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Biomedical subjects

C Brautbar

Publications and source records attributed to C Brautbar.

At least 163 records · Page 9Linked to original sources

Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1).

A new monoclonal rat anti-human lymphocyte antibody (CAMPATH-1) which lyses cells with autologous human complement was used for depletion of T lymphocytes from human bone-marrow allografts in vitro before transplantation in 11 high-risk patients. HLA-matched siblings were used as marrow donors. T-cell depletion was substantial when measured by E-rosette formation (0-0.18% residual T cells) and immunofluorescence with a monoclonal anti-T-cell antibody (0-0.5%). No anti-graft-versus-host disease prophylaxis was given after transplantation. Rapid engraftment was reported in all patients, and the post-transplantation course was uneventful. No signs of graft-versus-host disease developed in any of the patients, who were observed for a maximum period of 12 months. The method might be suitable for larger-scale studies in high-risk patients. The late graft failure seen in 2 patients may reflect residual host resistance uncompromised by GvHD.

Adolescent↗

Familial hereditary thrombocytopenia and HLA.

Three generations of a Jewish family with hereditary thrombocytopenia (HT) are described. The disease was manifested clinically by mild bleeding tendency since infancy. Circumcision, however, did not result in excessive bleeding. HLA study in this family indicated that the HT locus is not linked to HLA.

Adult↗

Genetic polymorphisms among Bukharan and Georgian Jews in Israel.

Bukharan and Georgian Jews have lived in central Asia for many centuries. Approximately 30,000 Bukharan and 37,000 Georgian Jews lived in their respective countries within the USSR between 1920 and 1960. Genetic markers of blood--blood groups, isoenzymes, HLA antigens, and gamma and kappa chain allotypes--were tested in blood samples from 113 Bukharan and 134 Georgian Jews living in Israel. Estimates of inbreeding were low: alpha = 0.0088 for Bukharan and alpha = 0.0011 for Georgian Jews. G6PD deficiency was relatively rare in Bukharan (2.2%) and in Georgian Jews (6.0%), when compared to other Jews in the area. Both populations showed frequencies of some markers similar to that of other Jewish populations, but frequencies of several markers were extremely high or low. Bukharan Jews showed very high frequencies of B(0.243), cDe (0.122), JkA (0.705), HLA-A29 (0.167), A30 (0.116) and B7 (0.124), and AcPA (0.451) and very low ones of O(0.518), CDe(0.422), AcPB (0.513) and GLO1 (0.140). Very high frequencies in Georgian Jews were observed for cDE (0.189), HLA-A3 (0.194), Bw35 (0.300) and GLO1 (0.367). Yet the greatest difference between both populations was in African characters. While in Bukharan Jews Fy was very frequent (0.146) and cDe was the highest observed among Jews (0.122), neither of these markers was detected among the Georgian Jews tested. Yet, another African character, the Gm1,5,10,11,13,14,17,26 haplotype, occurred in both populations (0.028 and 0.042 in Bukharan and Georgian Jews, respectively). Distance measures for Bukharan, Georgian, Iranian, Cochin, and Libyan Jews based on 13 polymorphic loci showed the greatest distance between Cochin Jews and the other populations and the smallest distance between the Georgian and Iranian Jews.

Blood Group Antigens↗

HLA-Dw"SHY": a new lymphocyte defined specificity associated with HLA-DRw10.

HLA-DRw10 is a relatively new class II serologically-defined alloantigen first described in the 8th International Histocompatibility Workshop. To date the HLA-Dw related to the DRw10 specificity has not been detected. We have studied a Jewish family ("SHY") of Yemenite origin, in which the parents are first cousins who share one HLA haplotype: A29,Cw2,B7,BfF,DRw10,GL02. Two of the offspring in this family are homozygous for this haplotype. MLC family study confirmed that each of the two individuals was homozygous for HLA-Dw. No currently defined HLA-Dw specificity could be assigned to "SHY" using a selected panel of Caucasoid and local HTcs. HLA-Dw"SHY" was shown to segregate with DRw10 positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated individuals. HTC"SHY" thus expresses the first HLA-Dw specificity associated with DRw10.

Epitopes↗

Maternal-paternal histocompatibility: lack of association with habitual abortions.

Class I human leukocyte antigens (HLA-A, -B) and class II (HLA-DR) antigens were determined in 60 and 30 carefully selected couples with multiple abortions, respectively. The study group was compared with fertile couples with no history of abortion and with a control group consisting of randomly matched women and men from our laboratory cell panel. No significant deviation from the calculated control mating frequencies was observed in the group with habitual abortions. When the study and control couples were grouped by ethnic origin into Ashkenazim and non-Ashkenazim, the frequencies of shared HLA-A, -B, and -DR antigens were similar in both groups. These results do not confirm the observations of greater HLA compatibility between partners of aborting couples reported by other laboratories. Moreover, the results of an informative family in which the woman, after three consecutive spontaneous abortions, conceived and bore a healthy male infant genotypically HLA-identical to his mother are presented. Taken together, these results challenge the concept that compatibility in determinants of the major histocompatibility complex have a major role in habitual abortions.

