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2.
J Viral Hepat ; 16(10): 743-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19486277

ABSTRACT

Prevalence data concerning viral hepatitis and human immunodeficiency virus (HIV) in the general population are usually scarce. We aimed for a large cohort representative of the general population that required little funding. Autologous blood donors are relatively representative of the general population, and are tested for viral hepatitis and HIV in many countries. However, frequently these data are not captured for epidemiologic purposes. We analysed data from well over 35,000 autologous blood donors as recorded in 21 different transfusion centres for anti-hepatitis C virus (HCV), HBsAg and anti-HIV, as well as TPHA if available. We found a lower prevalence of hepatitis B virus and HCV in East vs West Germany, 0.2%vs 0.32% and 0.16%vs 0.32% respectively, which confirms earlier data in smaller cohorts, thus supporting the value of our approach. HIV was too rare to disclose significant differences, 0.01%vs 0.02%. TPHA was higher in East (0.34%) vs West Germany (0.29%) without significant differences. HCV was more frequent in women vs men. Transfusion institutes managing autologous blood donations should be used as a resource for epidemiological data relating to viral hepatitis and HIV, if such testing is performed routinely. This approach generates data relating to the general population with special emphasis on undiagnosed cases.


Subject(s)
Health Resources , Hepatitis, Viral, Human/epidemiology , Blood Transfusion, Autologous , Female , Germany, East/epidemiology , Germany, West/epidemiology , HIV , HIV Antibodies/blood , HIV Infections/epidemiology , HIV Infections/virology , Hepacivirus , Hepatitis B Surface Antigens/blood , Hepatitis B virus , Hepatitis, Viral, Human/virology , Humans , Male , Mass Screening , Prevalence
3.
Bone Marrow Transplant ; 43(11): 875-81, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19151793

ABSTRACT

Relapse after allo-SCT in patients with acute leukaemia remains a major problem. A beneficial impact of alloreactive natural killer (NK) cells has been reported for myeloid malignancies, but has been questionable for B-lineage ALL. We analysed lysis of primary paediatric precursor-B-ALL blasts by 285 NK cell clones to investigate whether HLA class I expression on the blasts and phenotypic killer cell Ig-like receptor (KIR) expression on NK cells affect the lytic activity against ALL blasts. Precursor-B-ALL blasts with low HLA-I expression were lysed by a majority (79%) of NK cell clones, whereas those with high HLA-I expression showed low susceptibility to NK clones independent of their KIR expression patterns. NK cell activity against susceptible blasts was regulated by differential surface expression of the three major KIRs (CD158a, CD158b, CD158e). NK clones with none of these three KIRs or a single KIR that recognized no ligand, were not inhibited by the targets and exerted higher lysis (P = <0.0005) in comparison to NK clones expressing KIRs with a ligand on the ALL blasts. In conclusion, the quantity of HLA-I expression on precursor-B-ALL blast regulates overall NK cell susceptibility; in case of reduced HLA expression, differential surface expression of KIRs affects NK cell alloreactivity against those blasts.


Subject(s)
Histocompatibility Antigens Class I/genetics , Killer Cells, Natural/immunology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Receptors, KIR/genetics , Histocompatibility Antigens Class I/immunology , Humans , Phenotype , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Receptors, KIR/immunology
4.
Cell Mol Life Sci ; 62(1): 77-86, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15619009

ABSTRACT

Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/analysis , Humans , Immunodominant Epitopes/immunology , Immunotherapy, Adoptive/methods , Vaccines, Subunit/immunology , Viral Vaccines/immunology
7.
Cell Mol Life Sci ; 59(6): 1076-80, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12169019

ABSTRACT

Human cytomegalovirus (HCMV) persists after infection but is controlled by cellular immune responses, particularly by CD8+ T cells. If infected individuals are immunosuppressed, HCMV can be reactivated. Upon testing the blood of healthy donors with human lymphocyte antigen tetramers, we found one individual with about 50% of his CD8+ T cells being specific for the immunodominant pp65 epitope NLVPMVATV Over a period of 2 years the high level of HCMV-specific T cells was maintained, and no HCMV DNA could be detected. At one timepoint, however, HCMV-specific DNA was detected, while 65% of CD8+ T cells were specific for HCMV. When virus was detectable, a lower percentage of HCMV-specific CD8+ T cells showed interferon gamma (IFN-gamma) production after peptide stimulation in vitro. These data suggest that HCMV reactivation may also occur in immunocompetent persons, accompanied by the presence of HCMV-specific CD8+ T cells which are not producing IFNy, and therefore potentially anergic or in vivo exhausted.


