Immunogenetics. Viruses, cancer and the MHC.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “immunogenetics”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Immunogenetics. Female anti-male attack.
Explore the source record for details and available documents.
Animals↗
Immunogenetics. Soaring costs in defence.
Explore the source record for details and available documents.
Animals↗
The immunogenetics of insulin-dependent diabetes.
Insulin-dependent (type 1) diabetes mellitus (IDDM) is a multifactorial disease with a strong genetic component. The majority of the genetic component can be explained by associations between IDDM and genes in the major histocompatibility complex (MHC). The best single marker for IDDM is based on amino acid polymorphism of the HLA-DQ gene. Current evidence, however, indicates that the MHC susceptibility to IDDM is determined by a combination of HLA class I, II and III genes contained on HLA haplotypes. A non-MHC genetic component to IDDM also exists. To date, the most consistent association is between IDDM and markers of the insulin gene locus.
Diabetes Mellitus, Type 1↗
Immunogenetic aspects of primary IgA nephropathy.
Explore the source record for details and available documents.
Adult↗
Clinical, histopathological, and immunogenetic analysis of ocular adnexal lymphoproliferative disorders: characterization of malt lymphoma and reactive lymphoid hyperplasia.
Malignant lymphomas and reactive lymphoid hyperplasia (RLH) in the ocular adnexa are sometimes difficult to differentiate morphologically and have often been categorized together as a lymphoproliferative disorder. Immunogenotypic characters of these diseases have not yet been well clarified. This study included 76 cases of ocular adnexal lymphoproliferative disorders. These consisted of 52 cases of malignant lymphoma (43 primary and 9 secondary), 22 of RLH, and 2 borderline cases. There were slightly more male than female subjects. Diagnoses were based on morphology and immunophenotypic characteristics. Clonalities were detected by means of polymerase chain reaction (PCR), and immunoglobulin heavy-chain variable region (VH) genes were sequenced in 10 cases of mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma constituted 86% (37 cases) of the primary lymphomas. MALT lymphomas were more indolent, more rarely disseminated, and had a lower death rate than the other primary lymphomas. Two patients exhibited coexistence of MALT and diffuse large B-cell lymphoma. The average age of patients with RLH was 5.5 years younger than that of those with MALT lymphoma. One of the cases of RLH later progressed to malignant lymphoma. B-cell clonality was detected by PCR in 57%, 55%, and 0% of primary lymphomas, MALT lymphomas and RLHs, respectively. Sequencing of VH genes revealed that the VH3 family was the most commonly expressed germline VH family (70%) and that DP-63, DP-54 and DP-47 genes were frequently found in the MALT lymphomas examined. PCR analysis was useful for differentiation between MALT lymphoma and RLH. Sequence analysis of VH genes showed that an autoimmune mechanism may be involved in the lymphomagenesis of ocular adnexal MALT lymphoma.
Adult↗
The immunogenetics of asthma and eczema: a new focus on the epithelium.
Asthma and eczema (atopic dermatitis) are the most common chronic diseases of childhood. These diseases are characterized by the production of high levels of immunoglobulin E in response to common allergens. Their development depends on both genetic and environmental factors. Over the past few years, several genes and genetic loci that are associated with increased susceptibility to asthma and atopic dermatitis have been described. Many of these genes are expressed in the mucosa and epidermis, indicating that events at epithelial-cell surfaces might be driving disease processes. This review describes the mechanisms of innate epithelial immunity and the role of microbial factors in providing protection from disease development. Understanding events at the epithelial-cell surface might provide new insights for the development of new treatments for inflammatory epithelial disease.
Animals↗
Getting under the skin: the immunogenetics of psoriasis.
Psoriasis is a chronic inflammatory disorder of the skin that is mediated by T cells, dendritic cells and inflammatory cytokines. We now understand many of the cellular alterations that underlie this disease, and genomic approaches have recently been used to assess the alterations of gene expression in psoriatic skin lesions. Genetic susceptibility factors that contribute to predisposition to psoriasis are now also being identified. It is hoped that we will soon be able to correlate the cellular pathogenesis that occurs in psoriasis with these genetic factors. In this Review article, we describe what is known about genes that confer increased susceptibility to psoriasis, and we integrate this with what is known about the molecular and cellular mechanisms that occur in other inflammatory and autoimmune disorders.
Animals↗
Lichen sclerosus premenarche: autoimmunity and immunogenetics.
Lichen sclerosus is among the most frequently seen paediatric vulval disorders. In adults a strong association between lichen sclerosus and autoimmune diseases, and also with HLA class II locus DQ7, has been well demonstrated in women and a weaker association in men. These associations have not previously been studied in children, although in other autoimmune diseases, the HLA associations have been strongest in children. We performed HLA tissue typing and looked for autoimmune associations in a group of 30 children with vulval lichen sclerosus. HLA DQ7 was present in 66% of female children with lichen sclerosus compared with 31% in controls. Previous studies reported DQ7 in 51% of adult female patients and 45% of male patients. Sixteen per cent of the children were homozygous for DQ7 as opposed to 5% of controls. In the childhood group, only 4% had another autoimmune disease, but 56% of their parents or grandparents did. Age differences make comparison difficult, but the family history of autoimmunity appears to be strong in the early-onset group, in addition to the stronger association with DQ7.
