Biomedical subjects

K Selleng

Publications and source records attributed to K Selleng.

4 recordsLinked to original sources

PubMed2001

Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.

OBJECTIVE: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT). BACKGROUND: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery. METHODS: We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA. RESULTS: HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes. CONCLUSIONS: In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.

Antibody Specificity↗

PubMed2001

Increased expression of CTLA-4 (CD152) by T and B lymphocytes in Wegener's granulomatosis.

CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Furthermore, CTLA-4 has a role in inducing a Th1 response and suppressing Th2 cytokines, an effect which is antagonized by CD28. Many autoimmune diseases are characterized by an overwhelming production of Th1 cytokines. Recently, the predominance of the Th1 cytokine pattern has been directly observed in the granulomatous inflammation of patients with Wegener's granulomatosis. The balance between CD28 and CTLA-4 expression by T lymphocytes could be a factor in the pathogenesis of autoimmune diseases. Down regulation of CD28 predominantly on CD8+ T cells has been described in Wegner's granulomatosis; however, analysis of CTLA-4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA-4 on PBMC in patients with Wegener's granulomatosis (n = 25) in comparison with healthy controls (n = 19). Expression levels of CTLA-4 were significantly increased selectively on CD4+ and possibly also on CD4-/CD8- T cells in Wegener's granulomatosis. High CTLA-4 expression by T lymphocytes was associated with more severe disease. In contrast, after stimulation with the mitogen PHA, CTLA-4 levels were strongly increased on T cells from controls but in T cells from Wegener's granulomatosis patients this response was severely impaired. Interestingly, while CTLA-4 was seen exclusively on T cells in control individuals, about half of the Wegener's patients showed CTLA-4 expression by a fraction of peripheral B lymphocytes. CTLA-4 positive B cells in the periphery were associated with less acute disease.

Abatacept↗

PubMed1999

Isolation of highly enriched human monocytes from ten ml samples of heparinised whole blood.

A detailed study of the immune dysregulation involved in systemic inflammation requires the analysis of the main inflammatory cells in the circulation - the monocytes. Blood samples available from patients are necessarily restricted so that a rapid and efficient method is required to isolate these cells. Here we present a protocol to isolate blood monocytes in high yield from small samples of heparinised blood. The method yields monocyte preparations with a purity greater than 96%.

Cell Separation↗

PubMed1999

Gene expression pattern in human monocytes as a surrogate marker for systemic inflammatory response syndrome (SIRS).

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a mild inflammatory episode which, in a minority of patients, may deteriorate into septic shock. In the mouse, injection of bacteria or bacterial endotoxin induces systemic inflammation through the activation of blood monocytes, which leads to lethal shock. A number of intervention strategies have been shown to prevent progression to shock in mouse model systems. However, recent clinical trials of a number of these therapeutic strategies in patients have been uniformly disappointing. In contrast to the situation in the mouse models, there may be many different ways to initiate systemic inflammation in patients and not all of them need necessarily involve activation of blood monocytes. If there is no unifying mechanism behind the induction of systemic inflammation in patients and no common rules governing its development, then it is unlikely that generally applicable therapeutic strategies will be found that can prevent progression into shock. MATERIALS AND METHODS: We used differential display to compare gene expression patterns in monocytes of recent-admission multi-trauma patients with clinically diagnosed SIRS to the patterns in monocytes of healthy controls. RESULTS: Of seven differentially displayed bands that were recovered and sequenced, five were associated with SIRS and two were preferentially expressed in the monocytes of healthy controls. CONCLUSION: The data show that monocytes of SIRS patients are in an activation state that is different from that of monocytes from the healthy controls, that monocytes from many individual patients share similar patterns of differentially expressed sequences, and that by this criterion, the multi-trauma SIRS patients are a remarkably coherent group.

Adolescent↗