| 1. |
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| 2. |
- Rüdhmer-Dahle, Charlotte, 1956-
(författare)
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Studies on T cells and cytokines in Guillain-Barré syndrome and experimental allergic neuritis
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Guillain-Barrésyndrome (GBS) is an inflammatory disease of peripheral nerves, characterised by muscle weakness. The nerves are attacked and destroyed by the immune system. The symptoms usually progress over a few weeks and many patients become severely disabled. However, in contrast to many other organspecific autoimmune diseases, GBS is self-limiting and most patients recover. Individuals of all ages can be affected. The incidence is about 1/100 000 per year. An infection often precedes the onset of neurological symptoms and probably triggers the immune-mediated attack.Activation of T cells and the resulting release of cytokines are decisive for the regulation of antigen-specific inflammation. Different cytokine patterns promote different types of responses. Interferon-y (lFN-γ) has a key role in Th type 1 responses, and is thought to be a driving force in many organ-specific autoimmune diseases. Interleukin-4 (IL-4) promotes Th type 2 responses, characterised by the production of certain antibodies and activation of mastcells and eosinophils. Th type 1 and Th type 2 responses down-regulate one another and the balance between them is important for the immune homeostasis. TGF-ß is an important cytokine with strong down-regulatory properties.Flow cytometry studies showed that circulating T cells were activated in patients with GBS as determined by expression of HLA-DR on T cells, increased proportion of activated memory phenotype (CD4+CD29+), and decreased proportion of naive phenotype (CD4+CD45RA+). A sensitive Ell-spot method was used to determine cytokine secretion from circulating mononuclear cells with or without stimulation with immunogenic peptides from myelin proteins P2 and PO. Both spontaneous and myelin-specific cytokine secretion were increased in patients compared with controls. Increased numbers of myelin-specific cells secreting IL-4 and TGF-ß were found in the majority of the patients, indicating a Th2 type and down-regulatory cytokine profile, in line with the self-limiting character of the disease.An animal model of GBS, experimental allergic neuritis (EAN), is known to be inducible by myelin-specific T cells, supporting the pathogenetic role of T cells. A Th1 deviated, IFN-y-producing cell population from EAN, was in vitro stimulated with autoantigen and IL-4, thereby obtaining a Th2 cytokine profile. These myelin-specific cells were subsequently transferred to rats with EAN, and were found to ameliorate the disease course.In conclusion, Circulating T cells are activated in patients with GBS. Most patients have myelin-specific T cells that mainly secrete down-regulatory cytokines such as IL-4 and TGF-ß, which probably have a beneficial role in regulating the disease process. In vitro deviation of myelin-specific T cells into Th2 phenotype and subsequent transfer of these cells ameliorated the disease course in EAN.
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| 3. |
- Backteman, K, et al.
(författare)
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A rapid and reliable flow cytometric routine method for counting leucocytes in leucocyte-depleted platelet concentrates
- 2002
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 83:1, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: To ensure a proper quality control it is important to use a reliable method to count low numbers of leucocytes in leucocyte-reduced platelet concentrates (PCs). Materials and Methods: A modified flow cytometric method for counting low numbers of leucocytes, based on a reference population contained in tubes with an exact number of fluorescent beads and staining with propidium iodide was used. To increase the number of events, the original sample volume was increased. Results: There was a good correlation in the number of leucocytes (r = 0.99) between the modified flow cytometric method and microscopy of samples from unfiltered and expected numbers from serially diluted PCs. Samples from leucocyte-reduced PCs obtained by apheresis or filtered buffy coats showed no correlation between results from the modified flow cytometric method and microscopy (Nageotte). Conclusion: Counting by microscopy gave a lower number of leucocytes than the modified flow cytometric method when counting a low number of cells. However, analysis of the serially diluted PCs proved that the modified flow cytometric method was reliable and rapid, making it suitable for clinical routine use.
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| 4. |
- Dahle, Charlotte, et al.
(författare)
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Elevated number of cells secreting transforming growth factor β in Guillain-Barré syndrome
- 2003
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 111:12, s. 1095-1104
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Tidskriftsartikel (refereegranskat)abstract
- We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-γ, TGF-β, IL-6, and TNF-α by circulating mononuclear cells during the course of Guillain-Barré syndrome (GBS). Compared to healthy controls, patients with GBS had higher numbers of TGF-β-secreting cells and the number of individuals with myelin-peptide-induced IL-4 and TGF-β secretion was higher in the GBS group. No significant differences were seen concerning the predominantly pro-inflammatory cytokines IFN-γ, IL-6 or TNF-α. Our findings indicate a down-regulatory role for TGF-β and IL-4 in GBS.
