False homozygous HLA genotyping results due to copy number neutral loss of heterozygosity in acquired aplastic anaemia.

The aim of this case report is to draw attention on possible false human leucocyte antigen (HLA) genotyping in acquired aplastic anaemia prior to allogeneic haematopoietic stem cell transplantation. In acquired aplastic anaemia loss of heterozygosity (LOH) of chromosome 6p is known to occur in around 12%. We report false HLA genotyping results due to LOH and a coinciding steep rise in neutrophils following filgrastim stimulation in a patient with very severe aplastic anaemia.

Predictive factors of allosensitization after immunosuppressant withdrawal in recipients of long-term cultured islet cell grafts.

Background: Islet transplantation has been reported to induce allosensitization in the majority of type 1 diabetic recipients of fresh or shortly incubated islet grafts prepared from one to three donors.

Methods: We examined the appearance of human leukocyte antigen (HLA) antibodies after withdrawal of immunosuppressants in 35 type 1 diabetic recipients of islet cell grafts prepared from a median of 6 donors (range, 2-11), cultured for longer periods, and characterized for their cellular composition. Immunosuppression consisted of antithymocyte globulin induction followed by mycophenolate mofetil plus calcineurin inhibitors (n=28, with 7 also receiving steroids) or sirolimus with (n=3) or without calcineurin inhibitors (n=4).

Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission.

Killer immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA mismatched hematopoietic stem cell transplants induce alloreactive NK cells, which prevent leukemia relapse. Certain KIR/HLA combinations protect against HIV-1 infection, but the effect of KIR/HLA mismatches between sexual partners has never been investigated.

Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.

Background: Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance.

Immunomodulatory effect of NSAID in geriatric patients with acute infection: effects of piroxicam on chemokine/cytokine secretion patterns and levels of heat shock proteins. A double-blind randomized controlled trial. (ISRCTN58517443).

Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection.

Circulating heat shock protein 70 in health, aging and disease.

Background: Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context.

Low CD4+ T cell counts among African HIV-1 infected subjects with group B KIR haplotypes in the absence of specific inhibitory KIR ligands.

Natural killer (NK) cells are regulated by interactions between polymorphic killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA). Genotypic combinations of KIR3DS1/L1 and HLA Bw4-80I were previously shown to influence HIV-1 disease progression, however other KIR genes have not been well studied. In this study, we analyzed the influence of all activating and inhibitory KIR, in association with the known HLA inhibitory KIR ligands, on markers of disease progression in a West African population of therapy-naïve HIV-1 infected subjects.

Role of the inhibitory KIR ligand HLA-Bw4 and HLA-C expression levels in the recognition of leukemic cells by Natural Killer cells.

Transplantation of acute myeloid leukemia (AML) patients with grafts from related haploidentical donors has been shown to result in a potent graft-versus-leukemia effect. This effect is mediated by NK cells because of the lack of activation of inhibitory killer cell immunoglobulin-like receptors (KIRs) which recognize HLA-Bw4 and HLA-C alleles. However, conflicting results have been reported about the impact of KIR ligand mismatching on the outcome of unrelated HLA-mismatched hematopoietic stem cells transplants (HSCT) to leukemic patients.

Aging-related differences in basal heat shock protein 70 levels in lymphocytes are linked to altered frequencies of lymphocyte subsets.

Cell stress responses are ubiquitous in all organisms and are characterized by the induced synthesis of heat shock proteins (Hsp). Previous studies as well as recent reports by our group have consistently suggested that aging leads to an increase in the basal levels of Hsp70. Here we extend these studies by examining the differential Hsp70 response of peripheral blood lymphocyte (PBL) subsets.

Markers of inflammation in patients with symptomatic and asymptomatic carotid artery stenosis: a case-control study.

Objectives: There is evidence that inflammation plays a role in the pathogenesis of atherosclerosis. We compared levels of inflammatory markers between patients undergoing carotid endarterectomy (CEA) and controls, and between patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis.

Materials And Methods: A total of 180 patients with ICA stenosis were compared with 180 age-matched and sex-matched controls.

Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation.

We have used a multiplex bead array assay to detect simultaneously 25 different circulating cytokines in 35 control subjects (young versus old) and 29 patients (young versus old) with acute infection. Intracellular PBMC levels of heat shock proteins (Hsp) were determined using flow cytometry. Levels of MIG and IL-6 were higher in the elderly normal subjects and patients, respectively, compared to their young counterparts.

Diagnostic accuracy of the FIDIS multiplex fluorescent microsphere immunodetection system for anti-extractable nuclear antigen (ENA) antibodies in connective tissue diseases.

