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Biomedical subjects

C Brautbar

Publications and source records attributed to C Brautbar.

At least 91 records · Page 5Linked to original sources

Molecular analysis of HLA-B27 haplotypes in Caucasoids. Frequencies of B27-Cw in Jewish and Spanish populations.

PCR in combination with SSO probes was used to analyze the polymorphism in exons 2 and 3 of HLA-B27 subtypes and HLA-C-related alleles in two genetically distant Caucasian groups: Spanish and Jewish populations. AS patients and healthy B27 donors from both populations were analyzed in order to ascertain B27-Cw haplotypes. Three different ancestral haplotypes were found to be represented in both populations: B*2705/Cw*0102, B*2705/Cw*02022, and B*2702/Cw*02022. The B*2705 (92.5%) was the most frequent allele found in the Spanish population, carried by B*2705/Cw*0102 (60.9%) and B2705/Cw*02022 (30.4%) haplotypes. In contrast, B*2702 (59.4%) was the most prevalent allele found in the Jewish population and was carried by the B*2702/Cw*02022 (63.3%) haplotype. No different allelic and haplotypic distributions were among healthy and AS patients in either Spanish or Jewish populations. The differences found in the distribution of B27 haplotypes among Spanish and Jewish Caucasian populations are consistent with the genetic distance of these ethnic groups. When the Jewish population was subdivided into Ashkenazi (A) and non-Ashkenazi (NA) groups, no significant differences were observed in the distribution of B*2702/Cw*02022 haplotype. Minor differences were observed in the underrepresented B*2705 haplotypes. The present results reflect the ancestral affinities of A and NA Jewish populations. A possible HLA-B27 evolutive pathway in Caucasians is proposed according to the data available for the B27/Cw ancestral haplotypes in Spanish and Jewish groups.

Base Sequence↗

Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?

BACKGROUND: Psoriasis vulgaris was reported to be associated with a specific alanine residue at position 73 of HLA-C alleles in Japanese patients. OBJECTIVE: Our purpose was to determine the role of HLA genes in susceptibility to psoriasis vulgaris in the Israeli Jewish population. METHODS: Twenty-eight Israeli patients were analyzed for their HLA class I and II specificities by means of serologic and molecular methods. RESULTS: All patients possessed in their HLA-C antigens an alanine residue at position 73 (p < 0.002). A significantly increased frequency of HLA-Cw6 and of Cw7 was also observed among the patients (p < 0.02). CONCLUSION: Our study clearly shows that alanine in position 73 is significantly associated with psoriasis vulgaris in Jewish patients. Cw6 and Cw7 have a unique antigen-binding pocket containing both alanine at position 73 and a negatively charged aspartic acid at position 9. These residues are most probably important in determining the conformation of the C pocket and in turn the nature of the peptide bound to it. We suggest that this combination confers the highest risk of the development of psoriasis vulgaris.

Alanine↗

Serologic and molecular analysis of the HLA system in Israeli Jewish patients with oral erosive lichen planus.

Oral erosive lichen planus is a distinct subtype of the common dermatosis lichen planus. Although the etiology of lichen planus is still obscure, it is known that cell-mediated immune mechanisms and genetic factors underlie its pathogenesis. Previous studies have found an association between lichen planus and HLA-DR3 or DR9 in different population groups. The present work was designed to elucidate, at the serologic and molecular levels, whether and which HLA genes are associated with oral erosive lichen planus in Israeli Jewish patients. A significant association with HLA-DR2 (RR = 4.7; pc < 0.0013) and a decrease in DR4 (RR = 0.3; p < 0.03) among the patients were noted. Oligotyping of DR2 alleles showed the presence of all three common variants (DRB1*1501, DRB1*1502 and DRB1*1601) in the patients, although none of the variants was overrepresented significantly. Three possible explanations for the role of HLA genes in the predisposition to oral erosive lichen planus are discussed. The most attractive theory for the pathogenesis of the disease seems to include the involvement of non-classical HLA genes.

