SUMMARY Forty-nine Israeli Jewish patients with rheumatoid arthritis (RA) were studied for their HLA A, B, C, DR antigen frequency. A significant increase in HLA Aw3l and HLA DR1 was observed (p<5 100' and p<5 10 ' respectively). 45% of Aw31 positive patients were seronegative for rheumatoid factor, while most HLA DR1 positive individuals were seropositive. DR5 was found to be significantly decreased (p<5 10-4). Contrary to previous reports, DRw4 was found to be within the range of antigen frequency of the controls (34*7 % vs. 32 %). It is suggested that in our population of patients Aw3l and DR1 and not DR4 are highly associated with adult onset of RA.Rheumatoid arthritis (RA) is a diseases with abundant evidence for immunological abnormalities, and it was therefore of interest to look for its associations with the major histocompatibility complex.' In the past, testing for the HLA A and B polymorphisms did not yield any significant associations with RA,' but, when HLA D and DR were described and tested for, it was readily established that adult onset of RA is significantly associated with HLA Dw4 and DR4.3-6 These observations were later confirmed by several investigators working collaboratively during the 7th and 8th International Histocompatibility Workshops.7 8 In familial RA it was later possible to map the susceptibility locus RLA-1 to chromosome 6, centromeric to locus HLA D.9We have observed in the past that our population does not always follow the same HLA and disease association,'01' and it seemed important to reevaluate the situation in our RA patients. Table. HLA Aw3l and DR1 were both increased. Aw3l frequency was 18 4 % in the total patient group compared with less than 1 % in the control population (p<5 10-'). Similar results were obtained when the 403 on 11 May 2018 by guest. Protected by copyright.
The aim of this study was to evaluate the screening policies of cystic fibrosis (CF) in the Jewish population. The prevalence of mutations that account for CF in Israel have been defined in the past by determining the frequency of CF mutations in affected individuals. This study is a population-based study and is, therefore, different from previous patient-based studies. We found that the CF mutations D1152H, W1089X, and 405 + IG-->A were present in some ethnic groups in which no CF patients carrying these mutations were reported. These facts necessitate a reevaluation of the screening policy regarding the ethnic groups in Israel. We studied 9,430 healthy Jewish Israeli individuals of 36 countries of origin. The prevalence of CF mutations was 1:19, 1:19, 1:28, and 1:42 for the Ashkenazi, Sephardi, North African, and Eastern Jews, respectively. CF mutations were identified in 374 (4.0%) individuals. These included 173 (46.3%) carriers of the W1282X mutation; 110 (29.4%) found to carry delF508; 23 (6.1%) who carried G542X; 22 (5.9%) who carried 3849 + 10Kb (C-->T; 20 (5.3%) who carried D1152H; 10 (2.7%) who carried N1303K; 11 (2.9%) who carried 405 + IG-->A; 4 (1.1%) who carried W1089X; and one (0.3%) who carried S549R. No carriers were detected for the 1717-1G-->A, G85E, and T360K mutations, which were tested for in 7,383, 1,558, and 41 individuals, respectively.
Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P = 0.01) and from 44.4 to 67.5% (P = 0.001) in primary aborters with >/= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.
Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3–12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.
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