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Biomedical subjects

V Rebmann

Publications and source records attributed to V Rebmann.

At least 19 recordsLinked to original sources
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

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

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

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↗
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

Immune response to perforated and partially demineralized bone allografts.

Immune responses have been shown to be involved in the pathogenesis of clinical complications of cortical bone allografts. In an attempt to reduce the immunogenicity of these allografts, we evaluated cortical bone allografts modified by laser perforation and partial demineralization transplanted orthotopically into sheep tibiae. The recipient animals were divided into three groups, of eight animals each, according to the type of cortical allograft that was transplanted: group 1, no treatment (control); group 2, demineralization only; and group 3, laser perforation and partial demineralization. All animals were tissue-typed by biochemical definition of MHC class I molecules, using unidimensional isoelectric focusing and Western blotting. Mismatches of donors and recipients were assessed by testing samples of each donor and recipient pair in parallel and by comparing their individual bands. Donor-specific alloantibodies were detected by a similar technique, using an enzyme-linked immunosorbent assay (ELISA) format. Negative controls were included in all tests. All grafts were poorly immunogenic, whether they were untreated, processed by partial demineralization, or processed by both laser perforation and partial demineralization. Only two recipient animals showed a transient, antibody-mediated donor-specific immune response. One of these animals had received a control allograft, whereas the other animal had received a laser-perforated and partially demineralized bone allograft. All of the grafts in this study, including control grafts, were stripped of soft tissues and their bone marrow was removed; cellular sources of alloantibody stimulation may have been eliminated by these processes. The results of this study suggest that immune responses to bone allografts may be reduced by removing the bone marrow and adjacent soft tissues. The processing of cortical bone allografts by laser perforation and partial demineralization appeared to have little effect on immune responses.

Animals↗
PubMed2001

Association of soluble HLA-G plasma levels with HLA-G alleles.

Soluble HLA-G (sHLA-G) molecules are found in the peripheral blood of healthy females and males, in cord blood and in amniotic fluids and discussed to be a mediator in maternal-fetal tolerance. In this study we investigated whether there are allele-specific differences in expression of sHLA-G molecules. For this, the sHLA-G plasma concentrations of 94 healthy unrelated individuals were measured by ELISA and correlated to their HLA-G genotypes, as determined by sequence analysis of exon 2 and 3 of the HLA-G gene. Mean sHLA-G levels in individuals with the most common HLA-G alleles G*01011 (27.0+/-2.1 SEM ng/ml, n=66), G*01012 (28.4+/-3.2 SEM ng/ml, n=34) were very similar. In contrast, individuals carrying the HLA-G*01013 (8.1+/-1.7 SEM ng/ml, n=17) or the "null" allele HLA-G*0105N (8.2+/-3.2 SEM ng/ml, n=7) presented significantly (P(c)=0.001 and P(c)<0.01, resp.) reduced sHLA-G levels. Furthermore, individuals with the HLA-G*01041 allele had significantly (P(c)=0.004) increased sHLA-G levels (42.5+/-4.6 SEM ng/ml, n=14). These results demonstrate that the generation of sHLA-G molecules is associated to certain HLA-G alleles and imply that sHLA-G levels are under genetic control. As low and high sHLA-G plasma levels did not segregate with HLA haplotypes including the HLA-G*01013 or *01041 allele, additional mechanisms may be involved in the regulation of the individual sHLA-G levels. Nevertheless, the existence of "low" and "high secretor" HLA-G alleles further suggests different levels of functionality in immune regulation.

Alleles↗
PubMed2001

Non-expression of HLA-B*5111N is caused by an insertion into the cytosine island at exon 4 creating a frameshift stop codon.

The identification of the "blank" allele HLA-B*5111N, which was detected in German and Czech individuals, is described. In the pedigree analysis this new allele segregates with the serological haplotype HLA-A2; B-; DR4 which is frequent in Czech population. The non-expression of B*5111N is caused by the insertion of an additional cytosine molecule at the cytosine island between the nucleotides 621-626 (codons 183-185, first three codons of exon 4) leading to a frame shift that creates a stop codon at codon 196. This insertion may be explained either by conversion with the pseudogene HLA-J or by slipped-strand mispairing. In order not to overlook the presence of alleles with altered expression in case of hematopoietic stem cell transplantation, both serological and DNA-based typing should be performed (Note).