Female↗

Sequential manifestation of different forms of early-onset periodontitis. A case report.

Pathogenic bacteria constitute the primary extrinsic agent in the etiology of early onset periodontitis. However, the risk of developing periodontal disease is not equal for all individuals, suggesting host factors are involved in determining an individual's disease susceptibility. In this report, a case of an otherwise healthy female, who exhibited prepubertal periodontitis (PPP) at age 10, juvenile periodontitis (JP) at age 13, and rapidly progressive periodontitis (RPP) at age 29 years, is presented. Microbial, immunological, and genetic features of the case are presented. PPP, JP, and RPP are considered distinct disease entities, albeit with similar pathology and pathogenesis, yet all were manifest sequentially in the same individual. This report presents the idea that certain individuals are predisposed to early-onset periodontal diseases and the early identification of risk factors is important in the management of these individuals.

Adolescent↗

HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the predominant HLA-DR1 subtype.

Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Invasive squamous cell carcinoma of the cervix: is HLA-DQ a disease marker in Jewish patients?

HLA class I and class II were investigated in 30 Israeli patients with invasive squamous cell carcinoma of the cervix and compared to healthy controls. None of the studied serological specificities were found to be associated with the disease. Genomic DNA from the patients was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known DQA1 and DQB1 allelic variants. Fifteen out of the 30 patients tested (50%) were found to carry the DQA1*0501 allelic variant, which is common in the local healthy population (67%). DQB1*0302 was found in eight out of 30 patients (27%) while this allele was present in 17% of the healthy population, a difference which is not statistically significant. Our data indicate that there is no apparent association between invasive squamous cell carcinoma of the cervix and the HLA antigens and alleles studied including the alleles of the DQA and DQB loci in the Israeli population. Our findings indicate that MHC genes could not be useful in the diagnosis of squamous cell carcinoma of the cervix.

Alleles↗

Sclerosing cholangitis associated with Crohn's disease and autoimmune haemolytic anaemia.

A middle-aged man was found to have autoimmune haemolytic anaemia. Seven years after the first manifestations of the anaemia, he developed jaundice without haemolysis and a diagnosis of primary sclerosing cholangitis was made by endoscopic retrograde cholangiography. Crohn's colitis was later confirmed by X-rays and colonoscopy. This association is unique to the best of our knowledge and suggests that genetic and immunological mechanisms may be involved in the pathogenesis of these diseases.

Adult↗

Adoptive transfer of immunity to hepatitis B virus after T cell-depleted allogeneic bone marrow transplantation.

Recipients of allogeneic bone marrow transplantation are pancytopenic for several weeks and immunosuppressed for many months as a result of myeloablative therapy required to eliminate the basic disease and to prevent allograft rejection. After bone marrow transplantation, these patients remain profoundly immunosuppressed by the chemotherapy and immunotherapy used as prophylaxis against graft-vs.-host disease, treatment of established disease or both. These patients are usually dependent on multiple blood products and are therefore at risk for hepatitis B virus infection, which may run a fulminant course. Active immunization against hepatitis B virus in the immediate pre-bone marrow transplantation and post-bone marrow transplantation periods was found to be ineffective, probably because of the absence of T cell-dependent B-cell responses, which persists for approximately 1 yr after bone marrow transplantation. We studied adoptive transfer of immunity to hepatitis B virus through bone marrow transplantation in two populations of patients. The first group (A) consisted of 12 pairs of BMT donors and recipients, in which all bone marrow donors were positive for antibodies to HBc and HBs as a result of previously acquired hepatitis B virus infection and resolution; all recipients were negative to antibodies to HBc and HBs. The second group (B) consisted of eight pairs of donors and recipients in which all the donors were actively immunized against hepatitis B virus before bone marrow transplantation; all recipients were negative for all hepatitis B virus markers. All bone marrow transplantation recipients were monitored for antibodies to hepatitis B virus antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Serological and molecular analysis of HLA in Israeli primary sclerosing cholangitis patients.

