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Comparison of clinical and immunogenetic features in familial versus sporadic psoriatic arthritis.

OBJECTIVE: To compare patients with familial versus sporadic psoriatic arthritis (PsA) with respect to clinical, radiological and immunogenetic features. METHODS: All patients were identified from the University of Toronto Psoriatic Arthritis Clinic. Familial and sporadic PsA were distinguished based on the proband's self-reported history. The probands were compared at presentation to clinic with respect to: demographic information, age of onset of psoriasis and inflammatory arthritis, disease activity, disease damage, laboratory variables, functional class and HLA antigens. The two groups were compared using a univariate analysis. RESULTS: In total 407 patients were included. Thirty-six patients (8.8%) were eliminated as they reported a family history of arthritis in the absence of psoriasis. Of the remaining 371 patients, 150 patients reported a positive family of either PsA or psoriasis. 221 patients (54.2%) had no family history of psoriatic arthritis, psoriasis, or "arthritis". The familial group were younger at presentation to clinic (p = 0.003), had an earlier age of onset of psoriasis (p = 0.001) and inflammatory arthritis (p = 0.001) and were more likely to be receiving treatment (p = 0.001). The mean number of actively inflamed joints was higher in the sporadic group (p = 0.035), along with a higher frequency of rheumatoid factor positivity (p = 0.04). Only the age of onset variables and medication use retained significance after correction for multiple comparisons. CONCLUSIONS: In comparing probands with familial versus sporadic PsA, we noted a marked difference in the age of onset of psoriasis and inflammatory arthritis, along with other differences in several clinical variables. These differences may be helpful in identifying PsA patients with a stronger genetic predisposition.

Adult↗

[Epidemiological and immunogenetic analysis of tuberculosis and diabetes mellitus association].

The prevalence of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) among adults in two Moscow okrugs was studied. It was 0.218 and 1.678%, respectively, the latter form being encountered 7.7 times more frequently. Patients with pulmonary tuberculosis followed at tuberculosis control dispensaries (n = 69,012) were found to have diabetes mellitus in 236 cases (120 with IDDM and 116 with NIDDM). The prevalence of IDDM among the tuberculosis control dispensary patients was 1.7%, which was 8 times greater than that in the general population. That of NIDDM was 1.68%, which did not significantly differ from that in the population. Epidemiological analysis showed that there was a highly significant association of tuberculosis with diabetes mellitus in the population. The risk for IDDM was 3.6% in patients and exceeded that in the population while the risk for NIDDM in the population was the same as that in the population. Analyzing the distribution of immunogenetic HLA-1 and HLA-2 markers showed that patients with tuberculosis concurrent with IDDM were intermediate between a group of patients with isolated tuberculosis and isolated IDDM.

Adolescent↗

[Characteristics of some breeds of swine and populations of Georgian and Western Siberian wild boar by immunogenetic systems of blood serum proteins].

A bank of reagents for hog serum protein allotypes has been created. All of these allotypes passed international comparison tests in 1987-1988. The bank can be used for typing the animals for four generally accepted (Gp, LpB, Lpr, and IgGH) and several experimental systems. In this study, immunogenetic characteristics of some pig breeds (Large White, Lithuanian White, Swedish Landrace, Kakhetinskaya, and Svanetskaya) bred in Georgia are compared with those of western Siberian breeds (Large White, Kemerovskaya, and Northern Siberian), and some foreign breeds, as well as with European, Caucasian, and Siberian subspecies of the wild boar.

Animals↗

Immunogenetics of Sjögren's syndrome.