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| 5. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Antibodies and T-cell reactivity to Borrelia burgdorferi in an asymptomatic population : A study of healthy blood donors in an Inland town district in the South-East of Sweden
- 2001
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 33:11, s. 806-808
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Tidskriftsartikel (refereegranskat)abstract
- To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-? ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.
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| 6. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Detection of spontaneous and antigen-induced human interleukin-4 responses in vitro : Comparison of ELISPOT, a novel ELISA and real-time RT-PCR
- 2002
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Ingår i: JIM - Journal of Immunological Methods. - 0022-1759 .- 1872-7905. ; 260:1-2, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-4 (IL-4) is an important T-helper cell type 2 (Th2) cytokine in man, driving Th2 polarisation and exerting the most antagonistic effects to the Th1 cytokine interferon-? (IFN-?). Nevertheless, few data on spontaneous and antigen-specific secretion of IL-4 in man are available, mainly due to difficulties in the detection of IL-4. In this study, we compared three assays that can detect antigen-induced IL-4 responses, ELISPOT, ELISA after blocking the IL-4 receptor during cell culture, and real-time reverse transcription polymerase chain reaction (RT-PCR). Spontaneous, antigen- and allergen-induced responses were analysed in peripheral blood mononuclear cells from three groups with different secretion patterns for IL-4: atopic individuals, nonatopic individuals and pregnant women. ELISPOT displayed the highest sensitivity and was the only assay that could detect spontaneous secretion of IL-4 in all analysed samples. The IL-4 receptor blocking ELISA was considered best for the detection of in vitro antigen- and allergen-induced responses, since the results obtained from the ELISPOT and real-time RT-PCR displayed lower specificity, possibly because of seemingly aberrant IL-4 responses in the group of pregnant women. The real-time RT-PCR for detection of IL-4 mRNA proved to be sensitive, but expression of IL-4 mRNA was not correlated with the secretion of IL-4.
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| 7. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Lyme borreliosis in Sweden - Diagnostic performance of five commercial Borrelia serology kits using sera from well-defined patient groups
- 2004
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 112:1, s. 74-78
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Tidskriftsartikel (refereegranskat)abstract
- Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.
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| 8. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis
- 2003
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 145:1-2, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.
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| 9. |
- Ekerfelt, Christina, et al.
(författare)
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Spontaneous secretion of interleukin-4, interleukin-10 and interferon-gamma by first trimester decidual mononuclear cells
- 2002
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Ingår i: American Journal of reproductive immunology. - : Wiley. - 8755-8920 .- 1046-7408. ; 47:3, s. 159-166
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: A T-helper cell type 2 (Th2) cytokine dominated microenvironment has been predicted to be crucial for successful pregnancy. However, little information is available about local cytokine secretion in the human decidua. We determined the spontaneous secretion of interleukin-4 (IL-4), interferon-γ (IFN-γ) and IL-10 by decidual mononuclear cells at the single cell level and compared it with their secretion by peripheral blood mononuclear cells (PBMC) in the first trimester of pregnancy. METHODS OF STUDY: The cytokine secretion from decidual and blood cells was detected by a sensitive enzyme-linked immunosorbent spot-forming cell (ELISPOT)-assay. RESULTS: Cells secreting IL-4 (median 153, range 8–530), IL-10 (median 188, range 32–1600) and IFN-γ (median 123, range 15–1140) were detected in all decidual and blood samples. The cytokine secretion showed a co-linear pattern in both the blood and decidua, i.e. when one cytokine was secreted at high levels, the others followed the trend. No correlation was found between the number of cytokine secreting cells in blood and decidua for any of the cytokines. CONCLUSIONS: Interleukin-4 and IL-10 are locally secreted in the decidua early during normal pregnancy, probably counteracting the fetal rejecting effects of co-expressed IFN-γ. The cytokine secretion by blood cells does not generally reflect the local secretion pattern during first trimester pregnancy.
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| 10. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis
- 2001
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 123:1, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way.
