| 1. |
- Agostoni, Angelo, et al.
(författare)
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Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond
- 2004
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 114:3 Suppl, s. 51-131
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.
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| 2. |
- Alper, CA, et al.
(författare)
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Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency
- 2003
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Ingår i: Journal of Clinical Immunology. - 0271-9142. ; 23:4, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- About 25% of C2-deficient homozygotes have increased susceptibility to severe bacterial infections. C2-deficient homozygotes had significantly lower serum levels of IgG2, IgG4, IgD, and Factor B, significantly higher levels of IgA and IgG3 and levels of IgG1 and IgM similar to controls. Type I ( 28 bp deletion in C2 exon 6 on the [HLA-B18, S042, DR2] haplotype or its fragments) and type II ( non-type I) C2-deficient patients with increased susceptibility to bacterial infection had significantly lower mean levels of IgG4 ( p < 0.04) and IgA ( p < 0.01) than those without infections ( who had a higher than normal mean IgA level) but similar mean levels of other immunoglobulins and Factor B. Of 13 C2-deficient homozygotes with infections, 85% had IgG4 deficiency, compared with 64% of 25 without infections. IgD deficiency was equally extraordinarily common among infection-prone (50%) and noninfection-prone (70%) homozygous type I C2-deficient patients. IgD deficiency was also common (35%) among 31 type I C2-deficient heterozygotes ( with normal or type II haplotypes), but was not found in 5 type II C2-deficient heterozygotes or 1 homozygote. Thus, C2 deficiency itself is associated with many abnormalities in serum immunoglobulin levels, some of which, such as in IgG4 and IgA, may contribute to increased susceptibility to infection. In contrast, IgD deficiency appears not to contribute to increased infections and appears to be a dominant trait determined by a gene or genes on the extended major histocompatibility complex (MHC) haplotype [HLA-B18, S042, DR2] ( but probably not on type II C2-deficient haplotypes) similar to those previously identified on [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3].
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| 3. |
- Bengtsson, Anders, et al.
(författare)
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Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
- 2000
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 9:9, s. 664-671
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.
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| 4. |
- Börjesson, Anna, et al.
(författare)
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Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats.
- 2002
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Ingår i: Digestive and Liver Disease. - 1590-8658. ; 34:3, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intestinal ischaemia-reperfusion can lead to pulmonary injury characterised by increased macromolecular leakage and leukocyte sequestration. Important mediators of ischaemia-reperfusion-associated injury include polymorphonuclear granulocytes and platelet-activating factor. AIM: To investigate the potential therapeutic inhibition of platelet-activating factor in intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent platelet-activating factor-receptor antagonist, lexipafant. METHODS: Rats were subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes reperfusion. RESULTS: Increased leakage of radiolabelled human serum albumin was found in the lungs after intestinal ischaemia followed by 3 or 12 hours reperfusion. Administration of lexipafant did not significantly prevent the increased leakage. Pulmonary myeloperoxidase content increased after intestinal ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration through the pulmonary endothelium. The increase in interleukin-1beta seen after 3 hours reperfusion was partly reversed by lexipafant. CONCLUSIONS: Pulmonary injury occurred following intestinal ischaemia-reperfusion, characterised by increased leakage of radiolabelled albumin over the endothelial barrier; correlating with increased pulmonary myeloperoxidase-content, implying involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly decrease severity of pulmonary damage.
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| 5. |
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| 6. |
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| 7. |
- Danielsson, Gudmundur, et al.
