Immunogenetics in pathogenesis of and protection against toxoplasmosis.
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Animals↗
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Immunogenetic studies on HLA-DR in German coal miners with and without coal worker's pneumoconiosis.
Coal worker's pneumoconiosis is caused by the pulmonary deposition of coal dust, including silica particles. Several factors such as chemical composition and physical properties of silica-containing dust, particle size distribution, intensity, and duration of exposure influence the disease development. Genetic factors may also be involved. To define whether HLA-DRB may function as a genetic factor for predisposition to coal worker's pneumoconiosis, we determined DRB1, 3, 4, 5 alleles. For this purpose, DRB typing with sequence-specific oligonucleotide probes in 204 German miners with pneumoconiosis and in 52 German miners without pneumoconiosis was used. The miners had worked under comparable conditions. The frequency of DR8 (1*0801-0804) was increased in patients developing pneumoconiosis during the first 15 years of mining (p = 0.047). The frequency of DR1 (1*0101-0103) was elevated (p = 0.022) and that of DR52 (3*0101, 3*0201, 3*0202, and 3*0301) was reduced (p = 0.026) in miners without pneumoconiosis. Our data show that the presence of DR1 and the absence of DR52 support the resistance to coal worker's pneumoconiosis. Furthermore, DR8 may be involved in the rapid development of coal worker's pneumoconiosis.
Adult↗
Immunogenetics of multiple sclerosis and optic neuritis: DNA polymorphism of HLA class II genes.
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Alleles↗
Immunogenetics of human minor histocompatibility antigens: their polymorphism and immunodominance.
Minor Histocompatibility (mH) antigens are polymorphic endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex molecules. In transplant situations where tissue donor and recipient are matched for HLA, mH antigens may trigger strong cellular immune responses. To gain insight into the polymorphism of mH antigens we studied their frequencies in the healthy population. Five HLA class I restricted mH antigens recognized by distinct cytotoxic T-cell (CTL) clones were used in the population genetic analysis consisting of a panel (N = 100) of HLA typed target cells. Three mH antigens showed phenotype frequencies of 69% or higher, this contrasted the frequencies of two other mH antigens with 16 and 7% respectively. To gain insight into the "functional" polymorphism of the T-cell response to mH antigens, we analyzed the specificity of CTL clones within individuals. Three out of five individuals investigated shared a CTL response to one single HLA-A2 restricted mH antigen. These results indicate limited allelic polymorphism for some mH antigens in the healthy population and are suggestive of the existence of immunodominant human mH antigens.
Alleles↗
Immunogenetic basis of myocarditis: role of fibrillary antigens.
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Actins↗
Ancestral haplotypes reveal the role of the central MHC in the immunogenetics of IDDM.
The major histocompatibility complex (MHC) contains multiple and diverse genes which may be relevant to the induction and regulation of autoimmune responses in insulin dependent diabetes mellitus (IDDM). In addition to HLA class I and II, the possible candidates include TNF, C4, and several other poorly defined polymorphic genes in the central MHC region. This study describes two approaches which take advantage of the fact that the relevant genes are carried by highly conserved ancestral haplotypes such as 8.1 (HLA-B8, TNFS, C4AQ0, C4B1, DR3, DQ2). First, three "diabetogenic" haplotypes (two Caucasoid and one Mongoloid) have been compared and it has been shown that all three share a rare allele of BAT3 as well as sharing DR3, DQ2. In 43 sequential patients with IDDM the cross product ratio for BAT3S was 4.8 (p less than 0.01) and 6.9 for HLA-B8 plus BAT3S (p less than 0.001). Second, partial or recombinant ancestral haplotypes with either HLA class I (HLA-B8) or II (HLA-DR3, DQ2) alleles were identified. Third, using haplotypic polymorphisms such as the one in BAT3, we have shown that all the patients carrying recombinants of the 8.1 ancestral haplotype share the central region adjacent to HLA-B. These findings suggest that both HLA and non-HLA genes are involved in conferring susceptibility to IDDM, and that the region between HLA-B and BAT3 contains some of the relevant genes. By contrast, similar approaches suggest that protective genes map to the HLA class II region.
Adult↗
Pre-type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity.