Abortion, Habitual↗

Is predisposition to pemphigus vulgaris in Jewish patients mediated by HLA-Dw10 and DR4?

Twenty-one Israeli Jewish pemphigus vulgaris (PV) patients were studied for the HLA-D lymphocyte defined determinants and the serologically defined antigens of the HLA-A, B, and DR series. HLA-D typing revealed that Dw10 is significantly associated with PV: 86% of patients vs 18% of controls carried Dw10, and DR4 was present in 86% of patients as compared to 38% in the controls. The most striking observation was that all Dw10 positive patients were also positive for DR4, and no other patient carried DR4 alone. The relative risk for a Dw10-DR4 carrier to develop PV was estimated at 31.9, higher than that observed for Dw10 alone (RR 26.7) or DR4 alone (RR 9.6). Probably HLA-Dw10 predisposes for pemphigus vulgaris.

Epitopes↗

Enzyme-linked immunosorbent assay for determination of HLA: gene dose effect.

In a previous publication we demonstrated that polymorphic HLA antigens could be detected on fresh and dried peripheral blood lymphocytes using the enzyme-linked immunosorbent assay (ELISA) with HLA alloantisera (Bishara et al. 1983). In the present study we investigated whether the ELISA technique can be used in determination of gene-dose effect for antigens of the HLA-A and B loci. Lymphocytes from HLA-A1 and HLA-B14 homozygous individuals are shown to bind significantly more anti-HLA alloantibodies than their heterozygous siblings for the same HLA antigens. These results indicate that ELISA is a sensitive and reliable technique for the qualitative and quantitative assay of polymorphic HLA determinants.

Adult↗

HLA-D clusters associated with DR2 and the definition of HLA-D"AZH": a new DR2 related HLA-D specificity in Israel.

In order to investigate the HLA-D clusters associated with DR2 in Israeli Jews, 40 DR2 positive unrelated individuals were studied with a panel of DR2 associated homozygous typing cells (HTC's) which detect the lymphocyte defined specificities HLA-Dw2, Dw12, Dw9 and D-WJR. The results confirmed the existence of two distinct HLA-D clusters associated with the same serologically defined DR2. Of 40 individuals 22.5% (9/40) were Dw2 and 50% (20/40) were Dw12 carriers. Yet, no HLA-D specificity could be assigned to the remaining 11 DR2 positive individuals. In the present study we have defined a unique DR2-associated Dw specificity, HLA-D"AZH". The donor of the HTC was of Moroccan origin and an offspring of a first cousin marriage. This cell was not typeable with the known DR2-associated homozygous typing cells nor with other HTC's which define the well established HLA-Dw1 to Dw11 specificities. It was shown to segregate with DR2 positive HLA haplotypes in family analysis and in a population study, typed out 7 of 11 unrelated DR2 positive, Dw blank individuals, thus identifying a unique and new HLA-D cluster provisionally designated D"AZH".

Epitopes↗

HLA-linked SB antigens in Israel. Population study, analysis of homozygous typing cells and generation of local SB reagents.

In the present study we have investigated the HLA-SB antigen distribution in 65 unrelated Israeli Ashkenazim and non-Ashkenazim and in a panel of 18 local homozygous typing cells (HTC). Two locally derived SB reagents, anti-SB2 and SB3, were also studied. The HLA-SB allele frequencies in the Israeli sample ranged from 0.02 for SB1 to 0.47 for SB4 while SB5 was absent. SB3 had a higher frequency in non-Ashkenazim (0.11) as compared to Ashkenazim (0.06) but this difference was not significant. On the whole, the allele frequencies for the 5 HLA-SB antigens studied were in the range observed in non-Jewish Caucasoid populations with some minor variations. Two of eighteen local HTC's were found heterozygous for SB, demonstrating that homozygosity for HLA-A, B, C, D and DR does not indicate homozygosity for HLA-SB. The local anti-SB2 and SB3 typing reagents gave concordant results when compared with the NIH reference typing cells in population studies.

Europe↗

HLA-DR2 and DR4 further defined by two new HLA-D specificities (HTC) derived from Israeli Jewish donors: comparative study in Caucasian, Korean, Eskimo and Israeli populations.