Alleles↗
PubMed2000

Structural relatedness of distinct determinants recognized by monoclonal antibody TP25.99 on beta 2-microglobulin-associated and beta 2-microglobulin-free HLA class I heavy chains.

The association of HLA class I heavy chains with beta2-microglobulin (beta2m) changes their antigenic profile. As a result, Abs react with either beta2m-free or beta2m-associated HLA class I heavy chains. An exception to this rule is the mAb TP25.99, which reacts with both beta2m-associated and beta2m-free HLA class I heavy chains. The reactivity with beta2m-associated HLA class I heavy chains is mediated by a conformational determinant expressed on all HLA-A, -B, and -C Ags. This determinant has been mapped to amino acid residues 194-198 in the alpha3 domain. The reactivity with beta2m-free HLA class I heavy chains is mediated by a linear determinant expressed on all HLA-B Ags except the HLA-B73 allospecificity and on <50% of HLA-A allospecificities. The latter determinant has been mapped to amino acid residues 239-242, 245, and 246 in the alpha3 domain. The conformational and the linear determinants share several structural features, but have no homology in their amino acid sequence. mAb TP25.99 represents the first example of a mAb recognizing two distinct and spatially distant determinants on a protein. The structural homology of a linear and a conformational determinant on an antigenic entity provides a molecular mechanism for the sharing of specificity by B and TCRs.

Amino Acid Sequence↗
PubMed2000

Expression analysis of classic and non-classic HLA molecules before interferon alfa-2b treatment of melanoma.

Individual predictive clinical, immunological, or molecular features for definition of patients with lymph-node-positive melanoma who do not benefit from adjuvant postsurgery high-dose interferon alpha treatment are lacking. Expression analysis of classic and non-classic HLA molecules on melanoma cells metastatic to the locoregional lymph node may help select these patients before treatment.

Antineoplastic Agents↗
PubMed2000

Soluble HLA levels in early pregnancy after in vitro fertilization.

Intact pregnancy can be interpreted as a state of maternal immunotolerance toward an haploidentical fetus. Soluble HLA (sHLA) molecules increase during episodes of allograft rejection and are discussed as candidates to modulate immune responses. We questioned whether after in vitro fertilization (IVF) the subsequent intact pregnancy, early abortion, or tubal pregnancy influence the courses sHLA serum levels. Therefore, serum samples of 65 IVF patients were assayed by ELISA for sHLA-I, sHLA-G, and sHLA-DR concentrations preovulatorily and after a positive HCG test weekly until the 9th gestational week (GW). In 20 patients experiencing an early abortion the preovulatory sHLA-G mean level of 25.9 +/- 3.9 SEM ng/ml and the share of 4.2 +/- 0.8 SEM % on total sHLA-I were significantly (p < 0.05) reduced compared to women with intact pregnancy. The same differences (p < 0.0001) were seen during the monitoring of sHLA-G and sHLA-I levels in intact pregnancy versus early abortion until 9th GW. Twin pregnancy revealed a drastically increase of sHLA-G levels from the 8th GW compared to singleton pregnancies. Further, individual sHLA-DR levels increased during intact pregnancy but decreased in the group of early abortion. With regard to sensitivity and specificity for pregnancy outcome sHLA quantitation reached similar weight as routine HCG determinations at GW 5. Especially women with preovulatory low sHLA-G levels appear to be on risk for early abortion after IVF.

Abortion, Spontaneous↗
PubMed2000

Identification of the novel allele HLA-A*6813 in two members of a family of Syrian origin: implications for bone marrow transplantation.

