Organ-specific autoantibodies in HLA genotyped insulin-dependent diabetes mellitus families.

The prevalence of cytoplasmic islet cell antibodies (ICA) and extrapancreatic antibodies (EPA), (stomach, adrenal and thyroid) was investigated in 132 juvenile onset diabetic patients, without personal or familial history of other autoimmune disease, and their 31 diabetic and 402 non-diabetic first degree relatives. The prevalence of ICA was 59% in index cases and 12% in the non-affected first degree relatives. The frequency of EPA was 23% and 16% respectively. There were no sex-related differences among the patients. However, among the non-affected relatives, an increased frequency of EPA was observed in females (23%) compared to males (8%) (P less than 10-4). There was a higher prevalence of ICA in healthy relatives bearing DR3 and/or DR4 antigen combinations compared to non-DR3 and non-DR4 individuals (14% versus 5%, P less than 0.05). Furthermore, ICA were more frequent in healthy siblings sharing two haplotypes compared with one or no haplotype (21% vs 10%, P less than 0.05). These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background.

[4 varieties of islet cell antibodies in 74 insulin-dependent diabetics and their families as a function of the HLA genotype]. / Etude de 4 variétés d'anticorps anti-îlots de Langerhans chez 74 diabétiques insulino-dépendants et leur famille en fonction du génotype HLA.

The sera of 74 diabetic patients and of their first degree relatives were studied for 4 different types of islet cell antibodies (ICA, CFICA, ICSA, ICACT) and the results were compared according to the HLA genotype. Seventy two percent of the patients' sera were positive for at least one type of auto-antibody. Two types of auto-antibodies were observed: anticytoplasmic antibodies (ICA and CFICA), and surface antibodies (ICSA and ICACT). The different types of antibodies were not associated with any HLA-DR. These antibodies were also present in 15% of the healthy relatives. The fact that they were detected in the sera of siblings sharing no haplotype with the proband, some of them bearing neither DR3 nor DR4 antigens, suggests that non HLA linked genes and/or environmental factors partly control their secretion.

Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-A, -B and -C specificities in insulin dependent diabetes mellitus in the Egyptian population.

The diversity of HLA antigens frequencies associated with Insulin Dependent Diabetes Mellitus (IDDM) reported in different populations raised the importance of determining HLA-A, -B and -C specificities in patients with IDDM in the Egyptian population. The study has been carried out on thirty patients with IDDM and thirty healthy control subjects matched for age and sex as patients included in the study. The results of the present work showed that patients with IDDM showed a significant increase in frequency of HLA-A2, HLA-B8 and HLA-B15. These findings are in accordance with the genetic heterogeneity of IDDM which is in turn in harmony with the modern concept on the complex aetiology of the disease. On the other hand, HLA-A3, HLA-B5 and HLA-B7 have been found significantly decreased in patients with IDDM, thus suggesting that these alleles may confer a protective effect from acquiring the disease. When HLA specificities have been studied in relation to the age of onset of the disease, HLA-A29 have been found in higher frequency in the age group after 15 years, while HLA-B15 in that before 15 years. This variability may be related to variation in the viral agents responsible for the infectious mechanism.

The role of porto-systemic shunts in the specific humoral immune response in patients with schistosomal hepatic fibrosis.

The present study was devoted to elucidate the role of collaterals (porto-systemic shunts) in the specific humoral immune response to schistosomal soluble egg antigen (SEA) in patients with schistosomal hepatic fibrosis (SHF). Twenty five patients with SHF with collaterals, ten patients with SHF without collaterals and twenty healthy control subjects constituted the material of this study. In vivo and in vitro tests for humoral immunity to SEA included serum immunoglobulins estimation, immediate intradermal test, indirect haemagglutination test and determination of B lymphocytes count in peripheral blood. Significant differences have been observed between cases without collaterals and those with collaterals; and in the latter group before and after decongestion. These results tend to consolidate the view of the role of collaterals in schistosomal antigenemia and subsequent humoral immune response.

[Value of genetic studies and immunologic markers in diabetes. Prediction of insulin dependence]. / Intérêt des études génétiques et des marqueurs immunologiques dans le diabète. Prédiction de l'insulinodépendance.

A new classification based on physiopathological criteria distinguishes Type I diabetes, observed in patients with stigmata of anti-islet of Langerhans auto-immunity, from Type II diabetes without these autoimmune changes. Type I diabetes is sub-divided into Classes Ia and Ib, Class Ib comprising those cases associated with other auto-immune diseases. Serological analysis of 76 patients with clinical type Ia diabetes and 215 healthy, first degree relatives showed that the distinction between Classes Ia and Ib was not clear-cut and that patients classified clinically Ia were in fact infraclinical Ib subjects. Forty-one per cent of patients with Class Ia diabetes had anti-gastric, anti-adrenal or anti-thyroid antibodies, and 28 p. 100 of their healthy relatives also had the same types of antibodies. Several prospective studies of the families of patients with Type I diabetes have shown that anti-islet of Langerhans antibodies were associated with a high risk of diabetes. Similarly, the presence of these antibodies in patients apparently with Type II diabetes (non-insulin dependent) was associated with an increased risk of developing insulin dependence. These results illustrate the value of immunological investigations in diabetic patients. They may influence the choice of treatment in the future.

HLA-A, -B and -C specificities in a sample of the Nile Delta population, Egypt.

HLA-A, -B and -C specificities were determined in 100 Egyptians living and originating from the region of the Nile Delta. The pattern of antigen frequencies were similar to those of Berber populations living in North Africa with some exceptions compatible with the Semitic contribution to the Egyptian population.

Cell mediated immune (CMI) responsiveness to soluble egg antigen (SEA) and its relation to the occurrence of schistosomal hepatosplenic disease in patients with schistosomiasis mansoni.

The delayed intradermal test and migration inhibition tests were used to assess the delayed hypersensitivity in patients with BHF and simple intestinal bilharziasis using SEA. All bilharzial patients gave a positive intradermal test. The specificity of the intradermal test using SEA is demonstrated clearly by the negative response in all control groups.