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| 11. |
- Eriksson, Per, 1958-, et al.
(författare)
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Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls
- 2004
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:3, s. 617-620
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0.52, P = 0.0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.
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| 12. |
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| 13. |
- Ernerudh, Jan, 1952-, et al.
(författare)
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Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes
- 2004
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Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 11:5, s. 856-861
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Tidskriftsartikel (refereegranskat)abstract
- In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4 +CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 +) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.
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| 14. |
- Ernerudh, Jan, 1952-, et al.
(författare)
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The use of cell products for treatment of autoimmune neuroinflammatory diseases
- 2002
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Ingår i: Current Medicinal Chemistry. - 0929-8673 .- 1875-533X. ; 9:16, s. 1497-1505
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Tidskriftsartikel (refereegranskat)abstract
- Cell products are live cells that are given to patients in order to replace or modify the function of missing or dysfunctional cells. Progress in technology and in the understanding of pathobiology may lead to the use of cell products in many areas. This review outlines the use of cell products in the treatment of autoimmune diseases, with focus on neuroinflammatory diseases like multiple sclerosis. Treatment of autoimmune diseases should be selective and specific in order to avoid serious side effects. To achieve this, T lymphocyte regulation has been in focus for several immunomodulatory regimens. One area of great interest is the use of T cell vaccination, when autologous attenuated auto-reactive T cells are given to patients in order to initiate a specific immune response to the pathogenic T cell populations. Phopheresis may be an immunomudulatory treatment related to T cell vaccination. Another promising area involves ex-vivo alteration of the cytokine profile of harmful auto-reactive T cells. This can be achieved by genetic manipulation or by certain cytokine stimulations. A subsequent adoptive cell transfer will, by homing mechanisms, lead to at site specific delivery of the cells, which will have a local down-regulatory effect on the inflammatory process. Although unsolved questions regarding doses, timing, optimal preparing conditions and mechanisms still remain, both T cell vaccination and adoptive transfer of ex-vivo manipulated cytokine secreting cells have proven successful for treatment of neuroinflammation in experimental models. T cell vaccination was shown to be feasible in patients with multiple sclerosis, however, otherwise the experience in humans so far is limited.
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| 15. |
- Esamai, Fabian, et al.
(författare)
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Cerebral malaria in children : Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome
- 2003
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Ingår i: Journal of Tropical Pediatrics. - : Oxford University Press (OUP). - 0142-6338 .- 1465-3664. ; 49:4, s. 216-223
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Tidskriftsartikel (refereegranskat)abstract
- This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty‐three children admitted to the hospital with cerebral (CM) and 10 children with noncerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF‐α) and transforming growth factor (TGF‐β1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF‐β1 and TNF‐α decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF‐α and TGF‐β1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF‐β and higher levels of TNF‐α than those in lighter levels of coma. The serum TNF‐α levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF‐α and higher levels of TGF‐β than those with a longer duration of illness before admission. In conclusion, this study shows that TNF‐α and TGF‐β1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF‐α and TGF‐β levels were inversely related both in serum and CSF.
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| 16. |
- Faresjö, Maria, 1971-, et al.
(författare)
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Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes
- 2004
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 59:5, s. 517-526
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the β cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-γ, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD65)-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD 65-peptide caused an increased ratio of IFN-γ/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-γ (P = 0.07). Expression of IFN-γ mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.
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| 17. |
- Forsey, R.J., et al.
(författare)
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Plasma cytokine profiles in elderly humans
- 2003
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Ingår i: Mechanisms of Ageing and Development. - 0047-6374 .- 1872-6216. ; 124:4, s. 487-493
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-ß levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 18. |
- Jablonowska, Barbara, 1948-, et al.
(författare)
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Blocking antibodies in blood from patients with recurrent spontaneous abortion in relation to pregnancy outcome and intravenous immunoglobulin treatment
- 2001
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897 .- 8755-8920. ; 45:4, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect.METHOD OF STUDY: Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, pre-pregnancy blood samples from 31 RSA women and 10 controls were obtained.RESULTS: We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment.CONCLUSIONS: Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.
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| 19. |
- Jablonowska, Barbara, 1948-, et al.
