitors were treated with anti-CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin-producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12-58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow-up, B cells returned to circulation in 86% of patients. Fifty-three percent of the patients were successfully retreated with rituximab or re-started with anti-TNF-alpha treatment. Of the 11 non-responders, five were retreated with anti-CD20 within 2 months, four of them with success, four patients received TNF-alpha inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF-alpha inhibitors may be effectively treated with anti-CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities.
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| 8. |
- Bokarewa, Maria, 1963, et al.
(author)
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Pathological survivin expression links viral infections with pathogenesis of erosive rheumatoid arthritis.
- 2007
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In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:2-3, s. 192-8
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Research review (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage and bone destruction. Insufficient apoptosis in the inflamed RA synovium along with accumulation of highly differentiated B- and T-lymphocytes as well as invasive growth of macrophages and fibroblasts is among the major mechanisms supporting joint destruction. We have recently shown that circulating survivin, an apoptosis inhibitor tightly bound to tumorigenesis, is an independent predictor of development and progression of joint destruction in RA. In this review we discuss the possible connectivity between viral infection, leading to interferon (IFN)-alpha production, survivin expression, and subsequent joint inflammation. The role of IFN-alpha and the involvement of IFN transcription factors and phosphoinositide-3-kinase signalling as essential modulators of arthritogenic process are discussed in the context of survivin.
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| 9. |
- Bäckström, Fredrik, 1971, et al.
(author)
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Absence of in vitro responses to type II collagen by splenocytes from arthritic BALB/c mice is possibly caused by intrinsic CD25+ regulatory cells.
- 2008
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In: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:4, s. 362-9
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Journal article (peer-reviewed)abstract
- Collagen-induced arthritis-resistant BALB/c mice develop arthritis if a foreign protein is added to an emulsion of type II collagen (CII) and adjuvant. The IgG autoantibody activity to CII is increased, whereas no CII autoreactive T cells in vitro can be recorded. In this study, we have explored whether CD25+ cells inhibit T-cell autoreactivity to CII. We also followed the IgG anti-CII autoantibody activity and the IL-6 level in serum during the development of arthritis. BALB/c mice were coimmunized with bovine CII (BCII) and keyhole limpet haemocyanin (KLH) in complete Freund's adjuvant and boostered 3 weeks later. Control animals were immunized with either BCII or KLH. Sera were collected prior to and during the development of arthritis and examined for IgG anti-CII antibody activity and IL-6 content. When all BCII-KLH immunized mice had developed arthritis, splenocytes were prepared, with and without CD25+ cells, and tested for BCII reactivity in vitro. The serum IgG, IgG1 and IgG2a anti-CII antibody activities and the IL-6 level were significantly higher in BCII-KLH immunized mice than in BCII-immunized animals that failed to develop arthritis. The BCII-specific IL-2 secretion in vitro was significantly increased in CD25-depleted splenocyte cultures prepared from arthritic BCII-KLH-immunized mice. Development of arthritis in BALB/c mice induced by coimmunization with BCII/KLH results in increased levels of circulating IL-6 and IgG autoantibodies to CII. The arthritogenic BCII-KLH immunization potentiates BCII-specific IL-2 secretion by CD25-depleted splenocytes, but CD25+ cells hamper the outcome of their action, at least in vitro.
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| 10. |
- Bäckström, Fredrik, 1971, et al.
(author)
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Induction of experimental arthritis in BALB/c mice by inclusion of a foreign protein in the collagen inoculum
- 2008
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In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:4, s. 322-8
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Journal article (peer-reviewed)abstract
- The susceptibility of mice to collagen-induced arthritis (CIA) has, among other things, been linked to the major histocompatibility complex class II genes as well as other genes. This study was designed to examine the possibilities to establish CIA in low susceptible I-Ad (Balb/C) mice. Balb/C mice were immunized twice with bovine type II collagen (BCII) in complete Freund's adjuvant (CFA) containing the amount of Mycobacterium tuberculosis needed to induce CIA in low susceptible I-Ab (C57BL/6) mice. Some mice received the conceivable arthritogenic inoculum mixed with ovalbumin (OVA). Clinical arthritis was monitored. Antibody activity and T-cell reactivity to BCII were determined. Unexpectedly, only mice that were immunized with the BCII-OVA mixture developed arthritis. Combining BCII with another foreign protein, keyhole limpet hemocyanin, but not the self-protein mouse serum albumin, also triggered arthritis. Prior to the appearance of arthritis the serum levels of IgG autoantibodies to BCII were higher in the coimmunized mice than in the mice that were immunized with BCII alone. Yet, splenocytes stimulated in vitro with BCII did not proliferate or produce interferon-gamma. Immunization of Balb/c mice with an emulsion-containing CFA and BCII mixed with a foreign body, but not a self-protein, elevates the level of circulating autoantibodies to CII and subsequently induces arthritis.
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