In an ongoing prospective study 32 individuals have been evaluated for insulin secretory dynamics, islet cell antibodies and HLA antigens, during the preclinical phase of Type 1 diabetes mellitus. Twenty-four out of the 32 subjects were islet cell antibody-positive. To date, 14 subjects (10 islet cell antibody-positive, four islet cell antibody-negative) have progressed to develop overt diabetes. Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). Irrespective of differences in islet cell antibody status or HLA-DR alleles, pre-diabetic individuals exhibited a similar slow course of progressive beta-cell dysfunction.
Adolescent↗
Genetic loci of components of the classical and alternate pathway of complement activation: a new dimension of the immunogenetic linkage group (HLA) on chromosome 6 in man.
In this review, a working hypothesis is put forward that functional cooperation of various types of cells and proteins in immune recognition, mediation and response is maintained by a common chromosomal region which evolved over millions of years from a common ancestor by gene duplication. In brief, the known functions of the H-2 complex are discussed (susceptibility and resistance to viral infection, immune response genes, T-B cell interaction as non-self recognition and response). The addition of loci of the classical and alternate pathway of complement activation to the HLA region (i.e., C2, C4 and the Bf system) is reviewed with respect to functional relationship to immune recognition and mediation mechanisms. As expected according to this hypothesis, genes for late-acting components (C3, C5, C7 and C8 in man, C5 in mice) have so far not proved to be linked to HLA.
Animals↗
An immunogenetic analysis Skn antigens in mice.
Studies on the fate of Skn-incompatible grafts indicate that both the immune response to and the potency of these antigens are influenced by the MHC. Evidence is also presented that strains CBA, C3H, and A possess different Skn antigens.
Aging↗
Immunogenetic basis for immunologic privilege in the anterior chamber of the eye.
DBA/2 mastocytoma (P815) cells are able to grow when inoculated into the anterior chamber of eyes of histoincompatible mice. Tumor growth is unrestrained in recipient mice differing from the DBA/2 strain at multiple minor H loci, but sharing the H-2d haplotype; progressive tumor growth in these animals involves the entire eye, invades the orbit and kills the hosts by extension into the cranial vault. Alternatively, P815 cells grow initially but are unable to sustain continued growth in the anterior chambers of recipient mice differing from DBA/2 at the H-2 complex. Recipients differing from DBA/2 at either the K or D regions of H-2 develop anti-DBA/2 immunity that destroys the intraocular tumor within 20 days of inoculation. Severe inflammatory reactions in these eyes produce "innocent bystander" destruction of ocular tissue and produce blindness. Recipients differing from DBA/2 at both K and D regions of H-2 also mount vigorous anti-DBA/2 immunity that destroys the intraocular tumor. In these instances, the nonspecific component of the rejection reaction is minimal: when the tumor cells are destroyed, the eyes are restored to anatomic and functional integrity. These results indicate that immunologic privilege in the anterior chamber of the eye is afforded to allogeneic tissues to varying degrees depending upon allodisparity at H-2 loci encoding class I MHC products. The results further imply that the precision of the alloimmune response may be under the control of these same MHC products.
Animals↗
Immunogenetic aspects of in vivo allotolerance induction during the ontogeny of Xenopus laevis.
This study describes the ontogeny of allograft immunity in a partially inbred strain of frogs (Xenopus laevis). At various times during the frogs' premetamorphic, perimetamorphic, and postmetamorphic life, major histocompatibility complex (MHC) homozygous strain JJ Xenopus (MHC haplotype j) were grafted with skin from adult donors of defined MHC homozygous (j,f) and heterozygous (j/f,f/h) haplotypes. This protocol reveals that destructive allograft reactivity to MHC alloantigens in Xenopus matures slowly and that allotolerance can be induced to such MHC-encoded antigens throughout larval life. The ultimate fate of an MHC disparate transplant (survival or rejection) is dependent on several interacting variables, which include antigen dose, haplotype dose, and the developmental stage of the host frog at the time of transplantation. In contrast, minor H-locus disparate (MHC compatible) grafts never appear to be rejected by hosts grafted at any larval stage.
Age Factors↗
Immunogenetic analysis of rat strains with recombinations in different regions of the MHC.
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Animals↗
Regulation of the neutral phosphatase in Chlamydomonas reinhardi: an immunogenetic study of wild-type and mutant strains.
