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At least 397 records · Page 22Linked to original sources
PubMed2001

Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data.

Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants of longevity resides in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, studies performed on mice have suggested that the Major Histocompatibility Complex (MHC), known to control a variety of immune functions, is associated with the life span of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA (the human MHC) genes on human longevity by comparing HLA antigen frequencies between groups of young and elderly persons have been published, but conflicting findings have been obtained. In fact, the same HLA antigens are increased in some studies, decreased in others and unchanged in others. On the whole, that could lead us to hypothesize that the observed age-related differences in the frequency of HLA antigens are due to bias. In our opinion, this hypothesis is real for most studies owing to major methodological problems. However, some studies that do not meet these biases have shown an association between longevity and some HLA-DR alleles or HLA-B8,DR3 haplotype, known to be involved in the antigen non-specific control of immune response. Thus, HLA studies in man may be interpreted to support suggestions derived from the studies on congenic mice on MHC effects on longevity. However, in mice the association may be by way of susceptibility to lymphomas whereas, in human beings, the effect on longevity is likely, via infectious disease susceptibility. Longevity is associated with positive or negative selection of alleles (or haplotypes) that respectively confer resistance or susceptibility to disease(s), via peptide presentation or via antigen non-specific control of the immune response.

Aging↗
PubMed1994

An immunogenetic analysis of T-cell reactive regions on the major allergen from the house dust mite, Der p I, with recombinant truncated fragments.

Proliferation assays were used to localize the T-cell reactive sites on the major allergen from the house dust mite Dermatophagoides pteronyssinus, Der p I. Seven overlapping recombinant fragments of the Der p I molecule, synthesized with the pGEX expression vector system, were used to stimulate peripheral blood lymphocytes from 35 HDM-sensitive individuals. The fusion fragments were from 39 to 114 amino acids in length and spanned the entire Der p I molecule. Significant proliferative responses to one or more of the fragments were evident in 18 of the allergic individuals, and each of the fragments led to T-cell stimulation in at least one of the subjects. Although T-cell reactive regions were located throughout the molecule, in 12 of the 18 responsive individuals, major immunogenic sites were contained within the 56 amino acids of the N-terminus, and in 11 of these individuals T-cell reactive regions were only present between amino acid positions 1 and 94. In two individuals reactive sites could be mapped in the C-terminal half of the molecule, and in five subjects, epitopes were present in both N- and C-terminal regions. HLA class I and class II DR and DQ specificities were determined serologically in 16 of the 18 individuals, and no strong pattern of association between HLA type and the T-cell immunogenic region could be detected.

Animals↗
PubMed1998

Immunogenetic analysis of Takayasu arteritis in Indian patients.

The distribution of HLA-A, B, C and DR antigens was determined in a cohort of 104 unrelated Indian patients with Takayasu arteritis (TA) belonging to the North Indian states of Punjab, Haryana, Uttar Pradesh and Delhi. The data was compared with healthy controls belonging to the same ethnic group. In addition, polymorphism in the MHC class I chain related A (MIC A) gene was studied in a group of 25 TA patients and 40 healthy controls. The data revealed a strong association of the disease with HLA-B5 (chi2=22.5, P<1 x 10(-6), RR=3.08) as well as its two common serological subtypes, B51 (chi2=20.5) and B52 (chi2=18.5). No particular association was observed with any of the five alleles of the MIC A gene, nor any linkage disequilibrium could be established with these alleles and those of HLA-B locus in this population. The observation suggest that HLA linked genes are definitely involved in the development of Takayasu arteritis and that the disease in Indian subjects is associated with HLA-B5 and its two serological subtypes, B51 as well as B52.

Adolescent↗
PubMed1998

Immunogenetic analysis of a panel of monoclonal IgG and IgM anti-PDC-E2/X antibodies derived from patients with primary biliary cirrhosis.

BACKGROUND/AIMS: Autoantibodies with specificity for the E2 component of the pyruvate dehydrogenase complex (PDC-E2) are commonly present in primary biliary cirrhosis. The aim of this study was to generate and characterise human anti-PDC-E2 monoclonal antibodies and analyse immunoglobulin gene usage and mutation for clues to pathogenesis. METHODS: Peripheral B-lymphocytes from two patients with primary biliary cirrhosis were used to generate heterohybridomas secreting PDC-E2 specific monoclonal antibodies. The antibodies were characterised by ELISA, immunoblotting, indirect immunofluorescence and enzyme inhibition techniques, and their encoding immunoglobulin genes were amplified, cloned and sequenced. RESULTS: Four IgGlambda and one IgMlambda monoclonal antibodies specific for PDC-E2 were generated: all gave bands at 74 kD and 52 kD on PDC immunoblots, two clones were specific for the lipoylated inner lipoyl domain, and all inhibited target enzyme function. Sequence analysis suggested unrestricted VH gene usage, but a strong preference for lambda light chains. The extent of somatic mutation was high (3-20%), with evidence for antigen selection in 3/5 VH sequences. CONCLUSIONS: These monoclonal antibodies closely resemble the hallmark autoantibodies of primary biliary cirrhosis. Their specificities demonstrate true cross reactivity between an epitope on PDC-E2 and Protein X, and the existence of a subset of B cells that recognise only the lipoylated form of the antigen. The pattern of immunoglobulin gene mutations suggests an antigen-driven selection of high affinity IgG autoantibodies, supporting a possible role for exogenous antigen in the pathogenesis of primary biliary cirrhosis.

Amino Acid Sequence↗
PubMed2002

Immunogenetic selection of donors for haematopoietic stem cell transplantation: an approach.

Histocompatibility between the patient and his donor is a prerequisite for the success of transplantation of haematopoietic stem cells (HSCT). Histocompatibility testing is clinically performed by HLA typing. HLA typing can be highly informative if performed in families. In this case, comparatively little typing effort often allows to predict the identity of whole HLA haplotypes. HLA typing becomes more demanding, however, if unrelated individuals have to be considered as donors. Given the huge diversity of HLA molecules the answer to the question, whether patient and donor possess 'matched' HLA types requires considerable typing effort. Interaction between the HLA typing laboratory and the clinician is highly needed. It has to be agreed upon what loci are considered relevant and what degree of resolution is necessary. Furthermore, a strategy has to be developed, which ensures that a maximum of potential donors are tested in a reasonable time frame avoiding at the same time a work-overload of the laboratory and an excessive uneconomical typing effort. At present, experience with HSCT with unrelated donors is limited. So there is no consent on the 'correct' way of choosing unrelated donors. Each transplantation centre will have its own characteristic needs, resources, manpower and skills; therefore, the ways vary between centres. I want to present the approach in Vienna.

Alleles↗
PubMed2003

Immunogenetics of the response to HBsAg vaccination.

The major envelope protein of the hepatitis B virus (HBV), the HBsAg, constitutes the current preventative vaccine, which represents the first subunit viral vaccine developed. The genetics of the immune response to HBsAg has been extensively studied both in humans and mice. Murine studies begun over 20 years ago indicated that at least two MHC class II and one MHC class III genes regulate anti-HBs immune responses. Additional MHC-linked genes influence the immune responses to the higher molecular weight (pre-S) components of the HBV envelope. The murine studies predicted even more complex MHC gene regulation of human immune responses to the HBsAg and that complexity certainly has been demonstrated during the ensuing years. This brief review is an attempt to summarize our current understanding of the MHC genes that influence the immune response to the HBsAg and possible mechanisms of action.

Animals↗
PubMed2002

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Alleles↗