The etiology for SS remains unknown where multifactorial influences contribute to the pathogenesis of subsequent development of the disease. The genetic influence is also multifactorial and the data suggests a familial component indicative of autosomal-dominant genes as well as genetic contributions associated with class-I and class-II HLA alleles. Various auto-antibodies found with increased frequency in SS (anti-Ro and anti-La) were shown to be associated with HLA class-II alleles at the DQA1 and DQB1 loci that were also found to have in common specific amino acid residues (10). Ethnic groups have also been studied and show varying HLA associations with primary SS. Multiple ethnic groups, however, share a DQ allele supporting the idea that the majority of SS patients carry a common allele which may predispose to primary SS. In some cases, the HLA-DR antigen may be induced and cause to appear on epithelial cells where they present antigen to CD 4+ T-cells, which then go on to aid in the destruction of salivary gland epithelial cells specifically. The further elucidation of disease associations as well as possible immunogenetic pathogenic mechanisms may help to explain the causes for the development of various autoimmune diseases such as Sjögren's Syndrome. This may eventually result in the ability to immunomodulate these abnormal immune responses. In so doing, an approach to treatment by genetic engineering may also be possible once a further understanding of the genetic influences and mechanisms in the causation of autoimmune disease is further elucidated.

Alleles↗

[Immunogenetic study of the HLA system in families of patients with ankylosing spondylitis].

In this study the immunogenetic relationships among 141 unrelated HLA-B27+ patients with ankylosing spondylitis (AS) and 792 members of their families were studied. Two control groups, with at least one B27+ parent were used (families undergoing transplantation program and triplet families undergoing paternity testing). All subjects were typed for HLA-A and -B antigens by microlyphocytotoxity test (MLCT) on local typing trays. The frequency of HLA-A and -B alleles was equal in the all tested groups. The segregation of all tested genes was regular regarding to the total number of positive and negative siblings, while regarding to the sex of sibs was irregular for HLA-B27 and -B5 gene. The statistical significance (p < 0.05) was found when ratio between B27+ and B27- sons in AS group was compared with the same ration in control families. In AS group was detected statistical significant (p < 0.01) high number of B5+ than B5- daughters and statistical significant (p < 0.05) less number of B5+ sons. HLA-B21 was shown to be decreased among B27+ AS patients. A synergistic effect between additional HLA-B alleles and B27 was not observed. The distribution of B27 haplotypes in AS and control families was similar except for haplotype HLA-A10, B27 which was significant (p < 0.001) less present in AS families.

Cytotoxicity Tests, Immunologic↗

[Immunogenetic structure of the Ukrainian White Steppe species pig herd by frequency of complex genotypes in connection with some parameters of productivity].

Studying of the structural organization of the gene pool considering frequencies of occurrence of complex genotypes in animals simultaneously by many loci of blood groups allows to better characterize immunogenetic parameters of populations and peculiarities of selection acting upon animals of different genetic classes. The data on presence of the optimum level of gene diversity and peculiarities of selection acting upon polymorphic systems of blood groups in the pig herd of Ukrainian Steppe White breed have been obtained. The results can be used for increasing efficiency of breeding.

Animal Husbandry↗

[Immunogenetics of optic neuritis in children with multiple sclerosis].

The aim of the work was to study immunogenetic peculiarities of optic neuritis in children with MS. Using PCR-SSP technique genomic typing was performed on HLA DRB1 gene (chromosome 6p21) of 56 unrelated children with ON registered at least once in clinically verified MS. 264 adult MS patients and 328 healthy controls from the same stratum of population were also genotyped. A very strong correlation of MS with DR15 (DRB1*150 ... alleles) was observed in comparison with healthy cases in the above population. In 39 cases of children with ON and MS both parents were also genotyped and the rate of their DRB1 haplotypes transmitted (patients) and non-transmitted (control cases) to their sick children were compared in accordance with affected family-based (AFBAC) method. A very strong correlation of demielinating disease with DRB1*150 ... alleles was verified. Transmission/disequilibrium test (TDT) was carried out to analyze correlation in selected families consisting of one sick child and two parents at least one of whom was heterozygous for DR15. The difference observed in transmission from these parents of DR15 alleles and alternative DRB1 alleles was extremely great providing obvious evidence for correlation of DR15 (DRB1*150...) alleles and susceptibility of children to ON and MS.

Adolescent↗

Interrelations between Immunogenetic Factors (HLA antigens) and Lymphocyte Subset Quantitative Rearrangements in Hodgkin's Disease Patients.

