| 1. |
- AbdGawad, Mohamed, et al.
(författare)
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Increased neutrophil membrane expression and plasma level of proteinase 3 in systemic vasculitis are not a consequence of the - 564 A/G promotor polymorphism.
- 2006
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 145:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Several findings link proteinase 3 (PR3) to small vessel vasculitis. Besides being a major target of anti-neutrophil cytoplasm antibodies (ANCA), previous findings have shown increased circulating levels of PR3 in vasculitis patients, increased levels of neutrophil membrane-PR3 (mPR3) expression and a skewed distribution of the − 564 A/G polymorphism in the promotor region of the PR3 gene. In this study we elucidate how these three findings relate to each other. The plasma concentration of PR3 was measured by enzyme-linked immunosorbent assay (ELISA), mPR3 expression by fluorescence activated cell sorter (FACS) and the gene polymorphism by real-time polymerase chain reaction (PCR). We compared results from 63 patients with ANCA-associated systemic vasculitis (AASV) with 107 healthy blood donors. In accordance with previous reports, AASV patients had increased plasma concentrations of PR3 compared to healthy controls (mean 224 µg/l versus 155 µg/l, P < 0·0001). They also showed an increased number of mPR3-positive neutrophils (60% versus 42%, P < 0·001). However, contrary to a previous report, we found no skewed distribution of the polymorphism in PR3 gene. There was a weak correlation between mPR3 mean fluorescence intensity (MFI) and plasma PR3 among healthy controls and myeloperoxidase–ANCA (MPO–ANCA)-positive patients (r = 0·24, P = 0·015 and r = 0·52, P = 0·011, respectively). In conclusion, increased plasma PR3 and high expression of mPR3 are associated with small vessel vasculitis, but neither of them is a consequence of the − 564 A/G polymorphism of the PR3 gene promotor.
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| 2. |
- Andersson, Anders, et al.
(författare)
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Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
- 2004
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
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| 3. |
- Andersson, S, et al.
(författare)
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Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau
- 2005
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 139:3, s. 483-489
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.
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| 4. |
- Hall, T. R., et al.
(författare)
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Longitudinal epitope analysis of insulin-binding antibodies in type 1 diabetes
- 2006
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 146:1, s. 41531-41531
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies to insulin (IAA) are one of the first markers of the autoimmune process leading to type 1 diabetes (T1D). While other autoantibodies in T1D have been studied extensively, relatively little is known about IAA and their binding specificities, especially after insulin treatment is initiated. We hypothesize that insulin antibodies (IA) that develop upon initiation of insulin treatment differ in their epitope specificities from IAA. We analysed insulin antibody binding specificities in longitudinal samples of T1D patients (n = 49). Samples were taken at clinical diagnosis of disease and after insulin treatment was initiated. The epitope specificities were analysed using recombinant Fab (rFab) derived from insulin-specific monoclonal antibodies AE9D6 and CG7C7. Binding of radiolabelled insulin by samples taken at onset of the disease was significantly reduced in the presence of rFab CG7C7 and AE9D6. rFab AE9D6 competed sera binding to insulin significantly better than rFab CG7C7 (P = 0.02). Binding to the AE9D6-defined epitope in the initial sample was correlated inversely with age at onset (P = 0.005). The binding to the AE9D6-defined epitope increased significantly (P < 0.0001) after 3 months of insulin treatment. Binding to the CG7C7-defined epitope did not change during the analysed period of 12 months. We conclude that epitopes recognized by insulin binding antibodies can be identified using monoclonal insulin-specific rFab as competitors. Using this approach we observed that insulin treatment is accompanied by a change in epitope specificities in the emerging IA.
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| 5. |
- Hillman, Magnus, et al.
(författare)
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The glutamic acid decarboxylase 65 immunoglobulin G subclass profile differs between adult-onset type 1 diabetes and latent autoimmune diabetes in adults (LADA) up to 3 years after clinical onset.
- 2009
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 157:2, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against glutamic acid decarboxylase 65 (GADA) are found frequently in patients with autoimmune diabetes. Immunoglobulin (Ig)G(1) is the most frequent subclass among the GADA IgG subclasses. IgG(4) is a more common subclass in latent autoimmune diabetes in adults (LADA) at clinical onset compared to type 1 diabetes. The aim of this work was to study the different GADA-IgG subclass profiles during a 3-year follow-up in these groups of autoimmune diabetes. Adult-onset subjects, classified as either type 1 (n = 40) or LADA (n = 43), were included in the study. New samples were collected every year from these patients. In addition to conventional GADA analyses, GADA-IgG subclasses were also analysed with a radioimmunoprecipitation assay using biotin-conjugated antibodies (directed against human IgG subclasses and IgM) and streptavidin Sepharose. During 3 years' follow-up, all the IgG subclass levels decreased in type 1 diabetes - IgG(1): P < 0.001; IgG(2): P < 0.001; IgG(3): P < 0.001; IgG(4): P < 0.05 (Friedman's' test) - while levels remained stable for all four subclasses in LADA. GADA IgM, however, decreased in both groups (P < 0.001). Patients with LADA have higher GADA IgG(3) and IgG(4) at clinical onset and seem to maintain the levels and profile of their IgG subclasses up to 3 years after clinical onset, while all the GADA IgG subclass levels decrease in type 1 diabetic patients. This indicates a persistent different immune response in LADA compared to type 1 diabetes and further indicates the difference in pathogenesis.
