PubMed Health⌕ Search

Biomedical subjects

H Grosse-Wilde

Publications and source records attributed to H Grosse-Wilde.

At least 19 recordsLinked to original sources
PubMed2006

Expression and function of Toll-like receptor 9 in severely injured patients prone to sepsis.

The purpose of this prospective study was to enumerate Toll-like receptor 9 (TLR9)(+) cells and measure their function using synthetic oligonucleotides enriched in CG dinucleotide motifs (CpG)-induced proliferation within 48 h after trauma in severely injured patients prone to sepsis. Sixteen consecutive trauma patients with an injury severity score (ISS) > 21 and 16 blood donors (controls) were included in this study. Using two-colour flow cytometry, TLR9 expression was detectable intracellularly and also on the surface of B lymphocytes. The surface expression of TLR9 of B lymphocytes from whole blood and peripheral blood mononuclear cells (PBMC) stimulated with CpG was significantly increased in B cells of severely injured patients prone to sepsis compared to controls. No significant differences could be observed between CpG-induced proliferation of PBMC of severely injured patients prone to sepsis and controls. As a measure of immunosuppression, human leucocyte antigen (HLA)-DR expression of monocytes of the trauma patients was significantly diminished compared with controls in PBMC and in whole blood. Immunosuppression in the early phase after trauma seems not to be associated with a disturbed sensing of bacterial DNA.

Adult↗
PubMed2006

Sequence-based typing reveals a novel DLA-88 allele, DLA-88*04501, in a beagle family.

The dog is an important animal model for solid organ as well as stem cell allo transplantation. Methods such as cellular and serological typing and more recently sequence-based typing (SBT) have been used to discriminate tissue antigen disparity of donor and recipient. We applied SBT for the canine class I (DLA-88) and class II (DLA-DRB1) genes in beagle families prior stem cell transplantation. A novel DLA-88 (DLA-88*04501) allele in combination with a DLA-DRB1*01901 allele was found. Sequence comparison of exons 2 and 3 of the novel allele revealed most sequence identity to the DLA-88*01301 allele (96.15% identity at the nucleotide and 90.65% identity at the protein level).

Alleles↗
PubMed2005

Behcet's disease is associated with increased concentrations of antibodies against phosphatidylserine and ribosomal phosphoproteins.

BACKGROUND: Although Behcet's disease (BD) is classified among the vasculitides laboratory diagnostic does not include regularly autoantibodies associated with vascular manifestations of systemic autoimmune diseases. PATIENTS AND METHODS: Twelve consecutive BD patients were studied for autoantibodies associated with vascular manifestations of systemic autoimmune diseases, HLA frequencies, and possible neurological involvement using neurophysiological methods and MRI. RESULTS: HLA-C*15 and C*16 frequencies were significantly (p < 0.05) higher in the patients compared with a reference population. Immunoglobulin G concentrations of antiphosphatidylserine and antiribosomal phosphoprotein antibodies were significantly elevated in BD patients when compared with healthy controls. CONCLUSIONS: The increased frequencies of HLA-C alleles in BD patients may stress the role of NK cells in the pathogenesis of this disease. Antiphosphatidylserine autoantibodies may in view of their role in apoptosis be involved in the development of vasculitis in BD. Because concentrations of antiphosphatidylserine and antiribosomal phosphoprotein antibodies were increased in BD diagnostic tools of this disease should be extended with humoral parameters associated with vascular manifestations of systemic autoimmune diseases.

Adult↗
PubMed2004

Impact of HLA-A,B,C allele mismatches on outcome after unrelated blood stem cell transplantation in whites.

At our institution the selection of unrelated donors for hematopoietic stem cell transplantation (HSCT) relies on low resolution human leukocyte antigen (HLA)-A,B and high resolution HLA-DRB1,DQB1 DNA-based typing. To answer the question of whether routine high resolution HLA-A,B,C typing might improve HSCT outcome, 171 white "HLA-identical" donor/recipient pairs, as stated by our pretransplant tissue typing routine, were retyped for HLA-A,B,C using sequence based typing (SBT). The numbers of HLA-A,B,C allele mismatches detected by SBT were correlated to established clinical endpoints of HSCT outcome. We found 33.9% of the study transplants to be fully HLA-A,B,C matched, whereas 66.1 % exhibited one through four donor/recipient HLA-A,B,C allele mismatches. However, statistical analysis could not demonstrate an impact of the number of HLA-A,B,C allele mismatches on overall survival and other analyzed endpoints. Thus, our series of white donor/recipient pairs does not suggest the routine use of HLA-A,B,C SBT to improve HSCT outcome substantially.