In this report we analyzed interrelations between cell quantity in lymphocyte subsets and lymphocyte immunogenetic (HLA) markers in 30 untreated patients with Hodgkin's disease (HD). We defined percentage and the absolute number of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD16, CD25 and CD72 markers for HD patients referring to their HLA phenotype (A, B, Cw loci and DRB1). HD patients had decreased absolute number of all the lymphocyte subsets. This was apparently associated with reduced number of peripheral blood lymphocytes, since their subset shares remained similar to those of healthy volunteers. HD patients had different HLA repertoire: some displayed simultaneous exertion of four antigens in A and B loci ("full house" patients) and others - reduced HLA repertoire ("non-full house" patients). Simultaneous analysis of lymphocyte subset rearrangements and HLA expression revealed that "full house" patients had no significant rearrangements in lymphocyte subsets, except reduced CD4(+) and increased CD25(+) lymphocytes. The reduction of expressed HLA alleles interrelated with reliable decrease of CD3(+), CD4(+), CD16(+) cells. Expression of such HLA alleles as A1, A2, B13, B16, B17, B21, B27, DR2 and DR4 also interrelated with significant decrease in some lymphocyte subsets, of which CD4(+) cells prevailed. The most distinct reduction of lymphocyte subsets interrelated with expression of B17 and DR2 HLA loci. Hence, in HD patients pathological rearrangements of lymphocyte subsets are strictly associated with their HLA expression.

Journal Article↗

[Immunogenetic studies of familial occurrence of progressive systemic scleroderma and circumscribed scleroderma].

Two different forms of scleroderma in one family are described: the mother suffers from systemic sclerosis and her daughter from linear morphoea. The observed HLA antigens indicate that systemic sclerosis and morphoea have various features in common. The immunogenetic data can be used to calculate the aetiological and preventive fractions, which together with environmental hazards and other risk factors describe the HLA-associated potential for provocation of scleroderma.

Adolescent↗

The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria.

One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. Urinary albumin excretion was measured as the albumin:creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18-2.67; p < 0.01); the relative risk of microalbuminuria (UA/UC > 3.0 mg/mmol) associated with expression of HLA-A2 was 2.52 (95 per cent CI 1.11-5.73; p < 0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p < 0.01) and expression of the HLA-A2 antigen (p < 0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC > 45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroalbuminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p < 0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure.

Adolescent↗

[Immunogenetic features of patients with ulcer disease of the stomach and duodenum and the significance of genetic markers in prognosis of complications of stomach and duodenal ulcers in Azerbaijan].

The work has shown that patients with ulcer disease of the stomach and duodenum have immunogenetic features. In particular, genetic markers were detected for ulcer disease of the stomach and duodenum whose presence allows to predict with certain probability the development of ulcer disease of the stomach and duodenum. The presence of antigen HA-At and haploids--AxB18 and HLA--A10B27 is prognostically unfavorable factors for the development of complications of this disease.

Adult↗

[The use of clinical, immunogenetic and immunological indices for predicting the development of the recurrent form of erysipelas of the lower limbs].

A consecutive alternative analysis has been carried out of clinical, immunogenetic and immunological indices in patients with primary erysipelas of the lower extremities with and no recurrences during the last 3-5 years. The authors compiled a special scale allowing precise and early prediction of unfavourable, recurrent course of primary erysipelas of the lower extremities.

Adult↗

[Immunogenetic HLA markers of chronic viral hepatitis].

AIM: To study possible immunogenetic HLA markers of chronic viral hepatitides. MATERIAL AND METHODS: Using the reaction of complement-dependent cytotoxicity by Terasaki, we analysed distribution of leukocytic HLA antigens (loci A, B and C) in 179 patients with chronic viral hepatitides B, C and D in Russians and Kazakhs living in the Astrakhan Region. RESULTS: In the Russian population we discovered a significant positive association of CVHB with HLA-B18, HLA-B35, HLA-B40, HLA-Cw3 antigens, and negative one--with HLA-A2. In Kazakhs with CVHB there was a positive association with HLA-A3, HLA-B18 and negative one--with HLA-A11. Alleles HLA-A10, HLA-B35, HLA-B40 and HLA-Cw3 mark CVHC in Russians. HLA-Cw4 specificity acts as protector in development of chronic HCV-infection. A correlation was found between carriage of some specificities and haplotypes of HLA and activity of chronic HBV and HCV infection. A high risk of chronic delta infection in Russians is associated with HLA-B8 and HLA-B35, in Kazakhs--with HLA-B35 and HLA-D40. There are significant associations between CVHB, CVHC, chronic delta infection and some HLA haplotypes. CONCLUSION: A universal role of HLA-B35 specificity in development of CVH irrespective of hepatotropic virus and patients' nationality is shown.