(författare)
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T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion : IVIG versus placebo treatment
- 2002
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Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 48:5, s. 312-318
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Tidskriftsartikel (refereegranskat)abstract
- Jablonowska B, Palfi M, Matthiesen L, Selbing A, Kjellberg S, Ernerudh J. T and B Lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment. AJRI 2002; 48:312–318 © Blackwell Munksgaard, 2002PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG).METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry.RESULTS: The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group.CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.
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| 20. |
- Jansson, A., et al.
(författare)
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Elispot assay detection of cytokine secretion in multiple sclerosis patients treated with interferon-β1a or glatiramer acetate compared with untreated patients
- 2003
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 9:5, s. 440-445
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind the beneficial effects of interferon-β1a (IFN-β1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. Altered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-γ (IFN-γ) and enhancement of anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-β1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG)-14-39 and MOG 63-87) IFN-γ, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-γ, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-γ and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-β1a treated group. Thus, immunological effects of IFN-β1a and GA were similar showing that disease promoting Th1 (IFN-γ) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.
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| 21. |
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| 22. |
- Jonsson, Yvonne, et al.
(författare)
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Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia: no differences compared with normal pregnancy
- 2004
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Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 51:4, s. 302-310
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Tidskriftsartikel (refereegranskat)abstract
- Problem: A Th1-shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high-sensitivity technique for cytokine detection.Methods of study: Spontaneous as well as 'fetus-specific' and recall antigen-specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon-γ, interleukin (IL)-4, IL-10 and IL-12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). Fetus-specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay.Results: All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine-secreting cells were found between the two groups.Conclusions: No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.
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| 23. |
- Kvarnström, Maria, 1971-, et al.
(författare)
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Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)
- 2002
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 127:2, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-λ type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.
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| 24. |
- Lidström Gustafsson, Charlotte, et al.
(författare)
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Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood : Implications for suppressor macrophages in decidua
- 2003
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Ingår i: American Journal of reproductive immunology. - : Wiley. - 8755-8920 .- 1046-7408 .- 1600-0897. ; 50:6, s. 444-452
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Tidskriftsartikel (refereegranskat)abstract
- Problem: Local immune modulation has been shown to be of considerable importance for the maintenance of successful pregnancy. We have previously reported the secretion of interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-10 in human decidua from early normal pregnancy. The aim of this study was to investigate the cellular source of cytokine secretion in the decidua, and compare this to secretion patterns in peripheral blood. Method of study: Decidual tissue and peripheral blood was collected from 20 women undergoing surgical abortion during first trimester pregnancy. Monocytes/macrophages and NK cells were enriched by immunomagnetic cell separation and cytokine secretion was detected by enzyme-linked immunosorbent spot-forming cell assay. Results: Decidual and peripheral monocytes/macrophages and NK cells spontaneously secrete IFN-γ, IL-4 and IL-10. The number of IL-10 secreting cells was significantly higher in decidual macrophages compared with decidual non-monocytic cells as well as compared with blood monocytes/macrophages. These differences were not seen for IFN-γ or IL-4. Conclusions: Our results indicate that decidual macrophages subserve important suppressive functions in the pregnant uterus.
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| 25. |
- Lindvall, Björn, 1952-, et al.
(författare)
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Subclinical myositis is common in primary Sjögren's syndrome and is not related to muscle pain
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 29:4, s. 717-725
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although muscle pain is common in primary Sjögren's syndrome (SS), the underlying mechanisms are mainly unknown. We studied all patients with SS at our rheumatology unit with respect to muscle pain in general and to fibromyalgia (FM), and correlated clinical data to muscle biopsy findings.METHODS: We investigated 48 patients with SS according to the modified European diagnostic criteria. The ACR criteria for FM were used to subgroup the patients. Muscle biopsy was performed in 36 patients. Light microscope morphology and immunohistochemical expression of MHC class I, MHC class II, and membrane attack complex (MAC) were studied.RESULTS: We found 44% of patients complained of muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms of myalgia. Muscle pain could not be related to histopathological findings. Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined with degeneration/regeneration (i.e., histological signs of polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical as well as histological signs of polymyositis. Eight muscle biopsies (22%) showed histological features of inclusion body myositis (IBM). However, no patient had clinical symptoms suggestive of this disease. Abnormal expression of MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients, respectively.CONCLUSION: Muscle pain, especially FM, is common in SS. Histopathological signs of myositis are very common in SS. However, muscle symptoms are not related to histological signs of muscle inflammation. IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.
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