Subject(s)
Blood Donors , CD8-Positive T-Lymphocytes/virology , Cytomegalovirus/isolation & purification , Humans , Interferon-gamma/biosynthesis , Male , Middle Aged , Phenotype , T-Lymphocytes, Cytotoxic/virology
8.
Tissue Antigens ; 58(3): 166-70, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11703824

ABSTRACT

The distribution of the different HLA-B*51 suballeles among patients with Behçet's disease (BD) of German (n=33) and Turkish (n=92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n=325, Turkish: n=93) was studied. HLA-B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P<0.001; Turkish: 75% vs. 25%, OR 9.13, P<0.001). Molecular subtyping of B*51x revealed HLA-B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA-B*5108 in the diseased individuals. HLA-B*5105 was the only further HLA-B*51x subtype detected in one Turkish patient heterozygous also for HLA-B*5101. HLA-B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA-B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino-acid residues at positions 63 and 67 as well as at positions 77-83 for specific peptide binding and natural killer (NK)-cell interactions. This applies to HLA-B*5101 and B*5108, but not to HLA-B*5107 different at position 67, which could be negatively associated with BD.


Subject(s)
Alleles , Behcet Syndrome/genetics , Genetic Predisposition to Disease , HLA-B Antigens/genetics , Gene Frequency , Genes, MHC Class I , Genotype , Germany , HLA-B51 Antigen , Heterozygote , Histocompatibility Testing , Homozygote , Humans , Turkey
9.
Proc Natl Acad Sci U S A ; 98(16): 9249-54, 2001 Jul 31.
Article in English | MEDLINE | ID: mdl-11459940

ABSTRACT

Mice prefer to mate with individuals expressing different MHC genes from their own. Volatile components presenting MHC-dependent odor types are present in urine and can be detected by mice, as shown by extensive behavioral studies. Similar odor types are suspected to influence human behavior as well. Although a recent report indicates that MHC expression influences the ratio of volatile compounds such as phenylacetic acid, so far no other means than studying the behavior of mice or rats has been available to assess odor types. Here, we report the ability of a gas sensor array (referred to as "electronic nose") to detect MHC-dependent odor types. The electronic nose consists of an array of chemophysical detectors, in our case quartz crystal microbalances and semiconducting metal-oxide sensors that change frequency or conductivity upon binding of very small numbers of individual molecules present in the gas phase of odorous fluids. The pattern of changes is characteristic for a particular smell. Our electronic nose distinguishes the urine odor types of MHC congenic mouse strains, MHC class I mutant mice, and HLA-A2 transgenic mice. In addition, MHC-dependent odor types can be detected in serum. The device also clearly differentiates between individual odor types of human sera from HLA homozygous individuals; however, HLA expression seems to have only a secondary influence. Thus, odor-type research can now be carried out with an objective and fast through-put system independent of behavioral studies.


Subject(s)
Kidney/chemistry , Major Histocompatibility Complex/genetics , Odorants , Animals , Blood , Gas Chromatography-Mass Spectrometry , Haplotypes , Mice , Mice, Mutant Strains , Mice, Transgenic , Species Specificity , Urine , Volatilization
10.
J Invest Dermatol ; 116(6): 891-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11407977

ABSTRACT

Vitiligo is a skin and hair disorder characterized by circumscribed depigmented lesions due to lack of melanocytes in the respective areas. It has been suggested that vitiligo is caused by an autoimmune-mediated destruction of melanocytes. Recently, the presence of a high frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in the peripheral blood of patients with vitiligo was reported. Our study examines the frequency of melanocyte-specific cytotoxic T lymphocytes in vitiligo patients and its relationship to disease activity. Thirty-two patients with moderate to active vitiligo and 17 control subjects were included. Melanocyte specific reactive CD8(+) T cells were identified by enzyme-linked immunospot assay after stimulation with five peptides from gp100, four peptides from MelanA/MART1, and two peptides from tyrosinase. In selected patients, intracellular interferon-gamma staining for the detection of specific reactive CD8(+) T cells was additionally performed. In seven of 10 patients (70%) with actively progressive disease CD8(+) T cells directed against melanocyte epitopes were detected, whereas only in four of 22 patients (18%) with moderate disease activity such specific reactivity was found. MelanA/MART1 peptides were immunodominant in nine patients reacting against EAAGIGILTV and three patients reacting against ILTVILGVL. Intracellular interferon-gamma staining confirmed the findings obtained by the enzyme-linked immunospot technique. The present study supports the hypothesis that vitiligo is a cytotoxic T lymphocyte-mediated autoimmune disease. The presence of melanocyte-specific reactive CD8(+) T cells seems to be closely related to disease activity.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , HLA-A2 Antigen/immunology , Melanocytes/immunology , Vitiligo/immunology , Adult , Aged , Antigens, Differentiation, T-Lymphocyte , Antigens, Neoplasm , Female , Humans , Interferon-gamma/biosynthesis , MART-1 Antigen , Male , Membrane Glycoproteins/analysis , Middle Aged , Neoplasm Proteins
11.
Int Immunol ; 13(7): 863-70, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11431416