HLA class I and class II were investigated in 15 Israeli primary sclerosing cholangitis patients and compared to healthy controls. None of the well established serological specificities were found to be associated with the disease. HLA-DR52 is serologically defined, but its subtypes DR52a, DR52b, and DR52c cannot be precisely defined by serological means. Therefore, we have used HLA-DNA typing in order to assign the DR52 splits in PSC patients. Genomic DNA was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known HLA-DR52 associated alleles. Only 4 out of the 15 PSC patients tested were found to express DRB3*0101 the allele that encodes DR52a. Of the remaining 11 patients, 9 expressed DRB3*0202 haplotypes, with 2 patients expressing both DRB3*0101 and DRB3*0202, and the remaining 2 patients expressed no DRB3 allele. Our data indicate that there is no apparent association between PSC and the HLA antigens and alleles studied including the alleles of the DRB3 locus in the Israeli population. Thus HLA pheno/genotyping of PSC patients in the Israelis will not be useful for early and/or differential diagnosis of this disease.

Alleles↗

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles↗

Familial erythema nodosum.

Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented.

Acute Disease↗

A short human and mouse MLR assay utilizing lymphokine (IL-2, IL-3) secretion as an early activation event.

The mixed leukocyte reaction is the only functional in vitro assay currently employed for confirmation of MHC matching between bone marrow recipients and their prospective donors and for MHC class II (HLA-Dw) typing. This assay is, however, time-consuming (6 days for human MLR), whereas for clinical purposes results are often required much earlier. In an attempt to shorten the MLR incubation period, we tested IL-2 (in human MLR) and IL-2/IL-3 (in mouse MLR) production as an indication of early stages of T cell activation. We here describe a shorter assay in which IL-2 and IL-3 secretion during MLR was assessed by adding the respective lymphokine-dependent cell lines either to the MLR supernatants or directly to the original MLR cultures, using the colorimetric (3-[4,5 Dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) (MTT) technique or the 3H-thymidine incorporation assay. In both human and mouse MLR systems, lymphokine production peaked at 24-48 hr after culture initiation, allowing tests to be completed within 48 to 72 hr. Weak MLR responses, as detected by lymphokine production, could be considerably amplified by irradiating (250-1000 cGy) the responder cells and by adding heparin (1-10 U/ml) to the cultures. The results obtained by this novel procedure correlated with those obtained by the standard 6-day human MLR assay in over 250 combinations tested thus far, and therefore it may replace the standard MLR procedure.

Animals↗

HLA antigens in subacute sclerosing panencephalitis patients in Israel.

HLA Class I antigens were determined in the 49 subacute sclerosing panencephalitis (SSPE) patients. In analyzing the Arabs and the Jews separately, there is a decrease in HLA-A2 in the Jewish patients (X2 = 3.96; P less than 0.05), a significant increase in the HLA-A29 in the Arab SSPE patients (X2 = 6.29; P less than 0.02), and a slight, insignificant increase of HLA-A29 in the Jewish patients. The present study supports previous findings of Kurent's and needs following studies in larger groups of Arab SSPE patients.

Child↗

Regulatory T cell activity specific to human type II and III collagens in rheumatoid arthritis.

Fifty-one patients with rheumatoid arthritis (RA) were examined for their immune response potential to human collagen type II and III. It was found that T cells of 57% of patients with RA proliferated to collagen type III whereas only 27% of T cells of patients with osteoarthritis (OA) and healthy controls responded to this antigen by proliferation (p less than 0.04). A lower percentage (38%) of patients with RA had proliferative responses to collagen type II in comparison to 17% of responders in healthy controls. The capability to produce T cell helper factors specific to collagen type III was found to be significantly higher in patients treated with nonsteroidal antiinflammatory drugs (NSAID) (60%) in comparison to patients with OA (16%) and healthy controls (13%). Immunoregulatory drugs affected the specific T helper function in response to collagen type III but did not change the proliferative responses to collagen type II and III in patients with RA. HLA analyses revealed a significant difference in the frequency of HLA-DRw10 between our sample of patients with RA and healthy controls.

Antibody Formation↗