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Biomedical subjects

C Brautbar

Publications and source records attributed to C Brautbar.

At least 127 records · Page 7Linked to original sources

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor alpha-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.

Amino Acid Sequence↗

Zonal variation of HLA expression on human cornea epithelium.

Seven human corneas were studied, using the enzyme-linked immunosorbent assay (ELISA) technique, for expression of human leukocyte antigens (HLA) class-I and class-II antigens on the epithelial cells of the central 8-mm corneal button and the remaining corneal periphery and limbus. The antigenicity was compared with that of Raji and Daudi cell lines, which served as controls. It was demonstrated that the epithelium of the two corneal parts shows a high expression of HLA class-I antigens, albeit not as strong as that found in the control cell lines. On the other hand, HLA class-II antigens were found only in the limbal-peripheral area. Expression of the HLA class-I antigens was weaker in the central portion of the cornea. It is proposed that the absence of HLA class-II antigens expression in the central portion of the cornea offers an additional explanation for the greater success of small corneal grafts, since the recognition step necessary for the immunological response is lacking.

Adolescent↗

HLA antigens in patients with Heberden's nodes.

Tissue typing was performed on a group of 51 patients with Heberden's nodes (HN) (45 Ashkenazic and 6 non-Ashkenazic Jews). The frequency of HLA-DR2 was higher (P = 0.03) in the Ashkenazic patients than in the Ashkenazic controls. However, the association was not significant after correction for the number of tested alleles at that locus. In the second part of the study, HLA typing was performed on subjects from a family with multiple HN occurrences. Of the 13 family members typed, 9 had HN: 6 of these had the haplotype A2, Bw35, DR2. We conclude that the development of HN may be influenced by genetic factors. Our results may suggest an association between HN and HLA-DR2 in Ashkenazic Jews.

Female↗

HLA and schizophrenia in Israel.

Thirty-two Israeli Jewish schizophrenic patients were typed for Class I (HLA-A, B, C) and Class II (HLA-DR) antigens. A significant increase of HLA-A2 (P = 0.01) and A23 (P = 0.02) was found. None of the 10 HLA-DR antigens tested was associated with the disease. Study of eight families indicated that close linkage of the gene responsible for this disorder to the HLA system is unlikely.

Adult↗

HLA-B51 may serve as an immunogenetic marker for a subgroup of patients with Behçet's syndrome.

Epidemiologic data, family history, clinical data, HLA typing, neutrophilic chemotaxis, and immunofluorescence of clinically normal non-sun-exposed skin were studied in 46 Israeli non-Ashkenazi Jewish and Arab patients with Behçet's syndrome. HLA-B51 was present in 71 percent of the patient group as compared with 13 percent of the control group (relative risk = 17.1). In four of 30 families in the B51-positive group, there was a close relative of the proband with Behçet's syndrome who was carrying the HLA-B51 antigen. Neutrophilic chemotaxis in this group was enhanced in 80 percent of the patients, and in most patients no deposition of immunoglobulin in the dermo-epidermal junction was observed, whereas C3 was present in papillary vessels. In the B51-negative group, the family history was negative for Behçet's syndrome, neutrophilic chemotaxis was enhanced in only two of eight patients, and in four of six patients, IgM deposition was detected in the dermo-epidermal junction. It is concluded that in Israeli non-Ashkenazi Jews and Arabs, there is a significant association between HLA-B51 and the risk of developing Behçet's syndrome. The B51-positive patient group has a family history of the disease, enhanced neutrophilic chemotaxis, and a lack of immunoglobulin deposition in the dermo-epidermal junction.

Behcet Syndrome↗

HLA-Dw clusters associated with DR4 in Israeli Jews and the definition of a new DR4 associated Dw subtype: Dw"SHA".