Background: Anti-extractable nuclear antigen antibodies (ENA) are markers of connective tissue diseases (CTDs).

Methods: We compared FIDIS reagents in the multiplex fluorescent microsphere immunodetection system to INNO-LIA and immunodiffusion for 174 antinuclear antibody-positive patients, 102 with well-defined CTDs and 72 disease controls.

Results: No significant differences were found in sensitivity or specificity between FIDIS and immunodiffusion, or between FIDIS and INNO-LIA for all anti-ENA in all CTD patients; nor were any differences found for individual anti-ENAs within distinct CTDs.

Basal and infection-induced levels of heat shock proteins in human aging.

Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation.

Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands.

NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission.

Soluble HLA-G in rheumatoid arthritis.

We investigated potential correlations between soluble HLA-G (sHLA-G) and soluble HLA class I (sHLA-I) levels, respectively, and parameters of disease activity or genetic factors determined by HLA-DRB1 and HLA-DQB1 in patients with rheumatoid arthritis (RA). SHLA-G plasma concentrations from 106 RA patients (mean age 59.8 years, 80 women) were assessed by a sensitive enzyme-linked immunosorbent assay format.

Comparison of two ELISAs for the determination of Hsp70 in serum.

We have compared a previously developed in-house Sandwich-ELISA with a commercial kit for the determination of heat shock protein (Hsp) 70 in serum. Samples from 64 participants were tested and there was a significant correlation between results obtained using the two assays (r = 0.807, p < 0.

Heat shock protein 32 in human peripheral blood mononuclear cells: effect of aging and inflammation.

The purpose of the present study was to assess the influence of age and acute infection on the production of Hsp32 in human peripheral blood cells, using flow cytometry. Thirty-five controls and 31 patients with acute infection participated. We found that the age and inflammatory status correlated positively with Hsp32 levels in both heat shocked (HS) and non-HS monocytes and lymphocytes.

Biochemical changes in response to intensive resistance exercise training in the elderly.

Background: It is assumed that low-grade inflammation, characterized by increased circulating IL-6 and TNF-alpha, is related to the development of sarcopenia. Physical exercise, especially high intensity resistance training, has been shown to be effective in restoring the strength deficit in the elderly. Intensive exercise is accompanied by significant release of IL-6 and TNF-alpha into the blood circulation, but does not result in muscle wasting.

The influence of celecoxib on muscle fatigue resistance and mobility in elderly patients with inflammation.

Background: Acute inflammation has a negative effect on the muscular system in elderly patients, compromising the outcome of the underlying disease.

Objective: The aim of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibition on muscle performance and mobility in hospitalized elderly patients with acute inflammation of infectious origin.

Methods: In this single-blind, controlled trial, consecutively hospitalized elderly patients (age > or = 70 years) with inflammation (C-reactive protein [CRP] levels > or =10 mg/L) due to acute infection were randomly assigned to receive 2 weeks of treatment with the COX-2-selective inhibitor celecoxib, acetaminophen, or no supplementary medication (control).

Circulating acute phase mediators and skeletal muscle performance in hospitalized geriatric patients.

Background: There is growing evidence for the significant involvement of inflammatory processes in the development of muscle wasting in old age. Therefore, any disease accompanied by inflammation can be threatening to the muscle function in geriatric patients.

Methods: Sixty-three hospitalized geriatric patients (42 female, 21 male; mean age 84.

Persistent synovitis in children with Lyme arthritis: two unusual cases. An immunogenetic approach.

Unlabelled: We report on two patients with a persistent Lyme arthritis. In addition both had a peculiar disease history. The first patient had oligoarticular juvenile idiopathic arthritis in remission.

Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack?

Human leukocyte antigen (HLA) class I antigen defects may have a negative impact on the growing application of T-cell-based immunotherapeutic strategies for treatment of leukemia. Therefore in the present study, taking advantage of a large panel of HLA class I allele-specific human monoclonal antibodies, we have compared HLA class I antigen expression on leukemic cells with that on autologous and allogeneic normal cells. Down-regulation of HLA-A and/or -B allospecificities was present in the majority of the patients studied.

The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers.

The induction of heat shock proteins (Hsp) is the response to a plethora of stress signals including hyperthermia, physical stress, and various disease states. Although changes in Hsp expression are associated with certain diseases, the question as to whether this is an adaptation to a particular pathophysiologic state or a reflection of the suboptimal cellular environment associated with the disease remains open. In this study we have investigated the effects of inflammatory mediators on the induction of Hsp 70 in human peripheral mononuclear blood cells using flow cytometry.