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PubMed1986

Immunogenetics of development and its relationship to carcinogenesis.

We have been exploring the classical idea that there is a close relationship between embryogenesis and carcinogenesis. The clinical literature provides evidence for a relationship among the presence of developmental anomalies, an increased incidence of cancer, and genes linked to the major histocompatibility complex (MHC). This relationship was explored experimentally by testing the possibility that rats having the growth and reproduction complex (grc), which causes developmental abnormalities, might be more susceptible to the development of cancer following exposure to a chemical carcinogen. Two groups of animals which were genetically similar except for the presence or absence of the grc were fed the carcinogen 2-aminoacetylfluorene. The animals carrying the grc developed the morphological changes associated with early cancer of the liver, whereas their normal counterparts did not. These susceptible animals also had a number of biochemical alterations, especially in cholesterol biosynthesis, which may be associated with the development of cancer. Molecular analysis of genomic DNA by blot hybridization revealed restriction fragment length polymorphism differences between the DNA from grc and grc+ rats, and these differences may be related to the differential susceptibility of the strains to cancer.

Abortion, Habitual↗
PubMed1979

Immunogenetic bases of congenital malformations: association of HLA-B27 with spina bifida.

A random sample of 46 families with single and multiple cases of spina bifida has been selected from families referred to the Institute of Pediatrics for genetic counseling. This sample constituted a group of 92 patients and 102 offspring: 41 normal, 46 with spina bifida, and 13 with spina bifida occulta. Routine HLA typing was performed on the parents and their children. For each case, 13 HLA specifities from locus A and 15 from locus B were determined. Segregation analysis in families showed excellent agreement with the expected values. HLA gene frequencies in the affected children as compared with a control population of 240 normal adults, revealed significantly higher frequency for HLA-B27 allele: chi 2 = 11.9515, P (corrected for the number of alleles) less than 0.028. A significant relative risk of spina bifida development for a given HLA-B27 antigen was 2.7. In view of the presented results, routine HLA typing might be recommended for genetic counseling as a new tool for identification of high risk families.

Chromosome Mapping↗
PubMed1984

Developmental and immunogenetic features of biologic aging.

As the direct result of improved health measures and medical/dental care during the 20th century, the longevity of individuals within the United States has significantly lengthened from 45 years in 1900 to 75 years in the 1980s. It is now projected that during the remaining 2 decades of the 20th century, approximately 18% of the total American population will be 65 years and older by the year 2000. Paradoxically, success in reducing acute diseases and postponing death has resulted in costly long-term disabilities and complexities of chronic disease. This review focuses, therefore, on the major issues of prevention of chronic diseases to demonstrate that biologic aging is a normal sequela of developmental biology and not a disease; diseases are separated from aging. Emphasis is placed on advances in genetics, molecular biology, immunology, and neurology toward understanding the ultimate prevention of chronic disease. An emphasis on prevention during the development of the individual, from conception through senescence, is necessary.

Adolescent↗
PubMed2006

Immunogenetics and infectious diseases: special reference to the mayor histocompatibility complex.

Many studies have tried to identify genetic markers for infectious diseases, some of them have focused on human leukocyte antigens (HLA). The products of HLA genes interact with surface-specific receptors of T lymphocytes, resulting in activation of the host's immune response. Association of bacterial, viral, parasitic and fungal infections with the host's HLA has been widely investigated. The type and strength of this association differs among distinct populations, as well as among racial and/or ethnic groups. The new molecular methods for the identification of the HLA alleles, and the resulting new nomenclature, have contributed to a better understanding of this system. Unfortunately, this information has not been adequately transmitted to clinicians, which hampers the understanding of the association between the HLA system and diseases. We revised relevant studies on the association of HLA genes with infectious diseases, demonstrating their importance in the pathogenic mechanisms, through increased susceptibility or protection against infections and their complications.

Alleles↗
PubMed1995

Immunogenetic determinants and prediction of IDDM in French schoolchildren.

