Search PubMed⌕ Search

Biomedical subjects

C Brautbar

Publications and source records attributed to C Brautbar.

At least 181 records · Page 10Linked to original sources

Enzyme-linked immunosorbent assay for HLA determination on fresh and dried lymphocytes.

HLA-A and -B antigens were detected on fresh and dried peripheral blood lymphocytes by an enzyme-linked immunosorbent assay. Intact cells fixed to plates with glutaraldehyde were used as antigen and anti-HLA alloantisera as a source of antibodies. Determination of HLA antigens by the ELISA technique was comparable with the complement-dependent cytotoxicity test. The relative stability of HLA antigens as shown in this report and the extensive polymorphism of the HLA system make the ELISA technique a promising tool for the analysis of HLA antigens on non-living cells including, for example, medicolegal investigation of blood stains.

Dose-Response Relationship, Immunologic↗

Genetically regulated human (T,G)-A-L specific helper T cell replacing factors possess HLA-DR and VH determinants.

Human (T,G)-A-L specific T cell helper factors secreted by in vitro activated peripheral blood lymphocytes of normal donors were characterized. Factors were passed through columns of Sepharose coupled either to antibodies against human immunoglobulin or antibodies against the variable region of the heavy (VH) and light (VL) chains of human immunoglobulin. In addition, the same factors were applied to columns of Sepharose coupled to anti-HLA-DR antibodies or to monoclonal antibodies against human Ia or beta 2-microglobulin. The activity of the antigen specific factors was removed by the anti-VH antibodies and not by anti-VL or anti-human immunoglobulin antibodies. The factors passed through Sepharose coupled to anti-DR antibodies could be removed and eluted from columns of anti-DR antibodies relevant to the donors' DR antigens. The same factors were also removed by a monoclonal antibody (anti-Ia) which recognizes a monomorphic determinant on HLA-DR, but not by monoclonal anti-beta 2-microglobulin. The results suggest that the genetically regulated (T,G)-A-L specific helper factors possess HLA-DR as well as VH determinants in their active moiety.

Animals↗

Familial gonadal germinative failure: endocrine and human leukocyte antigen studies.

Two primary amenorrheic sisters were diagnosed as 46,XX pure gonadal dysgenesis. Their brother, a normal phenotypic and genotypic male, was azoospermic due to primary germinative failure. Parental consanguinity was observed, suggesting an autosomal recessive inheritance. This is the first reported family in which both an otherwise healthy male and two females were affected by gonadal germinative failure. Endocrine studies showed impaired gonadal function in the three affected siblings. The two females with gonadal dysgenesis and the azoospermic male shared one human leukocyte antigen haplotype; the second haplotype, however, was different. The common haplotype was also found in the oligomenorrheic sister whose gonadotropin-releasing hormone test was compatible with normal ovarian function, in the mother, and in one of her offspring who had a normal spermiogram. Hence, linkage between human leukocyte antigens and gonadal failure in this family had been excluded. The possible etiology of familial, chromosomally competent, gonadal failure is discussed.

Amenorrhea↗

Suppression of mixed lymphocyte reactivity by cellular and humoral factors in aplastic anemia--both before and after bone marrow transplantation.

A patient with infectious hepatitis who developed severe aplastic anemia received a bone marrow transplant from her HLA-identical, mixed lymphocyte culture (MLC)-negative sister. It was found that pretreatment of normal lymphocytes with the immunoglobulin fraction of the patient's serum resulted in marked inhibition of their proliferative response to mitogens, as well as their ability to serve as stimulators and responders in MLC. The patient's lymphocytes, unlike those of her HLA-identical sister were unable to stimulate and respond in MLC and markedly suppressed mixed lymphocyte reactivity between two unrelated healthy individuals. Donor-type lymphocytes obtained from the patient after engraftment were also unable to respond or stimulate in MLC. It is suggested that the suppression of lymphocyte responses was mediated by an immunoglobulin present in the patient's serum.

Adult↗

Histocompatibility antigens, mixed lymphocyte reactivity and severe preeclampsia in Israel.

In the present study we have attempted to ascertain the possible existence of an association between antigens of the major histocompatibility complex (MHC) and development of severe preeclampsia (PE). HLA-A, B, C, DR antigens as well as reactivity in one-way mixed lymphocyte culture (MLC) were studied in 40 couples with severe PE, and subsequently compared to 30 normal fertile control couples. No significant differences in the frequencies of HLA antigens were detected between PE and control couples. The frequency of shared HLA-A, B and DR antigens among members of the couples was similar in both groups. The one-way MLC showed normal reactivity of both parental pairs in all combinations tested. Consequent to our data we are unable to support the suggestion that the MHC affects the susceptibility to develop severe PE.