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| 6. |
- Jonson, Carl-Oscar, et al.
(författare)
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Regulatory T-cell associated activity in Photopheresis-induced Immune tolerance in Recent Onset Type 1 Diabetes Children
- 2008
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 153:2, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-β are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD65) peptide a.a. 247–279. CTLA-4, sCTLA-4, FoxP3 and TGF-β mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P < 0·05) but decreased in expression after stimulation with GAD65-peptide (P < 0·05) and PHA (P < 0·05). Spontaneous TGF-β (P < 0·05) increased whereas PHA- (P < 0·01) and GAD65-peptide (P < 0·01)-induced TGF-β expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-β, stimulated with PHA and GAD65 peptide, decreased with time, with a parallel reduction of GAD65-peptide and PHA-stimulated TGF-β expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D.
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| 7. |
- Mölne, L, et al.
(författare)
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Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused by Staphylococcus aureus.
- 2003
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 132:2, s. 209-215
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Tidskriftsartikel (refereegranskat)abstract
- The high number of /-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of / T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking /-expressing T cells (TCR/) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCR+/ control mice. The number of bacteria recovered from the skin of TCR/ mice was significantly higher (P = 0·0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCR+/ congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCR/ mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the /-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread.
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| 8. |
- Nilsson, Rune, et al.
(författare)
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Extracorporeal immunoadsorption therapy on rats. In vivo depletion of specific antibodies
- 1990
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 82:3, s. 440-444
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Tidskriftsartikel (refereegranskat)abstract
- A technique for extracorporeal immunoadsorption of circulating specific antibodies from the plasma of rats is described. Catheterization of rats was performed using the carotid and the jugular blood vessels. The rats were treated non-anaesthetized. Blood was pumped continuously through a hollow-fibre plasma filter at a rate of 1.5 ml/min and plasma was separated and passed through an adsorbent column at a flow of 0.2 ml/min. The treated plasma was mixed with the blood cells before being returned to the rat. The column contained the antigen covalently linked to agarose beads. About three plasma volumes were treated during a period of 3 h and 30 min, which resulted in an antibody depletion of about 90-95%. The antibody levels returned to pre-adsorption levels after 4-5 days, or in some cases even exceeded the titres before treatment.
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| 9. |
- Silver, Christina, et al.
(författare)
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Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency.
- 2010
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; May 4, s. 48-56
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Tidskriftsartikel (refereegranskat)abstract
- Summary Approximately 10% of the patients diagnosed with type 2 diabetes (T2D) have detectable serum levels of glutamic acid decarboxylase 65 autoantibodies (GADA). These patients usually progress to insulin dependency within a few years, and are classified as being latent autoimmune diabetes in adults (LADA). A decrease in the frequency of peripheral blood natural killer (NK) cells has been reported recently in recent-onset T1D and in high-risk individuals prior to the clinical onset. As NK cells in LADA patients have been investigated scarcely, the aim of this study was to use multicolour flow cytometry to define possible deficiencies or abnormalities in the frequency or activation state of NK cells in LADA patients prior to insulin dependency. All patients were GADA-positive and metabolically compensated, but none were insulin-dependent at the time blood samples were taken. LADA patients exhibited a significant decrease in NK cell frequency in peripheral blood compared to healthy individuals (P = 0.0018), as reported previously for recent-onset T1D patients. Interestingly, NKG2D expression was increased significantly (P < 0.0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P < 0.0001) within the NK cell population. These observations highlight a defect in both frequency and activation status of NK cells in LADA patients and suggest that this immunological alteration may contribute to the development of autoimmune diabetes by affecting peripheral tolerance. Indeed, recent evidence has demonstrated a regulatory function for NK cells in autoimmunity. Moreover, the decrease in NK cell number concords with observations obtained in recent-onset T1D, implying that similar immunological dysfunctions may contribute to the progression of both LADA and T1D.
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| 10. |
- Segelmark, Mårten, et al.
(författare)
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Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin?
- 1997
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 108:1, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO, in vivo. We also speculate that impaired inactivation of MPO may have a pathophysiological role in inflammatory diseases characterized by autoantibodies to MPO, such as rapidly progressive glomerulonephritis with P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies).
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