Chronic Disease↗

Artiodactylan phylogeny: an immunogenetic study based on comparative determinant analysis.

The phylogenetic relationships of major artiodactylan taxa were investigated by means of comparative determinant analysis (CDA). Monospecific antisera against taurine cattle albumin, transferrin, C3 and IgM were used to derive determinant formulas of their homologues in 21 species (plus 12 other mammals for outgroup comparison). Fifteen accepted mutations could be demonstrated in Artiodactyla, permitting recognition of nine immunologically defined species groups. Results with phylogenetically relevant implications include the clear immunogenetic separation of the vicugna from true ruminants, a complex pattern of accepted mutations rendering a genealogical analysis of the principal pecoran radiation difficult, one synapomorphic mutation combining the goitred gazelle with bovines but excluding Caprinae, and the immunological recognition of the three grades of wild cattle evolution. This study demonstrates the suitability of CDA as a tool of phylogenetic systematics above the level of genera.

Albumins↗

[Immunogenetic grounds for the development of local forms of primary tuberculosis in children].

The ++clinico-immunogenetic status of children with local forms of primary tuberculosis was analysed. Examination included 99 children aged 4-14 years with pulmonary tuberculosis. The control group comprised 51 children who has negative tuberculin tests and no intercurrent diseases. The HLA composition was determined by the A, B, C and DR loci. The HLA-DR2 representation is responsible for a high specific process risk and HLA-A11 and HLA-B15 can be characterized as antigens causing a resistance to tuberculosis infection.

Adolescent↗

[Immunogenetic mechanism of Behçet's disease].

In order to investigate the immunogenetic mechanism of Behçet's disease, frequencies of HLA antigens were studied in patients. The subjects consisted of 66 patients and 99 normal controls. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR, -DQ antigens. HLA-DP antigens were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant increase of HLA-B15 was observed in the patients. In contrast, no significant difference was observed in HLA-Bw52 which possesses only two different amino acids from HLA-B15. On the contrary, frequencies of HLA-A11, HLA-Aw33, HLA-B35, HLA-B44 and HLA-DQw1 were significantly lower in the patients than in the controls. No significant difference was observed in HLA-DP antigens. These results suggest that Behçet's disease involves both disease susceptibility factors and disease resistance factors and that such genetic factors are mapped within or very close to the HLA-B gene in the class I gene region. Additionally class II HLA-DQ antigen is associated with disease resistance factors.

Amino Acid Sequence↗

Immunogenetic markers for autoimmune diseases of the endocrine system.

New immunogenetic markers are demonstrated for type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. These markers are detected by restriction fragment length polymorphism (RFLP) analysis of HLA-D region genes and genes for the tumor necrosis factor alpha (TNF alpha). By analysing haplotypes transmitted to diabetic probands in families and comparing them with haplotypes that are only transmitted to healthy siblings it is shown that DQw8-DQB1 gene variation is important for susceptibility on DR4 haplotypes. Analysis of this DQw3 split in patients with Hashimoto's thyroiditis reveals that the other DQB1 gene variation, namely DQw7, displays the strongest association with Hashimoto's thyroiditis. This DQB1 variation has several implications for susceptibility and/or pathogenesis of both autoimmune endocrine diseases. Novel polymorphisms for TNF alpha are detected and it is shown that heterozygosity for TNF polymorphisms is significantly associated with type I diabetes and Graves' disease. Furthermore, DR4 haplotypes transmitted to diabetic probands possess significantly more the 10.5 Kb fragment in contrast to DR4 haplotypes transmitted only to healthy family members. This genetic polymorphism raises functional issues in susceptibility to autoimmune disease and can lead to a new explanation of the enigmatic HLA-association with a variety of diseases.

Diabetes Mellitus, Type 1↗