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Comparable Percentage (comparable + percentage)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Reduced CD4+,CD25, T cell sensitivity to the suppressive function of CD4+,CD25high,CD127,/low regulatory T cells in patients with active systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 7 2008
Ram Kumar Chowdary Venigalla
Objective CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo,preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127,/low natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. Methods CD4+,CD25high,CD127,/low nTreg cells and CD4+,CD25, responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. Results Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127,/low was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean ± SEM 2,223 ± 351 counts per minute versus 9,104 ± 1,720 cpm, respectively), while in normal donors, these values were 802 ± 177 cpm and 2,028 ± 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25, Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127,/low nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. Conclusion This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE. [source]

Clinical impact of altered immunoglobulin levels in Henoch,Schönlein purpura

PEDIATRICS INTERNATIONAL, Issue 3 2009
Andrew Fretzayas
Abstract Background:, The aim of the present study was the identification of immunological features, present at the time of diagnosis, that would predict the severity of Henoch,Schönlein purpura and its outcome. Methods:, A cohort study was carried out in a tertiary pediatric hospital of 69 children with Henoch,Schönlein purpura, in whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly determined. Results:, During the acute phase of the disease in 54/69 patients (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain complications involving the kidneys and the gastrointestinal tract were noted as opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69 children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed renal involvement while only 1/19 children (5.3%) with normal IgA concentration had renal involvement. Considering separately the group of 9/69 children (13%) with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective of IgA and IgG concentration, we found a comparable percentage of children who had both renal and intestinal involvement without, however, developing severe complications, which were exclusively seen in patients with increased IgA (5/7 children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children (37.7%) and in 73% of cases it was associated with increased serum IgA values. Conclusion:, Renal involvement was seen in 32% of children with increased IgA values. Most importantly, elevated IgA concentration along with reduced IgM levels was associated with higher prevalence of severe complications. [source]

Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal,induced inflammation in mice

ARTHRITIS & RHEUMATISM, Issue 7 2010
Hal M. Hoffman
Objective The mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activate the cryopyrin inflammasome is unknown. The aim of this study was to use a mouse molecular genetics,based approach to test whether the leucine-rich repeat (LRR) domain of cryopyrin is required for MSU crystal,induced inflammation. Methods Cryopyrin-knockout lacZ (Cryo,Z/,Z) mice and mice with the cryopyrin LRR domain deleted and fused to the lacZ reporter (Cryo,LRR Z/,LRR Z) were generated using bacterial artificial chromosome,based targeting vectors, which allow for large genomic deletions. Bone marrow,derived macrophages from Cryo,LRR Z/,LRR Z mice, Cryo,Z/,Z mice, and congenic wild-type (WT) mice were challenged with endotoxin-free MSU crystals under serum-free conditions. Phagocytosis and cytokine expression were assessed by flow cytometry and enzyme-linked immunosorbent assay. MSU crystals also were injected into mouse synovial-like subcutaneous air pouches. The in vivo inflammatory responses were examined. Results Release of interleukin-1, (IL-1,), but not CXCL1 and tumor necrosis factor ,, was impaired in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mouse bone marrow,derived macrophages compared with WT mouse bone marrow,derived macrophages in response to not only MSU crystals but also other known stimuli that activate the cryopyrin inflammasome. In addition, a comparable percentage of MSU crystals taken up by each type of bone marrow,derived macrophage was observed. Moreover, total leukocyte infiltration in the air pouch and IL-1, production were attenuated in Cryo,Z/,Z and Cryo,LRR Z/,LRR Z mice at 6 hours postinjection of MSU crystals compared with WT mice. Conclusion MSU crystal,induced inflammatory responses were comparably attenuated both in vitro and in vivo in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mice. Hence, the LRR domain of cryopyrin plays a role in mediating MSU crystal,induced inflammation in this model. [source]

Optimizing open live-donor nephrectomy , long-term donor outcome

CLINICAL TRANSPLANTATION, Issue 3 2004
M Schostak
Abstract:, Introduction:, The technique of laparoscopic or retroperitoneoscopic donor nephrectomy has been increasingly propagated in recent years. The central advantage is supposed to be a reduction of perioperative discomfort. However, there have not been many reports describing the subjective feeling associated with an open donor nephrectomy, particularly with respect to the pain level in the perioperative and long-term course. This retrospective study examines the perioperative pain and morbidity and long-term outcome of living kidney donors from 35 yr of experience at the University Hospital Benjamin Franklin of the Free University of Berlin. Methods:, A total of 102 living kidney donors were asked to fill out a questionnaire. Five epidemiological questions were posed and the rest dealt mainly with lasting subjective and objective surgical impairments. There were also questions relating to the perioperative pain level (VAS/NAS-Score). In addition, basic information was obtained regarding the donor's current health status (physical examination, serum creatinine; sometimes also ultrasound, protein IU, blood pressure), and/or examinations were performed. Results:, The mean age at the time of donation was 45.5 and 55% were women. Donor nephrectomies were left-sided in 78 cases and right-sided in 24. There was a total complication rate of 53%, but serious complications only occurred in two cases (1.9%). A total of 53 donors could be reached. Although 41.5% felt they had a lasting impairment, somatic sequelae like respiratory, abdominal or scar problems were rare, affecting a maximum of only four patients in each case. Fifteen patients reported neurological problems such as sensory disturbances. The mean serum creatinine was 89.9 ,mol/L in female and 114.2 ,mol/L in male donors. Microalbuminuria was found in 22.6% of the donors, hypertension in 35.8%. Persistent pain was reported by 20.7%, its occurrence being permanent in two of the donors and very frequent in one. All the others rarely have pain. The median perioperative VAS/NAS score was 8 on the first day after surgery, 5 after 1 wk and 1 after 1 month. The analgesia was rated as good or very good by 71%. Everyday life was managed as well as before surgery after 2,4 wk by the highest percentage (42%) of patients, but working capacity was only regained after 1,3 months by a comparable percentage (44%). Forty-six percent had a very good and 33% a good feeling after the kidney donation. The relationship to the recipient had intensified in most cases. Ninety-one percent would again decide in favor of a donation. Conclusion:, Donor nephrectomy in an open technique is a safe and reliable procedure with low morbidity. After a median post-operative period of 7 yr, however, 42% of the donors still report general impairment due to the intervention, although concrete somatic problems were only detected in a few cases. Nearly all these patients underwent surgery in a full flank position. Wound-healing impairments were also significantly more frequent with this surgical technique. This positioning should thus be avoided. The post-operative pain level was relatively high, but a marked improvement was achieved in the course of the observation period by optimizing analgesic management. [source]