Female↗

Mixed lymphocyte reactivity nonresponsiveness in couples with multiple spontaneous abortions.

We have endeavored to ascertain the possible existence of deviant recognition of antigens controlled by the major histocompatibility complex by lymphocytes originating in couples with a history of multiple spontaneous abortions of unknown cause. Human leukocyte antigen (HLA) typing, as well as one-way mixed lymphocyte culture (MLC) tests, were performed on 33 couples with multiple spontaneous abortions and subsequently compared to 30 fertile couples with no abortion history. No significant differences in the frequency of HLA were detected between the fertile and infertile groups. The frequencies of shared HLA-A and -B antigens among members of the couples were similar in both groups. In 70% of the cases studied, the husbands revealed a depressed cellular response to their respective wives; whereas reactivity to cells from other women proved normal. However, the response of allogeneic controls to these infertile women was normal. This implies that women with multiple abortions are not poor stimulators. The specific one-way decrease in the MLC reactivity appeared to be mediated by female-derived suppressor mechanisms and may be considered as one of the causes of the interrupted development of pregnancy in vivo.

Abortion, Habitual↗

HLA-D "BG" in Israel. A Japanese related allele population and family study.

An homozygous typing cell for a local HLA-D determinant"BG", defined by family study, is described. HLA-D "BG" recognizes a specificity identical to the Japanese HLA-DHO (Dw12). Two families and 102 randomly selected healthy Israeli individuals were typed for the HLA-D "BG" determinant. HLA-D "BG" showed segregation as a single determinant within families. The gene frequency for this allele was 0.045, compared to the frequency of 0.148 for DHO in Japanese. In the Israeli population "BG" is in strong association with HLA-Bw52 (joint occurrence = 7.80%) and DR2 (joint occurrence = 8.80%), resembling the data reported foar DHO (Dw12) in Japan. The frequency of this allele may partially account for the low frequency of HLA-Dw2 in the Israeli population.

Alleles↗

Study of a family with Cerebrotendinous Xanthomatosis. No HLA linkage, but an informative recombination between HLA-B and Bf.

A large family with three children affected with the autosomal recessive disease of Cerebrotendinous Xanthomatosis (CTX) was studied for class I (HLA-A,B,C) and class II antigens (HLA-DR,D,SB), properdin factor B and glyoxalase. The extensive typing revealed an informative cross-over between HLA-B and Bf, indicating that Bf is located centromeric to the HLA-B locus and segregated in this family with HLA-D/DR. The parents in this family were first cousins and their parents were also first cousins. Three of their four haplotypes share B14, BfS, DR1, Dx and SB4 and may be identical by descent. The three affected children carried among them all four parental haplotypes, indicating that close linkage of the CTX locus to HLA is unlikely.

Adolescent↗

HLA-DR, D recombination in a kidney transplant recipient.

Immunogenetic studies of a consanguineous family revealed discordance in the inheritance pattern of the HLA-D and HLA-DR antigens in one offspring. The findings suggest a recombination between the HLA-D and HLA-DR loci in one of the paternal chromosomes. Results on segregation of B-cell alloantigens. MLC reactivity, and glyoxalase isoenzyme determination map the DR gene between the HLA-B and D loci.

Chromosome Mapping↗

HLA-D locus in Israel. Characterization of 14 local HTC's and a population study.

Fourteen homozygous typing cells identified in Israel are described. Of these typing cells two were of Ashkenazi and 11 of non-Ashkenazi origin, while the remaining HTC was from an Arab donor. Ten of the 14 HTC's characterized in this manner were offspring of consanguineous marriages; all of them were non-Ashkenari. Nine HTC's express specificities previously recognized in Caucasians, 4 HTC's represent new specificities (J1-J4), and one typing cell was found to be analogous to the Japanese Dw12 (DHO) specificity. The distribution of HLA-D specificities in 120 randomly selected Israelis representing the two main Jewish subpopulations, Ashkenazim and non-Ashkenazim, was studied with the locally defined HTC's. HLA-Dw5 and Dw10 were found to be significantly increased while Dw2 and Dw6 were significantly decreased in Israelis as compared to Caucasians.

Chromosome Mapping↗

HLA-D typing in multiple sclerosis: Israelis tested with European homozygous typing cells.