In Chlamydomonas reinhardi, the activity of the neutral phosphatase considerably increases when the cells are grown in the absence of inorganic phosphate (Pi). A comparative immunological study of cells grown on media containing Pi or not indicated that the neutral phosphatase was synthesized de novo. Ten mutants lacking the neutral phosphatase and distributed among three genetic loci (PD2, PD3, PD24) were investigated for their ability to produce cross-reacting material (CRM) antigenically related to the wild enzyme. All mutants were shown to form much less CRM than the wild-type strain. It is proposed that the three genes are involved in the regulation of neutral phosphatase synthesis.
Antigens↗
Immunogenetic study on the polymorphism of serum alpha2-lipoproteins in mink. I. Identification and genetic control of five Lpm allotypes.
Five allotypes, Lpm 1, Lpm 2, Lpm 3, Lpm 4, and Lpm 5, were detected by isoimmunization in mink sera. Immunoelectrophoresis, preparative ultracentrifugation, and histochemical tests for lipids and esterase permitted reference of these alloantigenic markers to a very high density alpha2-lipoprotein. Based on population analysis and breeding tests, five genetic units are postulated: Lpm1, Lpm4, Lpm3,4, Lpm1,2, and Lpm2,4,5. These units determine the polymorphism of the Lpm system and behave as Mendelian alleles.
Alleles↗
Immunogenetic study on the polymorphism of serum alpha 2-lipoprotein in mink. III. Ld1 allotype of low-density lipoprotein.
Mink Ldl antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ldl and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data.
Animals↗
Immunogenetic study on the polymorphism of serum alpha 2-lipoproteins in mink. IV. Diallelism at the Ld locus of low-density lipoprotein.
Antibodies against a new allotype, Ld2, of mink low-density lipoprotein (LDL) were obtained by alloimmunization with a preparation of this lipoprotein. The two known allotypes of LDL, designated Ld1 and Ld2, are coded for by codominant alleles of the autosomal Ld locus. This locus is probably involved in the genetic control of the whole serum pool of LDL molecules. In Ld1/Ld2 heterozygotes, LDL is represented by two homozygous types of molecules, Ld1 and Ld2; it has no hybrid molecules bearing both allotypic specificities together. The results suggest that the Ld locus has, presumably, only two alleles in the mink populations studies. Mink LDL having allotypes Ld1 and Ld2 was found to be homologous to human and pig LDLs. Antigenic specificity of Ld1 allotype was established in the sera of a wide phylogenetic range of mammals and in the human LDL. The parallelism between the phylogenetic antiquity of the Ld1 gene and its high frequency in mink and other species may be attributed to the selective value of this gene, which has been retained unaltered during macroevolution.
Alleles↗
Reiter's disease in northern India. A clinical and immunogenetic study.
Thirty-six patients fulfilling the criteria for Reiter's disease were studied (29 men and 7 women; 4:1). The mean age of onset was 23.8 years; in 75% of patients the onset was in the second and third decades. Clinical manifestations included low back pain and stiffness (69%), non specific urethritis (53%), heel pain (44%), radiographic sacroiliitis (42%), conjunctivitis (39%), dysentery and diarrhoea (33%), mucosal ulcerations (17%) kidney disease (14%), anterior uveitis (19%), and keratoderma blennorrhagicum (8%). Peripheral arthritis was mono or oligoarthritis in 58% of patients, mainly affecting the large joints of lower extremities, and it was often asymmetric (mean degree of asymmetry = 0.37). HLA-B27 antigen was detected in 83% of 36 patients compared with 5.9% of 118 controls (relative risk 79, corrected Fisher's P = 7.719E-18).
Adolescent↗
Clinical and immunogenetic studies in rheumatoid arthritis from northern India.
A total of 258 patients with classic rheumatoid arthritis seen over a 7-year period were included in this study. The majority of the patients had relatively mild disease at the time of presentation. The incidence of extraarticular manifestations such as subcutaneous nodules, vasculitis, amyloidosis and pulmonary involvement was low although one or two pulmonary function test parameters were abnormal in some. Seventy patients were tested for all three subclasses of rheumatoid factors - IgM, IgG and IgA. Of these, 23 patients had all three whilst four had only IgG. The 62 patients who had most typical and severe manifestations were typed for four major HLA loci A, B, C and DR. Of these 42 (67.7%) had DR4 antigen while DR3 antigen was detected in 14 (22.6%).
Adult↗