A homozygous typing cell (HTC), that identifies a newly defined HLA-Dw determinant Dw"SHA," is described. The donor of the HTC was a Yeminite Jew and an offspring of first cousin marriage. This cell is not included in the known DR4-associated specificity clusters Dw4,Dw10,Dw13,Dw14,Dw15, or the provisional cluster Dw"KT2." Dw"SHA" was shown to segregate with DR4 positive haplotypes in family analysis, and in a population study was present in three of 43 unrelated DR4 positive individuals. This new Dw determinant was detected in Israeli Jews of Yemenite origin bearing the haplotype HLA-Bw41,DR4,DQw3. This indicates that Bw41,DR4,DQw3,Dw"SHA" may represent a typical allele combination in Yemenite Jews. Among 43 DR4 haplotypes in Israeli Jews, Dw10 had the highest antigen frequency (41.8%), whereas in American Caucasoids and in Japanese, Dw4 and Dw15 were most frequent, 44% and 40.5%, respectively.

Asian People↗

Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines.

Epstein-Barr virus (EBV)-carrying Burkitt lymphoma (BL) cells are relatively or completely resistant to the lytic effect of major histocompatibility complex class I HLA antigen-restricted cytotoxic T lymphocytes (CTLs) generated by stimulating lymphocytes of EBV-seropositive donors with the autologous EBV-transformed lymphoblastoid cell line (LCL). We previously found that EBV-negative and EBV-carrying BL lines derived from HLA-A11-positive donors were not only resistant to lysis by the HLA-A11-restricted CTL generated by stimulation with the autologous LCL, but also to HLA-A11-specific CTL derived from lymphocytes of an EBV-seronegative donor stimulated with an allogeneic LCL. Using the same and additional cell lines, we now show that the CTL resistance of the BL lines is probably due to a selective down-regulation of HLA-A11. We also show that the EBV-encoded latent membrane protein is expressed at a lower level in the EBV-carrying BL lines than in EBV-transformed LCLs. Only one of eight in vitro EBV-converted BL lines that shifted to a more LCL-like growth pattern expressed LMP at a high level. This line also reexpressed the HLA-A11 antigen that was undetectable in its EBV-negative progenitor. Our findings suggest that the typical BL cell phenotype is associated with low expression of both proteins.

Antigens, Neoplasm↗

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

Pemphigus vulgaris in Israeli Ashkenazi and non-Ashkenazi Jews and in Austrian non-Jewish patients is strongly associated with the DR4 and DRw6 alleles of the HLA-D region class II genes. Restriction fragment length polymorphism analysis was undertaken with DQ beta, DQ alpha, and DR beta cDNA probes. Hybridization with the DQ beta probe identifies Pvu II, BamHI, and EcoRV fragments that absolutely discriminate pemphigus vulgaris patients from healthy DR-, DQ-, and ethnic-matched controls. In contrast the DQ alpha and DR beta probes failed to identify disease-specific restriction fragment length polymorphism fragments. These studies indicate that DQw1 and DQw3 polymorphisms carried by pemphigus vulgaris patients may be directly involved in predisposition to the disease or may be tightly linked to the susceptibility gene itself. To our knowledge, this is the first example of an HLA restriction fragment length polymorphism that is highly associated with susceptibility to autoimmune disease.

Alleles↗

Analysis of the antigen specific helper T cell function and HLA-DR of Israeli patients with rheumatoid arthritis (RA).

Forty-three patients with rheumatoid arthritis (RA) were studied for their ability to respond to the synthetic polypeptide antigen (T, G)-A-L as measured by the production of a T cell helper factor by their antigen activated T cells. Sixteen patients (37%) responded to (T, G)-A-L by the production of an antigen specific helper T cell factor, a percentage not significantly different from healthy donors. The production of antigen specific T cell helper factors was affected, although not significantly, by immune modulating drugs and by the presence of rheumatoid factor in sera of patients. The high incidence of HLA-DR 4 reported for RA patients was not observed in this group of RA patients.

Adult↗

Human leukocyte antigens (HLA) class I and class II on sperm cells studied at the serological, cellular, and genomic levels.