(författare)
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Flavonoid treatment in patients with healed venous ulcer: flow cytometry analysis suggests increased CD11b expression on neutrophil granulocytes in the circulation
- 2003
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Ingår i: Vascular Medicine. - : SAGE Publications. - 1477-0377 .- 1358-863X. ; 8:2, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to determine the activation of white blood cells (WBCs) and endothelial cells in patients with healed venous ulcer and the influence of the standing position and of treatment with flavonoids. Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days. Blood samples were taken from arm and dorsal foot veins before and after standing for 30 minutes. Blood sampling was performed before treatment, after three days, one month and three months. The activation of WBCs was determined by measuring adhesion molecule CD11b and CD18 expression on the surface of granulocytes and monocytes. In addition, interleukin 6 (IL-6), IL-8, soluble E-selectin (sE-selectin), sL-selectin and sICAM-1 levels in serum were quantified. The results showed that standing did not influence any of the measured parameters significantly. Expression of CD11b adhesion molecules on granulocytes was significantly up-regulated (p=0.044) after treatment with flavonoids for one month, but this increase was not significant (p=0.056) two months after the treatment period compared with the baseline level. The expression of CD18 remained unchanged. Baseline expression of CD11b or CD18 on monocytes did not change significantly during the study period. Neither was any significant change observed in the levels of IL-6, IL-8 or the soluble adhesion molecules. It was concluded that flavonoid treatment for 30 days increased the expression of CD11b adhesion molecules on circulating granulocytes. No general effect on the inflammatory process could be observed as assessed by levels of cytokines and soluble adhesion molecules. Possible explanations for these findings could be that a decreased number of primed granulocytes leave the circulation due to a changed WBC/endothelial cell interaction or that flavonoids have a direct effect on granulocytes. Further studies are needed to clarify the mode of action of flavonoids in chronic venous disease.
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| 8. |
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| 9. |
- Jaatinen, Taina, et al.
(författare)
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Total C4B deficiency due to gene deletion and gene conversion in a patient with severe infections
- 2003
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Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 10:2, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Deficiencies of the early components of the classical complement pathway impair the actions of innate and humoral immunity and may lead to increased susceptibility to infections. We have studied the genetic basis of total C4B deficiency in a Finnish patient with recurrent meningitis, chronic fistulas and abscesses. The maternal chromosome carried a four-gene deletion including the C4B gene, and a conversion from C4B to C4A gene was found on the paternal chromosome resulting in complete deficiency of C4B. In the converted C4A gene, mutation screening did not reveal any amino acid changes or prominent mutations, yet a large number of nucleotide variations were found. Further, the patient was heterozygous for structural deficiency of mannan binding lectin (MBL) associating with medium levels of serum MBL. Our data provides new information on the genetic instability of the C4 gene region, and on the association of homozygous C4B deficiency and variant MBL genotype with increased susceptibility to recurrent and chronic infections. Importantly, plasma therapy induced a prompt clinical cure with long-term effects.
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| 10. |
- Jansson, Kjell, 1958-, et al.
(författare)
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Intraperitoneal cytokine response after major surgery : higher postoperative intraperitoneal versus systemic cytokine levels suggest the gastrointestinal tract as the major source of the postoperative inflammatory reaction
- 2004
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Ingår i: American Journal of Surgery. - : Elsevier BV. - 0002-9610 .- 1879-1883. ; 187:3, s. 372-377
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytokine response is an important factor in the development of shock and organ failure. The aim of this study was to investigate intraperitoneal (peritoneal) and venous (systemic) postoperative cytokine release after major surgery.METHODS: Major abdominal surgery was performed in 19 patients. Preoperative systemic measurements and postoperative systemic and peritoneal measurements of C-reactive protein (CRP) and the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-6), and IL-10 were performed.RESULTS: Significantly higher TNF-alpha, IL-6, and IL-10 peritoneal values were recorded compared with systemic values, whereas peritoneal CRP was significantly decreased. CRP increased significantly over time, whereas postoperative values of IL-6, IL-10, and peritoneal TNF-alpha decreased. Systemic TNF-alpha was constant over time, but values after emergent abdominal surgery showed a more extensive response. An additional effect of surgery and emergent abdominal disease was seen in increased TNF-alpha and IL-10 levels.CONCLUSIONS: Compared with systemic cytokines, peritoneal cytokines respond extensively after major surgery, indicating that measurement of peritoneal cytokines is a more sensible method to determine postoperative inflammatory reaction. A normal postoperative course is characterized by decreasing levels of peritoneal cytokines.
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