Alleles↗
PubMed2004

Soluble HLA class I and HLA-DR plasma levels in patients with anterior uveitis.

Anterior uveitis (AU) is an autoimmune disease frequently associated with HLA-B27 antigen. Because of the immune regulatory properties of soluble human leukocyte antigen (sHLA) molecules, we quantified sHLA class I (sHLA-I) and sHLA-DR plasma levels in HLA-typed AU patients (n = 60). Randomly selected healthy individuals (n = 128) and HLA-B27 antigen-positive individuals (n = 24) with HLA phenotype frequencies similar to the HLA-B27 antigen-positive AU patients served as control panels. As expected, HLA-B27 phenotype was significantly increased in AU patients (n = 60), compared to healthy controls. Mean sHLA-I levels in AU patients were slightly higher than in randomly selected healthy controls. Regarding AU subgroups, elevated sHLA-I levels were only found in HLA-B27 antigen-negative patients. Compared to controls, sHLA-DR levels were significantly increased in AU patients and the subgroups of HLA-B27 antigen-negative and -positive patients but not Fuchs' heterochromic cyclitis (FHC). AU patients negative for HLA-B27 antigen with a chronic course had higher sHLA-DR levels than those with an acute course. The presence of associated systemic diseases in AU patients was related to elevated sHLA-DR levels. Secretion of sHLA-DR in blood differs among the various forms of AU. Systemic immune activation was present in AU but not in FHC.

HLA-DR Antigens↗
PubMed2003

Effect of atorvastatin and clopidogrel on cellular immune function.

Lipid lowering therapy by statins and antiaggregation have become the basis of any anti-atherosclerotic prophylaxis either as primary or secondary prophylaxis. As several recent papers indicated immunosuppressive properties of statins we investigated changes in lymphocyte subpopulations, apoptosis markers, and cellular immune response towards mitogens after a short-term therapy with atorvastatin and clopidogrel. Nine healthy volunteers (four male, five female, age ranging from 26 to 43 years) were treated with 20 mg atorvastatin for 4 weeks and for 2 additional weeks with 20 mg atorvastatin and 75 mg clopidogrel after oral consent was given. Lymphocyte subpopulations were counted by flow cytometry. To assess cellular in vitro immune function, lymphocyte transformation tests with four mitogens (PHA, ConA, PWM, and OKT3) were performed. Absolute leucocyte counts remained unchanged as well as the granulocyte, monocyte, lymphocyte, and lymphocyte subpopulation counts. There were no detectable changes in markers of cell activation (HLA-DR, CD25, CD69, and CD86) or apoptosis (CD95, annexin). Cellular in vitro responses towards four mitogens did not show significant changes after atorvastatin nor after atorvastatin plus clopidogrel treatment.In conclusion, our data show that atorvastatin is not an immunosuppressive drug under therapeutical conditions.

Adult↗
PubMed2003

Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G.

During pregnancy the fetus represents a semi-allograft. Both membrane-bound and soluble forms of the nonclassic human leukocyte antigen (HLA)-G protect the fetus from maternal immune attack. To assess the relevance of soluble HLA-G (sHLA-G) levels in the maternal circulation for the occurrence of characteristic pregnancy disorders, we analyzed sHLA-G plasma levels of women with normal and pathological pregnancies. Compared to normal pregnancy, significantly increased sHLA-G levels were detected in women delivered preterm because of intrauterine activation (uncontrollable labor, rupture of fetal membranes, cervical insufficiency) and women with Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome. Contrary to these disorders, the sHLA-G levels in women with placental abruption were more than three times lower than in normal pregnancy (p < .0001). Nonparametric discriminant analysis showed that women with sHLA-G levels below 9.95 ng/mL had a relative risk of 7.12 for the development of placental abruption during further course of pregnancy. These results suggest that the occurrence of pregnancy-associated diseases is strongly influenced by maternal sHLA-G plasma levels.

Abruptio Placentae↗
PubMed2003

Molecular genetic and biochemical analysis of woodchuck (Marmota monax) MHC class I polymorphism.

