ABSTRACT
The aim of the present work was to characterize the immune status of 385 individuals who participated in the 1986-90 clean-up work of the after effects of the Chernobyl nuclear power plant explosion. Fifty-nine Chernobyl clean-up workers developed the most common thyroid diseases; euthyroid nodular and diffuse goiter; 47 healthy blood donors were taken as controls. The levels of immunoglobulins (IgA, IgG and IgM), the numbers of peripheral blood leukocytes, lymphocytes, monocytes, T lymphocytes and their subpopulations (CD3+, CD4+, CD8+), B lymphocytes (CD19+), natural killer (NK) cells (CD16+), classical and alternative pathway activity of complement (CH50, APH50), the C3 split product C3d, and neutrophil phagocytosis were determined in the peripheral blood. We found a significantly decreased number of CD16+ cells (natural killer), of CD4+ and CD8+ T lymphocytes, a reduced neutrophil phagocytic activity as well as a significant complement activation in Chernobyl clean-up workers with and without thyroid diseases when compared with normal levels and those in the control group. In addition, the number of CD3+ and CD4+ cells was significantly higher in patients with nodular goiter when compared with that in patients with diffuse goiter. Levels of IgG and numbers of monocytes were significantly decreased in persons who worked in Chernobyl in 1986 during the first 2 months after the accident (with maximal radiation exposure) but were without correlation to thyroid disorders. Our results clearly reflect an impaired immune system in the Chernobyl clean-up workers even 10-14 years after the nuclear accident.
Subject(s)
Occupational Diseases/etiology , Occupational Diseases/immunology , Radiation Injuries/etiology , Radiation Injuries/immunology , Radioactive Hazard Release , Thyroid Diseases/etiology , Thyroid Diseases/immunology , Adult , Case-Control Studies , Complement System Proteins/metabolism , Goiter/etiology , Goiter/immunology , Goiter, Nodular/etiology , Goiter, Nodular/immunology , Humans , Immunoglobulins/blood , Latvia/ethnology , Leukocyte Count , Male , Middle Aged , Phagocytosis , UkraineABSTRACT
The genes encoding the HLA-DQ heterodimer molecules, DQB1 and DQA1, have been found to have the strongest association with IDDM risk, although there is cumulative evidence for the effect of other gene loci within the major histocompatibility complex gene region. After the HLA-DQ locus, the HLA-DR locus has been suggested most often as contributing to the disease susceptibility. In this study we analyzed at the population level the effect of DR4 subtypes and class I, HLA-B alleles, on IDDM risk when the influence of the DQ locus was stratified. In all three populations studied (Estonian, Latvian, and Russian), DQB1*0302 haplotypes most frequently carried DRB1*0401 or DRB1*0404. DRB1*0401 was the most prevalent subtype in IDDM patients, whereas DRB1*0404 was decreased in frequency. DRB1*0402 was also prevalent among Russian haplotypes, but was not associated with IDDM risk. When HLA-B alleles were analyzed, strong associations between the presence of specific B alleles and DRB1*04 subtypes were detected. The HLA-B39 allele was found significantly more often in DRB1*0404-DQB1*0302-positive patients than in healthy control subjects positive for this haplotype: 27 of 54 (50%) vs. 4 of 49 (8.2%) (P < 0.0001). The results demonstrate that DQ and DR genes cannot explain all of the HLA-linked susceptibility to IDDM, and that the existence of a susceptibility locus telomeric to DR is probable.
Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/immunology , HLA-B Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Alleles , Diabetes Mellitus, Type 1/genetics , Dimerization , Estonia , Ethnicity/genetics , Gene Frequency , Genetic Markers , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Latvia , Reference Values , Risk Factors , RussiaABSTRACT
The rare HLA-DQB1*0304 allele was found increased among IDDM patients in the populations of the eastern Baltic region. Its frequency among IDDM patients was 4.5% (20/443) compared to 1.1% (9/853) in healthy controls in the combined series of Estonian, Latvian and St. Petersburg Russian populations (P=0.0001). HLA-DQB1*0304 in these populations was associated with DRB1*0408, and the haplotype was further characterized by a B35 allele and a typical combination of microsatellite markers from the TNF gene region. The result is compatible with the significance of the 57th amino acid in the DQ beta-chain but also emphasizes the importance of alleles in other HLA loci adjacent to DQ in the determination of IDDM susceptibility.