Two newly-identified HLA-D antigens were characterized by testing selected homozygous typing cells (HTC) against responder panels derived from Caucasian, Korean, Alaskan Eskimo and Israeli Jewish populations. The first specificity, defined by typing cell "AZH", is associated with DR2 haplotypes and is detected primarily in Israelis. The second specificity, defined by HTC "TAS", is associated with DR4 haplotypes and is detected with relatively high frequency in Koreans and Alaskan Eskimos. The data indicate that HTC-AZH and -TAS can be used to identify previously undefined splits or variants of lymphocyte-defined (LD) determinants associated with DR2 and DR4 haplotypes. Further, the study demonstrates the utility of comparative population analysis in identifying and characterizing alleles encoded by the HLA-D region and provides additional evidence of heterogeneity within the family of serologically-defined HLA-DR haplotypes.

HLA-DR Antigens↗

Coeliac disease in the Rehovot-Ashdod region of Israel: incidence and ethnic distribution.

The data from a large group of children with biopsy proved coeliac disease born in the Rehovot-Ashdod region of Israel and treated in a regional hospital provided us with the basis for the determination of the annual birth cohort incidence of coeliac disease for the period 1968-81. The findings show a minimum birth cohort incidence of 1.71/1000 live births. The highest incidence rate was in children of Asian origin and the lowest in second generation Israel born. The incidence of coeliac disease rose sharply during the study period.

Celiac Disease↗

Ethnic differences in kidney graft survival.

Results of 73 first cadaveric donor renal transplants in Jerusalem between 1975 and 1980 are presented. There was a better 12-month graft survival in Arabs than in Jews (70.8% vs. 40.8%, P less than 0.035); however, 12-month patient survival was similar (83.3% vs. 85.7%). Acute rejection as the primary cause of graft loss occurred in 12.5% of the Arabs and 38.8% of the Jews (P less than 0.05). HLA-A, -B and -DR antigen-sharing was similar in both groups. Early acute rejection episodes had a poorer prognosis in Jews. Possible explanations for these findings are discussed, but the reason for the higher success rate in Arabs remains obscure.

Adolescent↗

T lymphocyte culture established by repeated stimulation with the autologous lymphoblastoid line. MHC class II restricted interactions with B blasts.

An OKT3+T4+T8-DR+ lymphocyte line was developed from an Epstein-Barr virus (EBV) seropositive individual by repeated stimulation in vitro with autologous EBV-infected B cells. The T cell population designated E-44 was carried for eight months in the presence of Interleukin-2 and was repeatedly tested for cytotoxicity, proliferation and lymphokine production in response to the autologous and a panel of allogenic B cells. The E-44 cells lysed the autologous lymphoblastoid cell lines (LCL) and allogenic B cell lines sharing the DR6.1 major histocompatibility complex antigen with the lymphocyte donors. The EBV genome-negative lymphoma line BJAB and its two, infected in vitro, EBV-positive sublines were lysed with similar efficiencies. Autologous Staphylococcus aureus protein A (Prot-A) induced B, but not Phytohaemagglutinin (PHA)-induced T blasts were also lysed. It is likely that E-44 recognized an antigenic component derived from the fetal calf serum in association with class II determinants expressed on the B cells. Preincubation of E-44 cells with saturating amounts of OKT3 and Leu3a monoclonal antibodies abrogated the lytic effect on the autologous LCL. Cold target competition experiments demonstrated that, within, the population, the same cells reacted with the autologous Prot-A-induced blasts, the EBV-transformed LCL, and also with Daudi (an EBV genome-positive BL line). Although Daudi was the target which was lysed with the greatest efficiency, the avidity of interaction was highest with the autologous LCL because these cells competed best. Among the cells that were sensitive for the lytic effect, only the autologous LCL and Prot-A-induced B blasts triggered release of detectable amounts of Interleukin-2 and induced proliferation of the culture. The results suggest that the affinity of interaction with the target may be decisive for the triggering of the various T cell functions.

Antigens, Differentiation, T-Lymphocyte↗

Unusual association of insulin-dependent diabetes mellitus with congenital myasthenia gravis and autoimmune thyroid disease.

A 26-year-old woman with congenital myasthenia gravis and antibodies to the acetylcholine receptor developed overt insulin-dependent diabetes with positive islet cell antibodies and thyroid microsomal and gastric parietal cell antibodies. Her younger sister has been an insulin-dependent diabetic since the age of 7 years, and the mother has nongoitrous hypothyroidism. In the same period the woman in question developed a transient chemical hyperthyroidism. HLA typing of the family members showed that the diabetes was probably associated with an HLA AW30, BW38, DR4 haplotype, found in both sisters and in their father, and that the thyroid disease was associated with the A29, B7, DR6 haplotype found in the patient and in her mother. This familial HLA pattern may indicate that each autoimmune manifestation in the patient is due to a different susceptible gene associated with the HLA system.

Adult↗