Adolescent↗
Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.
BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.
Adolescent↗
Immunogenetic risk factors for anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis.
Wegener's granulomatosis (WG) and microscopic polyangiitis are systemic autoimmune diseases characterized by the presence of ANCA in the sera of patients. Little is known about the aetiologic factors and genetic predisposition as well as the pathogenesis of these disease entities. A slightly decreased representation of HLA-DRB1*13 and HLA-DQB1*0603 individuals was observed in our cohort of ANCA-associated systemic vasculitis (AASV) patients compared with controls. In addition, HLA-DRB1*04 individuals were over-represented in a subgroup of patients with WG in end-stage renal disease as a result of renal vasculitis. In order to identify other genes relevant for these diseases, we investigated highly polymorphic markers in the vicinity of several immunorelevant genes, i.e. tumour necrosis factor (TNF)alpha, IL-2, IL-5 receptor alpha (IL-5RA), in a group of 102 patients with AASV and compared the representation with controls. Furthermore, functional polymorphisms were directly analysed in the promotor region of TNFalpha as well as in the coding region of the FcgammaIIRA genes. Polymorphisms of the TNFalpha promotor (TNF-308) as well as in the FcgammaIIRA gene were excluded as risk factors for the disease in our cohort. No major phenotype distribution differences were observed between patients and controls for the IL-2 and IL-5RA microsatellites. Most importantly, several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)-ANCA+ AASV. Thus, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASV patients.
Adolescent↗
Hyperprolactinaemia in patients with heart failure: clinical and immunogenetic correlations.
BACKGROUND: Prolactin represents a stimulatory link between the neuroendocrine and immune systems, but its involvement in the neurohumoral adaptations to heart failure (HF) has not been explored. METHODS: We prospectively studied 55 patients (45 males, 10 females, age 48 +/- 7 years) with NYHA Class II/III HF due either to dilated cardiomyopathy (CMP) (n = 33) or ischemic heart disease (IHD) (n = 22). Serum prolactin levels were determined by radioimmunoassay, soluble interleukin-2 receptor (sIL-2R) levels by enzyme-linked immunoassay and HLA-DQ genotyping with PCR. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDd) were assessed echocardiographically. RESULTS: Hyperprolactinaemia (17.3 +/- 4 ng mL-1 [Group I] vs. 4.64 +/- 2 ng mL-1 [Group II], P < 0.01) was found in 14 patients (8 with IHD, 6 with CMP). The distribution of HLA-DQB1 alleles was compared in the two groups and showed a significant increase in the frequency of *0301 (86% in Group I vs. 45% in Group II, P < 0.05). Histidine at position 30 of the HLA-DQB1 gene was found in 22% of Group II but in none of Group I patients. Furthermore, there was an inverse correlation between the presence of histidine at position 30 and the levels of serum prolactin. Both sIL-2R levels, a marker of T-cell activation, and concanavalin A-stimulated lymphocyte proliferation were lower in Group I patients (561 +/- 106 vs. 804 +/- 109 pg mL-1 and 20.8 +/- 4 vs. 37.3 +/- 5 cpmX103 [3H] thymidine, respectively). LVEF was significantly higher (32 +/- 5%) and LVEDd smaller (62.0 +/- 6 mm) in Group I compared to Group II (25 +/- 4% and 68.0 +/- 5 mm, respectively, P < 0.01) patients. CONCLUSION: Hyperprolactinaemia presents in 25% of patients with HF and may reflect decreased activation of T-lymphocytes associated with relatively preserved LV systolic function which is under immune-genetic control at the HLA-DQ locus.
Adult↗
Immunogenetics of Henoch-Schoenlein disease.
In order to investigate the genetic basis of susceptibility to Henoch-Schoenlein purpura (HS), blood samples of 152 patients, 105 of whom had renal disease, were collected in a two-step study. The evaluation of DRB, DQB and DQA polymorphism was done by analysis of the restriction polymorphisms produced by TaqI enzyme. DRB1*07 was less frequent in patients than in the control group (gene frequency 0.09 and 0.18, respectively; P = 0.0023), whereas 64% of the patients were positive for DRB1*01 and/or DRB1*11 compared with 48% of the control group (P = 0.0069). Polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) typing of DRB1*01- and DRB1*11-positive individuals did not show any deviation of frequencies of DRB1*01 subtypes between patients and controls, whereas among DRB1*11 subtypes DRB1*1104 was significantly increased in the patients (Pc = 0.033). The comparison between patients with renal disease and those without renal disease showed no significant differences in the frequency of the single DRB, DQB and DQA alleles. The study of restriction polymorphisms in the switch region of the constant genes alpha 1, alpha 2 and mu of the heavy chains of immunoglobulins, using the enzyme Sacl and a specific probe, did not show any difference between 44 patients and 54 controls. This study demonstrates that susceptibility to HS also has a genetic origin: on one hand, the presence of DRB1*01 or DRB1*11 makes disease onset easier; on the other hand, DRB1*07 could induce some resistance to the disease. It is suggested that, as well as for other diseases caused by an impaired immune response, single amino acids in a key position in the HLA-DRB molecule make it more or less easy to recognize some antigenic peptide, towards which an immune response leading to disease is triggered.