ABSTRACT

Alloreactive T cells recognize framework or peptide-dependent determinants on foreign MHC molecules. Among the peptide-dependent alloreactive T cells a significant proportion is specific for one particular peptide presented by the allo-MHC molecule as antigen-specific T cells would do. Such alloreactive, peptide-specific T cells are referred to as 'allorestricted'. High-avidity HLA-A*02 allorestricted cytotoxic T lymphocyte (CTL) clones specific for peptide libraries can be generated from HLA-A*02(-) donors. We made use of this technique to study the role of closely related self-HLA molecules on shaping of the alloreactive T cell repertoire. Peripheral blood lymphocytes from HLA-A*0205 individuals were stimulated by HLA-A*0201 targets pulsed with an HLA-A*0201 peptide library. We did not observe a bias towards peptide-specific CTL in the HLA-A*0201-directed alloreactive repertoire of HLA-A*0205 donors as compared to HLA-A*02(-) donors. Comparison of the alloreactive T cell response between two donors having similar HLA haplotypes demonstrated that the allorestricted T cell repertoire is largely different between individuals.


Subject(s)
HLA-A2 Antigen/immunology , Peptides/immunology , T-Lymphocytes, Cytotoxic/immunology , Cell Line, Transformed , Cells, Cultured , HLA-A2 Antigen/genetics , Haplotypes , Humans , T-Lymphocytes, Cytotoxic/cytology
12.
Transplantation ; 69(8): 1742-4, 2000 Apr 27.
Article in English | MEDLINE | ID: mdl-10836395

ABSTRACT

BACKGROUND: Haploidentical bone marrow transplantation with preexisting anti-HLA antibodies is associated with a high risk of graft failure. METHODS: A 27-year-old female patient with chronic myeloid leukemia and evidence of several osseous chloromas had no suitable matched bone marrow donor, and fluorescence cytometric cross-match (FCXM) revealed antibodies against donor-specific HLA-molecules. Immunoadsorption onto staphylococcal protein A was applied to remove these antibodies, and peripheral stem cell transplantation was performed from her haploidentical sister after a negative FCXM was documented after immunoadsorption and conditioning treatment. RESULTS: FCXM for donor lymphocytes and stem cells remained negative throughout the posttransplant period, and engraftment of donor cells was documented on day +69. CONCLUSION: Immunoadsorption onto protein A should be considered in stem cell transplantation even from an haploidentical donor where anti-HLA antibodies and a positive FCXM are documented.


Subject(s)
Antigens, CD34/analysis , HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation , Immunization , Immunosorbent Techniques , Staphylococcal Protein A/therapeutic use , Stem Cells/immunology , Adult , Female , Flow Cytometry , Histocompatibility Testing , Humans
13.
Transfus Med ; 10(1): 77-80, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10760206

ABSTRACT

Sera of 500 female blood donors after pregnancy were tested for platelet-specific antibodies (HPA-1, 3, 5) using the MAIPA assay. Twenty-one sera (4.2%) were found to be positive: four anti-HPA-1a, one anti-HPA-5a and 16 anti-HPA-5b. Sera were positive up to 30 years after the last pregnancy. All women with antibodies were HLA-DR52 positive and 79% of the women with anti-HPA-5b were HLA-DR6 positive.


Subject(s)
Antigens, Human Platelet/immunology , Autoantibodies/immunology , Blood Donors , Blood Platelets/immunology , Female , Humans , Pregnancy/immunology
14.
Neurology ; 54(2): 485-7, 2000 Jan 25.
Article in English | MEDLINE | ID: mdl-10668719

ABSTRACT

Interferon (IFN)-beta, the most effective immunomodulatory treatment for MS, inhibits the proliferation of myelin-specific T cells. We report that IFN-beta moderately enhances the expression of the death receptor, CD95, at the surface of human antigen-specific T cells. However, T-cell apoptosis was not induced by IFNbeta-1a or IFNbeta-1b as assessed by caspase activity or DNA fragmentation. Immunomodulation mediated by IFN-beta does not directly involve apoptotic pathways in human T cells.