The association of A3, B7, Dw2 and DR2 histocompatibility (HLA) markers with multiple sclerosis (MS) is well established among Northern Europeans and Caucasoids in the United States. We showed previously that A3 and B7 were not increased among Israelis with MS, and in a preliminary study Dw2 as well. An association of A3 and B7 is also lacking in Italians, Jordanian and Japanese MS patients. In Black American MS patients, the B7 frequency is slightly increased but Dw2 is still significantly associated with MS. For the HLA-DR antigen series DR2 is shown to have a stronger association to MS than A3 and B7. Conceivably, this antigen could be associated with MS even in populations where an association with A3 or B7 is lacking. Therefore, a study of HLA-A, B, C, DR and D antigens was carried out in Israel. No significant excess or deficiency of HLA antigens was found in MS. Possible explanations for these results are as follows: (1) the relevant HLA-D alleles in the Jewish population were not detected by the homozygous typing cells (HTCs) used, since they were derived primarily from European sources; (2) in contrast to the Caucasoid populations the genetic factor predisposing for MS is not associated with HLA alleles in the Israeli population; (3) MS is an heterogeneous disease and in Israelis, an environmental factor is sufficient to cause the disease.

Europe↗

Histocompatibility (HLA) antigens and multiple sclerosis in Israelis.

The association of A3, B7 and Dw2 histocompatibility (HLA) markers with multiple sclerosis (MS) is well established among North Europeans and Whites in the United States, but is apparently not universal. We previously showed that the incidence of A3, B7 and Dw2 was not higher among Israelis with MS. An association of A3 and B7 was also lacking in Italian, Jordanian and Japanese groups with MS. Recently, the HLA-DR antigen DR2 was shown to have a stronger association with MS than do A3 and B7. Conceivably, DR2 could be associated with MS even in populations where an association with A3 or B7 is lacking. Therefore, a study of DR antigens was carried out in 45 carefully defined Israeli MS patients and in matched control subjects. No significant association between MS and DR antigens was found. We conclude that the association between HLA antigens and MS is specific only to certain populations or particular regions. The implications of this observation on the role played by HLA antigens in the etiopathogenesis of MS is discussed.

HLA Antigens↗

Histocompatibility antigens and cell-mediated immunity in carriers of hepatitis B virus; a study of a family.

The cause of the HBsAg carrier state is unknown, and environmental genetic and immunologic factors have been implicated. Herein, a family is described in which the carrier state was associated with the HLA-A28BW15 haplotype and with impaired cell mediated immunity. The relevance of the genetic marker in this family is uncertain. It could be associated with a genetic susceptibility to the virus or alternatively with inherited immunodeficiency. According to the first possibility the impaired immunity could be secondary to the persistent viral infection. According to the second one the acquisition of the carrier state could result from the inherited immune defect.

Carrier State↗

Genetics of insulin dependent diabetes mellitus in Israel: population and family study.

The association between insulin dependent diabetes mellitus (IDDM) and the HLA system was studied in two groups of Jewish patients: 50 Ashkenazim and 42 non-Ashkenazim. The pattern of association of HLA-A and B locus antigens was somewhat different from that observed in European Caucasian patients. HLA-B8 had a higher frequency; B15 and Cw3 were rare in the population studied and were less frequent in IDDM patients than in controls. On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. Although the association between IDDM and HLA-A and B locus antigens shows a marked variability in different populations, the association with HLA-DR3 and DR4 is constant feature. There was a typical excess of DR3/DR4 heterozygotes in both patient groups. This heterozygote type carries the highest relative risk, followed by DR4/DR4 homozygotes. These data can well be interpreted by a model of two different HLA-linked susceptibility genes, one associated with DR3 and the other one with DR4, that interact so that different genotypes are associated with different levels of penetrance. This model received further support from studies in 15 multiple case families where there is an excess of affected sib pairs sharing two DR antigens.

Adolescent↗

HLA in a selective aldosterone biosynthetic defect due to type 2 corticosterone methyl-oxidase deficiency.

HLA phenotypes were studied in nine Jewish families, originating from Iran, with 18 individuals affected with a selective aldosterone biosynthetic defect and 12 healthy siblings. This disorder is inherited through an autosomal recessive gene and parents were consanguineously related in eight out of nine sibships. Family analysis showed that 18 affected individuals carried 20 different haplotypes and only two patients were homozygous for a haplotype. Yet a peak lod score of 1.128 was obtained for the recombinant fraction of 0.05 and thus linkage to HLA cannot be ruled out.

Aldosterone↗

Histocompatibility determinants in Israeli Jewish patients with coeliac disease: population and family study.

The association between HLA and coeliac disease (CD) was studied in the Jewish population of Israel. A total of 112 patients were typed for HLA-A,B,C antigens, including 67 patients whose families were typed in order to deduce the genotypes. Forty-seven patients were typed for HLA-DR antigens. The HLA-A,B,C data show a pattern of association, which is similar to that found in European CD patients: HLA-B8 is increased, although to a lower degree; a suggestive, insignificant increase for Aw30, B13 and Cw6 and a decrease of Bw35 were noted. The DR antigens DR3 and DR7 are associated with CD in the Jewish population. An excess of DR3/DR7 heterozygotes was noted. The data from family and population studies support a model in which two different HLA-DR associated genes are interacting.

Celiac Disease↗