The woodchuck (Marmota monax) is an animal model that is used in the study of human hepatitis B virus ( HBV ) infection. A knowledge of woodchuck MHC class I (Mamo-I) genes and gene products is therefore essential for understanding the antigen-specific T-cell responses in this animal model. A number of Mamo-I genes have been identified by molecular cloning and sequencing. However, the allelic nature of these genes has not been proven by classical genetics like the segregation analysis in families. In this study, we analyzed the allelic diversity of Mamo-I in two three-generation woodchuck families including 15 members by sequencing of Mamo-I genes and immunoblotting of Mamo-I proteins after one-dimensional isoelectric focusing (1D-IEF). In addition to four published Mamo-I alleles, six new alleles that belonged to the same locus as the known Mamo-I alleles (Mamo-A) were found within the two woodchuck families. A typical Mendelian segregation of Mamo-I gene and antigens was observed in the families studied. For simple and rapid detection of allelic variability of Mamo-I gene, a typing method based on the detection of PCR products amplified by sequence specific primers (SSP) has been developed and tested in 41 unrelated animals. The most prevalent allele was Mamo-A*01 with a frequency of 21.9% followed by Mamo-A*07 (12.2%). Our study established Mamo-A as a classical MHC class I locus by the polymorphic and allelic nature of Mamo-I gene in the woodchuck.

Amino Acid Sequence↗
PubMed2003

Specificity and functional characteristics of anti-HLA-A mAbs LGIII-147.4.1 and LGIII-220.6.2.

Only three anti-HLA-A monoclonal antibodies (mAbs) have been described in the literature. Two of them recognize determinants shared by only a few HLA-A allospecificities. The third one, mAb 3G11, recognizes a determinant shared by most HLA-A allospecificities. Being an IgM, the latter mAb is not likely to be a useful probe in immunohistochemical reactions and in functional assays. Therefore, in the present study we have characterized the specificity of the mAbs LGIII-147.4.1 and LGIII-220.6.2. The two mAbs that do not share idiotypic determinants recognize distinct but spatially close antigenic determinants expressed on most of the gene products of the HLA-A locus. Specifically, the determinant recognized by mAb LGIII-220.6.2 is expressed on HLA-A1, -A2, -A3, -A26, -A28, -A29, -A30, -A33, -A36, -A74 and -A80 allospecificities. The determinant recognized by mAb LGIII-147.4.1, which appears to be located on the amino-acid residues 79-83 of the heavy chain, is expressed on all HLA-A allospecificities but HLA-A23, -A24, -A25 and -A32. Because of its broad reactivity, the mAb LGIII-147.4.1 was characterized in a number of assays. It was found to be a useful probe to measure the HLA-A antigen level in serum, to assess the HLA-A restriction of cytotoxic T lymphocytes (CTL) and to monitor HLA-A antigen expression in normal and malignant lesions.

Animals↗
PubMed2003

ELISpot: a new tool for the detection of nickel sensitization.

BACKGROUND: The standard assay for the clinical detection of contact allergy against nickel is the patch test. For research purposes, the in vitro lymphocyte transformation test (LTT) is mostly applied. However, the in vivo application of allergens includes the potential of sensitization, whereas the LTT demands 6 days of cell culture and radioactive labelling procedures. OBJECTIVE: The purpose of this study was to validate an enzyme-linked immunospot (ELISpot) assay to specifically detect cellular response against nickel sulphate in correlation with patch test, anamnestic data, and LTT results. METHODS: In probands with positive (n=60) and negative patch test results (n=19), cytokine ELISpot and LTT were performed in parallel using various concentrations of nickel sulphate, various numbers of responding peripheral blood mononuclear cells (PBMC), and various durations of cell cultures. RESULTS: Concentrations of 50 and 75 microM nickel sulphate were found to be optimal to stimulate in the ELISpot 4x10(5) and in the LTT 2x10(5) PBMC, respectively. An increase in ELISpot sensitivity was reached by pre-incubation with nickel sulphate for 24 h prior to transfer to ELISpot plates. In nickel-sensitive probands, an average precursor cell frequency of 19x10(5), 1.7x10(5), and 0.7x10(5) could be defined for IFN-gamma, IL-2, and IL-4 producing PBMC, respectively. In non-sensitive probands IFN-gamma producing cells were detectable, but with significantly lower frequency (2x10(5); P=0.004). The prior performance of patch tests had no significant effect on cytokine production or lymphocyte proliferation. Overall, the parameters patch test, anamnestic nickel allergy, ELISpot, and LTT results were positively correlated (P<0.05). CONCLUSIONS: Based on these experiments, the quantitative in vitro detection of cell-mediated reactions towards nickel as well as other heavy metal ions should be possible utilizing the above-described ELISpot assay.

Adolescent↗
PubMed2003

Soluble HLA-DR and soluble CD95 ligand levels in pregnant women with antiphospholipid syndromes.

