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Biomedical subjects

A Amar

Publications and source records attributed to A Amar.

At least 73 records · Page 4Linked to original sources

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↗

Specific allelic variation among linked HLA class II genes.

Locus-specific oligonucleotides have been used as probes to detect polymorphic alleles for the HLA genes DQ beta, DQ alpha, DX alpha, and DO beta. These genes lie between the HLA DR and DP genes on chromosome 6, a region frequently implicated in intra-HLA recombination. In order to distinguish among these highly homologous HLA class II genes, we have identified sequences in the coding regions that are locus specific and have synthesized short oligonucleotide probes corresponding to these regions. We have used these probes in a gel hybridization procedure to analyze restriction-enzyme-digested genomic DNA and to assign polymorphic bands to a particular locus. Taq I-digested DNA hybridized with a DQ-beta-specific probe detects a single band per haplotype. The size of this band corresponds precisely to the expressed DQ beta gene and distinguishes among the serologically defined DQ alleles, providing a rapid method for genomic DQ typing. Similar analysis with an oligonucleotide probe specific for DX alpha, the nonexpressed alpha gene in the DQ subregion, detects 2 DX alleles, and hybridization with an oligonucleotide specific for the newly described DO beta gene detects 2 alleles at DO beta. Heterogeneity in linkage patterns among DQ, DX, and DO genes suggests that frequent recombinational events at multiple intergenic sites contributed to the generation of present-day haplotypes. One such recombinational event was identified directly in a family with serologically HLA-identical siblings, in which genomic analysis indicated a parental recombination event mapping between DR and DX, which correlated with unexpected alloreactivity.

Alleles↗

Polymorphism of the HLA DR1 haplotype in the Israeli population investigated at the serological, cellular, and genomic levels.

In the present report, we used serological, cellular, and restriction fragment length polymorphism (RFLP) to investigate the DR1 haplotype in the Israeli population. We describe an Israeli homozygous typing cell (HTC), HLA-Dw"LVA", which defines a new lymphocyte-activating determinant associated with Bw65, DR1 and distinct from Dw1. The parents of this donor, non-Ashkenazi Algerian Jews, are first cousins and share HLA-Cw8,Bw65,BfS,DR1,DQw1,DPw4. No specificity could be assigned to HLA-Dw"LVA" using the 91 Ninth Workshop HTCs. Two families and forty unrelated DR1 individuals were studied with Dw"LVA" and a panel of DR1/Dw1 HTCs. HLA-Dw"LVA" showed segregation as a single determinant within families. This new specificity was present in 24 out of 40 (60%) unrelated DR1 individuals, indicating that in the Israeli population Dw"LVA" is the main lymphocyte-defined determinant associated with the serologically defined DR1 specificity, in contrast to non-Jewish Caucasoids where DR1 is significantly associated with Dw1. The vast majority of Dw"LVA"-positive carriers were also Bw65 carriers, indicating that Bw65,DR1, Dw"LVA" may represent a typical allele combination in the Israeli population. The RFLP analysis established the correlation of certain RFLPs with Dw1 and Dw"LVA". In addition, we describe a cluster of FRLPs that may correspond to a new Dw subtype associated with DR1, for which no serological and cellular reagents have been described so far.

DNA Restriction Enzymes↗

Immunogenetics of rheumatoid arthritis in Israel.

In an attempt to study the variation of associations between HLA and rheumatoid disease a population of 44 Ashkenazi and 29 non-Ashkenazi patients with Rheumatoid Arthritis were tested for HLA-A, B, C and DR antigens and compared with the relevant control groups. In contrast to the results obtained in Middle European or North American Caucasians, Rheumatoid Arthritis in Israel is not associated with B15 and Cw3, indicating that it is very unlikely that B- and C-locus antigens are involved in coding for disease susceptibility for RA. The allele DR4 which is found associated with RA in almost all populations tested so far was in the total patient group (47.9%) slightly but not significantly more frequent than in the control group (38.3%). This difference was entirely due to a nonsignificant increase in the frequency of DR4 in the Ashkenazi patients (54.5%) compared to controls (40%), while the frequency of DR4 in non-Ashkenazi patients and controls was virtually identical (38.0% vs 36.7%). Another surprising finding was that the frequency of HLA-DR1, which has been reported to be increased in different populations of patients with RA was found to be completely normal in the present study on Israeli patients. The alleles of the Bf and the GLO system did not show any significant difference between patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗

HLA-DQ heterogeneity among HLA-DRw11(5) haplotypes.

Class II molecular variation among a panel of ten HLA-DRw11(5) homozygous cell lines (HCL) was investigated by analysis of restriction fragment length polymorphisms in genomic DNA. Hybridization of Bgl II, Hind III, and Taq I digested cellular DNA with DQ alpha and DQ beta cDNA probes identified a clustering of characteristic polymorphisms. Considerable diversity was observed between the HLA-DRw11(5), DQw3 positive haplotypes studied, as well as compared to a DRw11(5), DQw1 positive haplotype. In contrast to the observed DQ genomic variability, hybridization with a DR beta probe revealed relatively limited diversity. The molecular heterogeneity seen by genomic restriction fragment analysis illustrates the presence of genomic polymorphisms, particularly within HLA-DQ-related genes among a family of DRw11(5)-related haplotypes.

B-Lymphocytes↗

Immunogenetics of juvenile chronic arthritis in Israel.

Typing for HLA-A,B,C and DR antigens was performed in 61 Israeli patients with juvenile chronic arthritis (JCA) and in 120 unrelated controls. No significant associations were apparent in the overall patient group. DR5 was significantly increased in the non-Ashkenazi patients with pauciarticular onset of disease. The only three DRw8 positive patients in the study had pauciarticular onset. DR5 and DRw8 were found in 9 of 10 patients with age of onset less than 3 years. Increased frequencies of Bw50 and Cw6 were observed in patients with systemic onset. Typing for properdin factor (Bf) and glyoxylase (GLO) was carried out in 45 and 50 of the patients, respectively. No associations with alleles of the complement Bf system or the HLA linked GLO system were evident. The confirmation in the ethnically distinct Israeli population of the previously described association of DR5 with pauciarticular JCA suggests that this gene may be closely related to the disease susceptibility gene.

Adolescent↗

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↗

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↗

[Surgical treatment of Basedow's disease. II--Evaluation of 36 subtotal thyroidectomies].

Results of subtotal thyroidectomy in 36 patients with Graves' disease emphasize the need for strict medical preparation, with the administration of corticoids more particularly, and the technical imperatives required during operation. Analysis of endocrine factors showed that euthyroidism was obtained in 76% of cases with a fairly stable state after 6 months. Hyperthyroidism was rare and developed before the end of the first year. Hypothyroidism, mainly biologic, was frequent during the immediate postoperative period but compensatory hypertrophy of remaining tissue was the usual outcome. It was persistent in 14% of cases, however, but easily compensated by substitutive therapy and a less severe complication than prolonged hyperthyroidism. Biologic hypocalcemia was also frequent but normal levels were reinstituted rapidly. Surgical treatment of Graves' disease is usually effective and rapidly performed, and is particularly indicated when socio-ethnic conditions make medical treatment difficult or impossible.

Adolescent↗

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↗