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Results for “HLA class II”

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At least 1,063 records · Page 59Linked to original sources
PubMed1998

HLA class I and class II expression of pulmonary adenocarcinoma cells and the influence of interferon gamma.

BACKGROUND: The clinico-biological significance of HLA (both class I antigen and class II one) expressed on tumor cells still remains controversial. METHODS: Tumor cells were freshly separated from 33 surgical specimens of pulmonary adenocarcinoma. The tumor cells were incubated for 24 h in the presence or absence of IFN-gamma (130 International Units/ml). After incubation, the cells were cytocentrifuged onto glass slides and immunostained with either an anti-HLA class I (A, B, C) monoclonal antibody or anti-HLA class II (DR) one. RESULTS: In 22 of 33 cases (66.7%), the HLA class I were individually expressed by more than 60% of tumor cells while so were the HLA class II in 15 (45.4%). No significant correlation was observed between the HLA class I expression and the HLA class II one. The proportion of HLA class I-positive tumor cells correlated with neither the grade of histological differentiation nor the stage of disease. In contrast, the proportion of HLA class II-positive tumor cells correlated with both the grade of histological differentiation and the stage. In most cases, IFN-gamma was found to increase the proportion of class II-positive tumor cells as well as that of class I-positive cells. CONCLUSIONS: The above findings thus suggested that the HLA class II expression might therefore represent a manifestation of cellular differentiation and that IFN-gamma may, as a result, have the potential to differentiate cancer cells.

Adenocarcinoma↗
PubMed2000

The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs.

A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles. Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1. While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles. Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1. This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant.

Alleles↗
PubMed2003

HLA class II alleles and genetic predisposition to the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL). Its etiology is linked to genetic predisposition, which is accounted for, at least in part, by genes of major histocompatibility complex (HLA system). The association of APS with human leukocyte antigen (HLA) alleles is a consequence of the association of aPL with HLA alleles. Some HLA alleles carry the risk to produce aPL, and this is independent of the clinical context. In fact, we find the same associations between HLA and aPL in primary APS and in APS secondary to systemic lupus erythematosus (SLE). The association of HLA-DR4, -DR7, -DRw53 and -DQB1*0302 with aCL that has been demonstrated in primary APS can also be found in SLE, a disease with a completely different pattern of HLA allele association (DR2, DR3, DRw52). In addition, the various aPL (anticardiolipin antibodies, lupus anticoagulant, anti-beta2GPI antibodies, antiphosphatidylserine/prothrombin antibodies) show similar HLA association, again independent of the clinical context (primary APS or SLE), and across various ethnic groups.

Alleles↗
PubMed2001

Transmission disequilibrium analysis of HLA class II DRB1, DQA1, DQB1 and DPB1 polymorphisms in schizophrenia using family trios from a Han Chinese population.

Our goal was to evaluate the role of HLA in the risk of developing schizophrenia, in a Han Chinese population. In several Japanese studies, there is evidence of association with DR1 and schizophrenia. A variety of other associations have been reported in other populations, including negative associations with DQbeta(*)0602 and positive associations with DR1(*)0101. Using sequence specific oligonucleotides, we genotyped four HLA markers (DRB1, DQA1, DQB1 and DPB1) in 165 family trios, consisting of Han Chinese schizophrenic subjects and their parents. Individual markers were analysed for transmission distortion in the trios using the transmission disequilibrium test. Multiple haplotype transmission was performed using the program TRANSMIT v2.5. The four markers were in strong linkage disequilibrium with each other (P value from 0.002 to 0). There was no evidence of overall transmission disequilibrium for each of the four loci. For DRB1, we did not find transmission distortion for the DRB1(*)04 and DRB1(*)08 alleles, as reported previously, but the DRB1(*)03 allele was preferentially not transmitted (P=0.009), and the DRB1(*)13 allele was preferentially transmitted from parents to schizophrenic offspring (P=0.041). Using haplotypes of pairs of markers, a significant global P value of 0.019 was achieved when using DRB1 and DQA1, mainly as a result of the excess transmission of DRB1(*)13-DQA1(*)01 (P=0.012) and a deficit in transmission of DRB1(*)03-DQA1(*)05 (P=0.002). In summary, we did not confirm any of the specific HLA allelic associations reported previously in Japanese or other populations. However, our results are compatible with the view that this region of HLA might contain a susceptibility gene which is in linkage disequilibrium with DRB1 and DQA1 genes.

Adolescent↗
PubMed1994

Expression of HLA-class II antigen in gastric carcinomas. Its relationship to histopathological grade, lymphocyte infiltration and five-year survival rate.

To investigate whether the expression of HLA-DR antigen in gastric carcinomas is associated with the survival rate, we studied 70 cases of gastric carcinoma using a monoclonal antibody. Forty-seven cases (67%) stained positively, including 31 differentiated carcinomas, and 16 undifferentiated carcinomas. A close correlation was found between expression of HLA-DR antigen and differentiation of the tumor cells. Marked lymphocyte infiltration was seen in the HLA-DR antigen positive cancers. In advanced gastric cancers, the 5-year survival rate of patients with HLA-DR antigen positive cancers was significantly higher (67.5%) than that of patients with HLA-DR antigen negative cancers (40%). The data suggest that the expression of HLA-DR antigen in gastric carcinomas may reflect the degree of tumor cell differentiation, and influence the host immune response and prognosis.

Carcinoma↗
PubMed2005

Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies.

OBJECTIVE: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. DESIGN AND METHODS: Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed. RESULTS: No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.

Adolescent↗
PubMedDate not supplied

A novel HLA class II molecule (DR alpha-DQ beta) created by mismatched isotype pairing.