Subject(s)
Adjuvants, Immunologic/pharmacology , Apoptosis/drug effects , Apoptosis/immunology , Interferon-beta/pharmacology , Multiple Sclerosis/immunology , T-Lymphocytes/immunology , Caspase 3 , Caspases/immunology , Caspases/metabolism , Coumarins/metabolism , Coumarins/pharmacology , DNA Fragmentation , Epitopes , Fluorescent Dyes/metabolism , Fluorescent Dyes/pharmacology , Gene Expression/immunology , Humans , In Vitro Techniques , Myelin Basic Protein/immunology , Oligopeptides/metabolism , Oligopeptides/pharmacology , RNA, Messenger/analysis , T-Lymphocytes/enzymology , fas Receptor/genetics , fas Receptor/immunology
15.
Clin Infect Dis ; 29(6): 1604-5, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10585843
17.
Toxicol Lett ; 96-97: 177-80, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9820664

ABSTRACT

Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown etiology. The serum concentration of selenium (Se) was measured in 68 consecutive patients (nine male, mean age: 47 years; 59 female, mean age 49 years) with FM. The age- and sex-matched control group included 97 female healthy blood donors (mean age 46 years). The method is based on high-performance liquid chromatography (HPLC) involving detection of the fluorescent diaminonaphthalene (DAN) derivate of selenite. There was a statistical significant difference (P < 0.05) in serum Se between control (median 77 microg/l; range: 50-118 microg/l) and patients (median 71 microg/l; range: 39-154 microg/l) groups in the region of Tübingen, Germany.


Subject(s)
Fibromyalgia/blood , Selenium/blood , Adult , Age Factors , Chromatography, High Pressure Liquid , Female , Humans , Male , Middle Aged , Sex Factors
18.
Article in English | MEDLINE | ID: mdl-9356673

ABSTRACT

Experience with the MAIPA assay for the diagnosis of platelet-reactive antibodies has shown that high-titered antibodies falsify the test results. We here demonstrate 2 cases: i) A serum with high-titered HLA antibodies (100% panel reactivity in the LCT, titer between 4,000 and 12,000), and ii) Serum with a high-titered anti-HPA-1a (titer in the MAIPA assay 1,000). In both cases, it can be demonstrated that these antibodies led to unspecific reactions. In the 1st case, they interfered with the diagnosis of additional platelet-specific antibodies. Only the use of HLA-compatible platelets allowed a correct identification. On the other hand, in the high-titered anti-HPA-1a unspecific reactions were seen with the glycoproteins Ib/IX, Ia/IIa, and beta 2-microglobulin, leading to misinterpretations. These examples demonstrate that, in the test conditions as described, a correct diagnosis of high-titered sera might only be achieved by using compatible HLA or HPA cells.


Subject(s)
Blood Platelets/immunology , Immunoenzyme Techniques , Isoantibodies/blood , Platelet Membrane Glycoproteins/immunology , Aged , Aged, 80 and over , Antibodies, Monoclonal/immunology , Antibody Specificity/immunology , Blood Group Incompatibility/blood , Blood Group Incompatibility/diagnosis , Female , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/therapy , Middle Aged
19.
Transfus Med ; 6(2): 111-4, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8809957

ABSTRACT

The frequency and specificity of platelet-alloantibodies to human platelet antigens (HPA) -1, -3 and -5 was investigated in 59 multitransfused, HLA-immunized patients. Using the MAIPA test (monoclonal antibody specific immobilization of platelet antigens) platelet alloantibodies could be demonstrated in 10 (17%) patients. In one patient the antibody was present prior to any transfusions and probably induced by multiple previous pregnancies. This antibody was directed to HPA-5b. The remaining nine antibodies were found in patients (n = 36) with HLA-antibodies reacting with over 95% of unselected lymphocytes. In these patients the target antigens were HPA-1b in six, HPA-3a in one and both antigens in two patients. Our findings demonstrate platelet alloimmunization induced by transfusions to be restricted to patients with high HLA-immunization. 25% of these patients (9/36) show platelet-specific antibodies, primarily HPA-1b.


Subject(s)
Blood Platelets/immunology , HLA Antigens/immunology , Hematologic Neoplasms/immunology , Immunization , Isoantibodies/blood , Transfusion Reaction , Antibodies, Monoclonal , Antibody Specificity , Antigens, Human Platelet/immunology , Humans , Immunoassay/methods
20.
Vox Sang ; 71(4): 212-5, 1996.
Article in English | MEDLINE | ID: mdl-8958644

ABSTRACT

Reactivation of recipient antibody to HLA and red blood cell antigens is described in 8 patients after allogeneic bone marrow transplantation. These IgG antibodies can be detected between day 10 and day 40 after transplantation and, in 1 patient, can be shown to be antigen-independent. We hypothesize that, induced by graft recognition of recipient antigens, antigen-independent activation of sensitized recipient B cells takes place leading to transient antibody production.


Subject(s)
Antibodies/immunology , Bone Marrow Transplantation/immunology , Erythrocytes/immunology , HLA Antigens/immunology , Immunoglobulin G/immunology , Antibodies/blood , B-Lymphocytes/immunology , Female , Humans , Immunoglobulin G/blood , Lymphocyte Activation , Male , Transplantation, Homologous
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