The expression of human leukocyte antigens (HLA) on highly purified human ejaculated sperm cells was studied using the sensitive enzyme-linked immunosorbent assay (ELISA) technique and a wide panel of monoclonal antibodies to class I and class II HLA. In addition, the stimulatory capacity of these cells was tested in mixed cultures of lymphocytes and spermatozoa, and the levels of RNA homologous to the HLA class I and class II genes were determined. The results obtained using the ELISA indicate that the class I and class II HLA serologically defined antigens are weakly expressed on the cell surface of the mature spermatozoa. Highly purified sperm cells consistently stimulated heterologous lymphocytes but not when HLA-DR compatibility was observed between stimulator and responder. The proliferative response of lymphocytes induced by sperm cells was lower than the response obtained in a lymphocyte-lymphocyte combination, though the kinetics of the response were similar in both cases. In addition, it was found that spermatozoa contained RNA species homologous to HLA class II DR beta and DQ beta genes sequences but not to HLA class I sequences. The levels of these RNA species were significantly reduced after interferon stimulation. Lymphocytes that served as positive control were found to contain RNA complementary to both HLA class I and class II genes.

Antibodies, Monoclonal↗

Human leukocyte antigen (HLA) DR4. Positive association with rapidly progressing periodontitis.

The relationship between human leukocyte antigens (HLA) determinants and periodontitis has been examined by several authors without showing any particular pattern. However, no study has investigated the HLA-D determinants, which are generally associated with immune disorders, and rapidly progressive periodontitis (RPP). The HLA profile of 10 RPP patients was compared with that of a healthy control population (n = 120). Although no significant difference was found for HLA-A, HLA-B, and HLA-C, HLA-DR4 of the HLA-D group was found in 80% of patients but only in 38.3% of controls. A high frequency of HLA-DR4 has been reported in rheumatoid arthritis (RA) patients. This finding may be significant in light of previous reports highlighting similarities between RA and periodontal disease.

Adult↗

Absence of HLA linkage in familial hypogonadotropic hypogonadism.

In a family with five daughters, three suffered from primary amenorrhea. The diagnosis of familial idiopathic gonadotropin deficiency (FIGD) was established. The entire family underwent HLA evaluation, and no linkage between the HLA and FIGD was found.

Adolescent↗

Differential recognition of tumor-derived and in vitro Epstein-Barr virus-transformed B-cell lines by fetal calf serum-specific T4-positive cytotoxic T-lymphocyte clones.

Two interleukin-2 (IL-2)-dependent cytotoxic T-cell clones were obtained by limiting dilution from a lymphocyte culture stimulated in vitro with the autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) in the presence of fetal calf serum (FCS). Both clones uniformly had a T3+, T4+, Dr+ phenotype and lysed autologous B blasts, the autologous LCL, and allogeneic B cell lines sharing major histocompatibility complex (MHC) class II antigens. The cytotoxic function was triggered by FCS-derived components. There was no killing if the sensitive targets were cultured in serum-free medium or in medium supplemented with human serum. Sensitivity to lysis could be restored by exposing the targets to FCS for at least 6 hr at 37 degrees C. Monoclonal antibodies directed to T-cell-specific surface antigens and MHC class II antigens inhibited lysis with different efficiencies depending on the target cell origin. Killing of Burkitt's lymphoma (BL)-derived cell lines was blocked more easily than killing of LCLs. LCLs but not BL lines induced proliferation of the T-cell clones in the absence of exogenous IL-2. The differences were not related to quantitative variations in the expression of MHC class II antigens, indicating that BL lines differ from LCLs in other cell membrane properties that may influence antigen presentation. The results suggest that the affinity of effector/target binding, which is probably influenced by the concentration of antigenic determinants expressed on the target cell membrane, determines whether proliferative responses or cytotoxicity are induced in the antigen-recognizing T cells.

Antibodies, Monoclonal↗