Human major histocompatibility complex (MHC) class II molecules are heterodimeric glycoproteins composed of non-covalently associated alpha and beta chains. Only isotype-matched alpha-beta associations have been described in man; these can occur either by cis- or trans-complementation (HLA-DR, DQ, DP). Here evidence is provided for the existence of a new type of hybrid molecule (DR alpha-DQ beta) arising by mixed-isotype pairing in human B-cell lines. Class II isotype-mismatched heterodimers have been recently reported in the mouse after transfection of class II genes, and our data demonstrate that such interisotypic pairing can occur in untransfected cells. This crosspairing greatly enhances the repertoire of the class II antigens that regulate immune responses and leads us to reconsider the HLA-disease association.

Antibodies, Monoclonal↗
PubMed1990

Are soluble monocyte-derived HLA class II molecules candidates for immunosuppressive activity?

Supernatants of human blood monocyte cultures suppressed PHA responses (IL-2 synthesis, IL-2R expression, DNA synthesis) of autologous and allogeneic lymphocytes. The main suppressive activity was found in the 65-kDa (and 23-kDa) range. It could be incompletely neutralized by mAb specific for a non-polymorphic HLA DR determinant and could also be adsorbed to and eluted from an anti-DR immunoabsorbent column. On blots of monocyte lysates and monocyte culture supernatants, the mAb RoDR recognized antigens of nearly the same Mr. The hypothesis that soluble HLA DR alpha beta heterodimers or beta chains are likely candidates for the suppressor factor was confirmed by analogous effects of purified HLA DR molecules. We favor a model in which soluble MHC class II molecules (in contrast to surface-bound ones) may interfere with the association and cross-linking processes necessary for T cell activation by competing for CD4 binding sites.

Antibodies, Monoclonal↗
PubMed1991

HLA class II induction by interferon-gamma in K562 variant cell line: inhibition by serum lipid.

The induction of class II antigen (Ag) by interferon-gamma (IFN-gamma) in variants of the K562 cell line has been examined in this study. Following incubation of K562A cells with IFN-gamma, surface expression of HLA-DR molecules was demonstrated by indirect immunofluorescence, confirmed by immunoblotting, and HLA-DR3 Ag specificity identified. HLA-DP and HLA-DRW52 Ag were co-expressed, but no HLA-DQ expression occurred. A variant of this line, designated K1A, spontaneously developed resistance to IFN-gamma induction of class II Ag, but continued to express class I Ag. In a third K562 variant, designated K562B, no class II gene products could be induced. Northern blot analysis indicated that mRNA levels correlated with surface class I and II Ag expression in all of the K562 cell lines. Resistance to IFN-gamma inducible class II Ag expression in K1A cells did not involve changes in IFN-gamma receptor affinity or number but was shown to be due to an inhibitory effect of serum lipid. These results indicate that cells derived from a common parental line may differ in susceptibility to a regulatory mechanism affecting IFN-gamma inducible class II Ag expression.

Blotting, Northern↗
PubMed1999

[Extensive HLA class II studies in Chinese narcoleptic patients].

OBJECTIVE: Narcolepsy is a debilitating, lifelong sleep disorder. Its familial occurrence suggests that genetic factors may be of importance in the etiology. Narcolepsy is a very rare disease among Chinese, thus it was of interest to study the association of narcolepsy with the HLA system in Chinese narcoleptic patients. METHODS: To explore the role of HLA-DRB genes in the development of narcolepsy, we studied 10 narcoleptic patients and 50 race matched controls in whom HLA-DR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP). RESULTS: All narcoleptic patients were found to be of DRB1 * 1501 and DRB5 * 0101 genotype. CONCLUSION: These results indicate that HLA-DRB1 * 1501 is a better primary candidate susceptibility gene for narcolepsy in Chinese.

Adult↗
PubMed1996

Liposome-mediated transfer of genes containing HLA-class II alpha chain into cultured embryonic chick cardiac myocytes and COS7 cells.

Rejection remains a major problem after cardiac transplantation. One hypothesis is that transfer of recipient HLA genes could lead to expression of the antigens on the surface of donor cells and so facilitate graft acceptance. This paper describes a pilot study for relevant gene-transfer (transfection) experiments on adult cardiac myocytes, investigating the feasibility of transfection using cationic liposomes. The plasmid pcDV1-pL2 vector containing HLA-DR-alpha chain gene was incubated with Lipofectin, a DOTMA and DOPE lipid mixture, for 10 minutes. Embryonic chick cardiac myocytes (ECCM) and COS7 monkey cells were incubated with DNA: Lipofectin ratios of 1:1, 1:2, 1:4, and 1:10 for 16 hours (hrs). Using a fixed ratio of 1:4, incubation periods of 4, 8, and 16 hrs were compared. Finally, cells were incubated for 16 hrs and consecutively cultured for 6 days. Expression of the HLA-DR-alpha chain antigen was detected by indirect immunohistochemical staining. Highest transfection rates were achieved with a DNA: Lipofectin ratio of 1:4 for ECCM and COS7 cells (2.7% +/- 0.6% and 2.4% +/- 0.3% after 16 hrs incubation) and a transfection time of 4 hrs (5.8% +/- 0.6% and 5.3% +/- 1.7%). Immunohistochemically positive cells were present after 6 days (2.0% +/- 1.2% and 2.1% +/- 0.3%). We found a low level of expression of HLA-DR-alpha chain gene, influenced by transfection time and DNA: Lipofectin ratio. To increase the efficiency of liposome-mediated gene transfer and assess potential applications in cardiac transplantation, further investigation of cell properties promoting transfection is necessary.

Adult↗