Islet cell antibodies (ICAs) are predictive markers of the disease in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM). The large majority of newly diagnosed cases, however, will develop in children with no family history of diabetes. In France, the risk for development of IDDM up to the age of 20 years is 60 times higher in first-degree relatives than in the general population. The aim of this study was to test whether data collected in the first-degree relatives of IDDM patients could be transferred to children for the prediction of overt diabetes. A large population-based cohort of French school-aged children (n = 13,380; ages 6-17 years) were screened for ICAs, and results were compared with those of 1,185 first-degree relatives of IDDM patients. ICA prevalence rates were significantly different in the two populations (5.5% vs. 1.5%; P < 0.0001), with a significantly higher proportion of high ICA titers in first-degree relatives (37%) than in schoolchildren (14%) (P = 0.0005). ICA titers remained remarkably stable in children over 4 years. Insulin autoantibodies (IAAs) were found in 3.4 and 15.4% of ICA+ children and first-degree relatives, respectively. Susceptibility alleles at the human leukocyte antigen (HLA)-DQB1 locus were observed significantly more frequently in children in whom ICA titers > or = 20 Juvenile Diabetes Foundation units (JDF U) were found on two separate occasions (67%) than in ICA- children (52%) (P = 0.05). Five subjects developed overt diabetes during follow-up. ICA titers of > 20 JDF U were found in all of them on the first sample and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.

OBJECTIVE: When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS: This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS: The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups. CONCLUSIONS: Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Adult↗
PubMed1987

Immunogenetics of juvenile chronic arthritis.

The current knowledge of the relationship between the HLA system and the different forms of Juvenile Chronic Arthritis is reviewed: Of the different forms the Early Onset Pauciarticular JCA is associated with DRw8, DR5 and A2, the Polyarticular Onset Rheumatoid Factor positive JCA shows the same pattern of association as does the Adult Rheumatoid Arthritis namely with DR4 and DR1. Juvenile Spondylitis is strongly related to the presence of B27. For the other clinical forms of Juvenile Chronic arthritis the data are not sufficiently well established to give a definite association. In Early Onset Pauciarticular JCA the association with the DR antigens DRw8 and DR5 is independent of that with HLA-A2. Thus there must be at least two HLA linked regions contributing to susceptibility to this form of JCA, one in the region of HLA-A and the other one in the HLA-DR region. If Early Onset Pauciarticular JCA is analysed according to the type of onset (Monoarticular, with large joints, with large and small joints, with small joints only and with Iridocyclitis) there are no significant differences in the frequencies for the associated DR alleles DR5 and DRw8. The antigen DR4 is not found at all in patients with Monoarticular Onset and in increasing frequencies with the increased number of involved joints. Analysis of the same patients according to the clinical course of the disease (Persistent Pauciarticular, Extended Pauciarticular, Polyarticular) shows that again there are no significant deviations for the associated antigens A2, DR5, DRw8. DR4 is not found in the group with Persistent Pauciarticular Disease.

Adolescent↗
PubMed1991

Rheumatoid arthritis in identical twins: a clinical and immunogenetic study of eight concordant pairs derived from a nationwide twin panel.

The nationwide Finnish Twin Cohort was linked with the national Sickness Insurance Register. Eight identical twin pairs concordant for rheumatoid arthritis (RA) fulfilling the American Rheumatism Association criteria were identified. All 16 cases were known to be seropositive. Four pairs had at least one additional first-degree relative with RA, and the prevalence of RA among all the first-class relatives was 9%. HLA-typing was performed for 15 patients representing the eight pairs; six pairs carried the DR4 allele, and three of these pairs were putative homozygotes. Nodules and Sjögren syndrome occurred fairly frequently (in 7 of 16 and 6 of 13 cases examined, respectively), but concordance within pairs was no higher than that expected by chance. The course of the disease was fulminant in one patient and in several others the disease had led to marked joint destructions. The findings pointed out to some intrapair similarity in the progression of the joint damage and in the type of complications caused by gold.

Adult↗
PubMed1991

Immunogenetics in Chinese patients with SLE.

100 consecutive Chinese patients with SLE were recruited for study of HLA-A, B and DR antigen. Clinical and serological parameters were analysed with respect to the HLA antigens. B5 was associated with presence of other autoimmune diseases (thyrotoxicosis, myasthenia gravis, diabetes mellitus, corrected p less than 0.025); absence of malar rash (corrected p less than 0.025); B35, with male sex (corrected p less than 0.025); DR2 with anti-Ro (anti-SSA) antibody (p less than 0.05). Previous study of association with B13, B17 was not present in our cohort. Except for malar rash, subclassification of disease status with respect to HLA antigen did not reveal significant association.

Adult↗