Antiphospholipid syndrome (APS) is a severe complication in pregnancy that can lead to fetal death in the second or third trimester. As soluble HLA-DR (sHLA-DR) molecules are reported to be implicated in the etiology of pregnancy disorders and of autoimmune diseases, we studied sHLA-DR plasma levels in pregnant women with APS (n = 14) and in women with normal pregnancy (n = 15), in women with high-risk pregnancies such as preeclampsia (PE; n = 20) and intrauterine growth retardation (IUGR; n = 10) and in fertile non-pregnant women (n = 29). The sHLA-DR levels of pregnant women were assessed during the third trimester, at labor, in the first week, and in the third month of puerperium. The results obtained were compared with soluble CD95 ligand (sCD95L), an important signal molecule in the apoptosis pathway. The sHLA-DR levels in pregnant women with APS were approximately three times higher (mean 1.48 +/- 0.15 microg/ml) during the whole observation period than in fertile non-pregnant women (0.54 +/-.06 microg/ml) and nearly double in women with high risk (PE, 0.91 +/- 14 microg/ml; IUGR, 0.94 +/-.21 microg/ml) and in normal pregnancies (0.74 +/- 0.13 microg/ml). Furthermore, sHLA-DR levels of pregnant women with APS were positively correlated with the serum concentration of anti-anticardiolipin immunoglobulin G antibodies. For sCD95L plasma levels, no substantial variations were found among the different groups above. In pregnant women with APS, however, sHLA-DR levels were positively correlated with sCD95L levels. Further studies should clarify the functional involvement of sHLA-DR molecules in the induction of CD95/CD95L-mediated apoptosis pathway that may play a crucial role in the pathology of pregnancies complicated by APS.

Adult↗
PubMed2002

Allogeneic CD34+ -selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases.

Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.

Acute Disease↗
PubMed2001

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗
PubMed2001

Soluble human leukocyte antigen--G serum level is elevated in melanoma patients and is further increased by interferon-alpha immunotherapy.

BACKGROUND: The nonclassic human major histocompatibility complex class I antigens human leukocyte antigen (HLA)--G are proposed to protect tumor cells from natural killer cell lysis. In the current study, the authors measured soluble HLA-G molecules (sHLA-G) in serum from patients with malignant melanoma. METHODS: Soluble HLA-G was determined in serum samples of 190 melanoma patients with various stages of disease, with or without current therapy including interferon (IFN)-alpha and different cytostatics in comparison to 126 healthy controls by using a two-step enzyme-linked immunoadsorbent assay. RESULTS: Serum sHLA-G was significantly (P < 0.0005) elevated in melanoma patients (mean +/- standard error of the mean [SEM] = 41.95 +/- 2.15 ng/mL) compared with healthy controls (mean +/- SEM = 22.92 +/- 1.51 ng/mL). Univariate analysis revealed a correlation of sHLA-G serum level with advanced stages of disease (P < 0.001) and tumor load (P < 0.05). Patients undergoing immunotherapy with IFN-alpha (n = 31) showed an increased serum sHLA-G (mean +/- SEM = 62.05 +/- 7.58 ng/mL; P < 0.0005), whereas other treatment regimens (n = 24) did not influence sHLA-G serum concentrations. Multivariate analysis revealed treatment with IFN-alpha as the only impact factor for elevated serum sHLA-G, lacking any correlation with stage of disease or tumor burden. Furthermore, IFN-alpha was found to upregulate HLA-G cell surface expression on circulating monocytes. sHLA-G serum level was not associated with recurrence free or overall survival. CONCLUSIONS: This study shows increased sHLA-G serum concentrations in melanoma patients and additional enhancement upon treatment with IFN-alpha. The level of serum sHLA-G, however, had no negative impact on patients' prognosis.

Antibodies, Monoclonal↗
PubMed2001

The G protein beta3 subunit 825T allele is a genetic marker for enhanced T cell response.

The G protein beta3 subunit (GNB3) 825T allele is predictive of enhanced Gi protein activation. Studying the influence of C825T allele status on cellular in vitro immune responses towards recall antigens and interleukin-2 stimulation we observed a 2-4-fold, significantly increased proliferation in homozygous 825T (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4(+) T cell counts of individuals with TT+TC genotypes were significantly enhanced compared to the CC genotype. In summary, it appears that C825T allele status is highly predictive of immunocompetence and could be a candidate gene in disorders associated with inadequate immune response.

Alleles↗