The identification of the new allele HLA-A*6813, which was found in a woman of Syrian origin and her son, is described. In the sequence analysis the new allele differs from A*68011 by positions 259 (A>G) and 261 (C>G) in exon 2. As the structure is thus identical to the HLA-A consensus sequence it is likely that the new allele originated by gene conversion. At the protein level, the new allele has one amino acid difference from A*6801 (Asn63Glu), which results in a distinct banding pattern in one dimensional-isoelectric focusing. Amino acid residue 63 contributes to the formation of pocket A and B and is thus important for peptide binding. A*6813 was serologically detectable only by two of six polyclonal, but by three monoclonal antisera. The restricted serological A68 activity may be explained by altered peptide binding as presented peptides can affect the serological recognition of major histocompatibility complex (MHC) class I molecules. Moreover, our findings suggest that a possible mismatch with the other known A*68 variants may impair clinical outcome of bone marrow transplantation.

Alleles↗
PubMed2000

Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease-associated epitopes.

We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.

Adult↗
PubMed2000

Therapeutic immunoadsorption increases the level of circulating soluble HLA molecules.

BACKGROUND AND OBJECTIVES: Immunoadsorption (IA) is an established procedure to remove Igs and immune complexes from peripheral blood. Since Igs reportedly bind to human leucocyte antigen (HLA) molecules, we were interested to know whether removal of Ig will also influence the plasma concentration of soluble HLA (sHLA). PATIENTS AND METHODS: Nine patients suffering from severe autoimmune disease and undergoing 17 single courses of IA treatment were monitored for their sHLA class I (sHLA-I) and sHLA-DR plasma levels. Plasma was separated by a hollow-fiber-type separator. Plasma samples were taken before therapy, after 15 min of recirculation (without operating the adsorber), after 1 and 2 liters of plasma adsorption, and 24 and 48 h after the end of IA. RESULTS: Before treatment the mean levels of sHLA-I and sHLA-DR were 0.37 (+/-0.06 SEM) and 0. 32+/-0.05 microg/ml, respectively. After 2 liters of plasma filtration, an increase in sHLA-DR (0.80+/-0.10 microg/ml) was observed (p<0.001), whereas sHLA-I was only slightly affected (mean: 0.45+/-0.06 microg/ml). sHLA concentrations returned to initial levels after 24 h. CONCLUSION: The significant increase in sHLA-DR may contribute to the immunomodulatory effect of IA.

Antigen-Antibody Complex↗
PubMed1999

Monitoring of soluble HLA class I size variants after liver transplantation.

To monitor soluble HLA class I (sHLA-I) and their size variants after liver transplantation (LTX) plasma samples from 22 LTX patients were studied by sHLA-I ELISA, SDS-PAGE, and densitometry. Samples collected were classified into three groups: Group 1 comprised samples taken during episodes without complications, group 2 during episodes of cholangitis/cholestasis (CC), and group 3 during episodes of acute rejection (AR). Compared to group 1 (0.27 +/- 0.03 SEM microg/ml) mean sHLA-I increments in groups 2 and 3 were with 0.53 +/- 0.05 SEM microg/ml and 0.47 +/- 0.04 SEM microg/ml increased (p < 0.001). The same samples were studied by SDS-PAGE and the 43, 39, and 35 kD sHLA-I variants were quantified densitometrically. In samples of group 1 ratios of 43 vs. 39 kD bands revealed a mean of 2.1 +/- 0.3, whereas in group 2 and 3 these were only 0.8 +/- 0.1 SEM and 0.9 +/- 0.1 SEM, respectively, (p < 0.001). For the relation between 43 and 35 kD variants a reduced ratio of 1.1 +/- 0.2 SEM was confined to group 3 samples (p < 0.001), as groups 1 and 2 had ratios of 13.4 +/- 2.3 SEM and 8.4 +/- 2.9 SEM, respectively. This indicates that elevated sHLA-I levels during CC or AR are mainly caused by increases of 39 and/or 35 kD sized molecules. Therefore, our study demonstrates, that after LTX the contribution of sHLA-I size variants to total sHLA-I amounts changes drastically during immune activation pointing to different mechanisms of sHLA-I release.

Acute Disease↗