Adolescent↗
Immunogenetics of the rare HLA-B allele B*4408.
The nucleotide sequence of exons 2 and 3 of B*4408 has been confirmed. This allele has now been found in five, apparently unrelated, north-western European Caucasoid subjects, residing in Wales, on HLA haplotypes bearing: A*0201, Cw*0501 with DRB1*0401, DQA1*03, DQB1*0301 in four instances and DRB1*0701, DQA1*0201, DQB1*0202 in one instance. The unique serological reactivity of 'HLA-B44BO' was established using up to nine B*4408 subjects and was easily identified using a variety of B44 and B62 antisera. The phenotype and gene frequencies of B*4408, in a sample of 40 473 subjects residing in Wales, were 0.01235% and 0.00006, respectively.
HLA-B Antigens↗
Immunogenetics in PSC.
Primary sclerosing cholangitis (PSC) does not exhibit simple Mendelian inheritance attributable to a single gene locus and our knowledge of the genetics of this complex disease is based entirely on case-control studies of candidate genes. The prime candidates in PSC are inherited variation (polymorphism) in the genes that regulate the immune response, especially the genes of the major histocompatability complex (MHC). Thus far, five different human leukocyte antigen (HLA) haplotypes have been associated with PSC: three with increased risk of disease and two with reduced risk. More recently studies of non-MHC genes have failed to associate PSC with several cytokine genes (IL-1 and IL-10), with FAS (TNFRSF6), with TGFbeta-1, or with CCR-5 but have found genetic links with MMP-3 and disease progression, whilst the potential role of CTLA-4 gene polymorphism remains in question. With the completion of the human genome project, understanding the genetics of complex (non-Mendelian) disease is a major priority for the research community and the studies summarized herein may guide these future investigations.
Cholangitis, Sclerosing↗
Pathogenesis: immunogenetic factors.
The occurrence, albeit infrequent, of systemic vasculitis in closely related family members suggests that both environmental and genetic factors may play a role in the pathogenesis of these diseases. Malfunction of immune regulation in the systemic vasculitides may indicate a role for genes that encode molecules critical to the immune responses. The extremely polymorphic sequences of MHC molecules may provide a structural basis for associations of MHC genes and systemic vasculitis. This review summarizes recent reports of MHC associations, mechanisms by which MHC may play a role in certain vasculitides, and also examines the role for genes encoding non-MHC molecules, such as Fcgamma receptors, cytokines and T cell co-stimulators. Data suggest that the pathogenesis of systemic vasculitides such as giant-cell arteritis, Takayasu's arteritis and Wegener's granulomatosis might be governed by multiple genes encoding host defence molecules, in conjunction with environmental factors.
Cluster Analysis↗
The immunogenetics of thyroid-associated orbitopathy.
Explore the source record for details and available documents.
Abatacept↗
[Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. 2. Immunogenetic characterization of T-cell receptor-positive tumor-infiltrating lymphocytes and survival of patients with necrotizing melanomas of the choroid].
BACKGROUND: T-cell receptor (TCR) gene analysis of tumor infiltrating lymphocytes (TIL) has been recognized to play a pivotal role in the immunosurveillance of solid neoplasms. PATIENTS AND METHODS: Therefore, 113 necrotizing choroidal melanomas (NMM) were compared to 100 non-necrotizing melanomas (MM) histologically and immunohistochemically. RESULTS: NMM showed TIL more frequently (76.11% vs. 21%, p < 0.001). V alpha/V beta- (70.3% of NMM) and V gamma 1- (39.2% of NMM) and V delta 1- (52.7% of NMM) TCR+ cells were distributed focal or diffuse, and correlated with tumor volume, diameter, and scleral invasion. 74.33% of NMM patients had died after 240 months (5 year survival: 58.1%). Mortality was not significantly associated with TIL (p < 0.33) or V alpha/V beta-TCR+ cells (p < 0.2), however, survival was significantly increased with evidence of V gamma 1- and V delta 1-TCR+ cells (p < 0.026). CONCLUSIONS: V alpha/V beta-, V gamma 1- and V delta 1-TCR+ tumor infiltrating lymphocytes can be demonstrated in choroidal melanomas. This is a basis for functional studies providing a rationale for the evaluation of immunotherapeutic modalities.
Adult↗