Experimental and clinical immunogenetics最新文献

The 'Human Immunoglobulin Heavy Diversity (IGHD) and Joining (IGHJ) segments', fifth report of the 'IMGT Locus on Focus' section, comprises six tables entitled: (1) 'Human germline IGHD segments at 14q32.33'; (2) 'Human IGHD alleles'; (3) 'Human germline IGHJ segments at 14q32.33'; (4) 'Human IGHJ alleles'; (5) 'Human germline IGHD orphons on chromosome 15 (15q11.2)'; (6) 'Correspondence between the different human IGHD nomenclatures', and two figures: (1) 'Protein display of human IGH D-REGIONs'; (2) 'Protein display of human IGH J-REGIONs'. These tables and figures are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cnusc.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

Studies performed in subtropical populations have found significant association between the phenotype multiple sclerosis (MS) and the major histocompatibility complex (MHC). We present the results of a case-control study conducted on a tropical population (Antioquia, Colombia) in order to detect a possible association between MS and HLA DQalpha (HLA DQA1*) alleles. Forty chromosomes belonging to MS patients were compared to two sets of controls (40 and 910 chromosomes, respectively). The HLA DQA1*0101 and DQA1*0102 alleles were found in a significantly higher proportion among the cases than among the controls, whereas the HLA DQA1*0103 allele was found in a significantly lower proportion of the cases. These results suggest that the association of HLA DQA1*0101, DQA1*0102 and DQA1*0103 to the MS phenotype found in Caucasian subtropical populations remains in individuals with MS inhabiting the tropics. This finding could mean that the major genetic component associated to the MHC in subtropical populations is the same in the tropics.

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.

The human complement factor I (IF) polymorphism has been analysed by polyacrylamide gel isoelectric focusing electrophoresis of neuraminidase-treated EDTA plasma samples followed by immunoblotting and enzymatic detection. In a population study among 121 random individuals from Chengdu, PR China, three different common phenotypes were observed. The results show that IF is polymorphic in the Chinese population. The allele frequencies were as follows: FI*A = 0.153, FI*B = 0.847. The distribution of observed phenotypes was in accordance with the Hardy-Weinberg equilibrium. In comparison to other Asian population studies, the frequency of the IF*A allele was the highest in the Chinese population studied here.

The density of CR1, the C3b/C4b receptor (CD35), on erythrocytes (E) (CR1/E) is genetically determined. However, the broad distribution of CR1/E within a given genotype suggests that other genetic elements might contribute to the regulation of CR1/E. In some pathological conditions, including systemic lupus erythematosus (SLE), AIDS and hemolytic anemia, CR1 deficiency parallels the severity of the disease. When compared to healthy individuals, an accelerated decrease in CR1/E in these patients has been demonstrated, but other mechanisms interfering with CR1 density regulation during erythropoiesis might also contribute. In exceptional circumstances, CR1/E can be dramatically decreased in healthy individuals by the effect of a regulatory gene, In(Lu), that switches off various surface molecules on E, the structure genes of which are located on four different chromosomes, suggesting a transcription regulatory role for In(Lu) gene products. The hypothesis that products of this gene could physiologically regulate the surface density of all these molecules has been tested by determining Lub density on E (Lub/E) using quantitative flow cytometry. Lub antigenic sites were then compared to CR1/E among healthy individuals of the different CR1 density phenotypes, SLE patients with and without CR1 deficiency, and an exceptional SLE patient totally lacking CR1/E and reticulocytes. No quantitative relationship was found between CR1 and Lub expression in either normal or pathological conditions. These data establish that In(Lu) products are not involved in normal or pathological CR1 density regulation.

The RCCX module of the human MHC class III region is comprised of four genes arranged in tandem: RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin X (TNX). Variations in the number and genes of the RCCX modules may lead to genetic and/or autoimmune diseases. Restriction fragment length polymorphism (RFLP) analysis was utilized to determine the RCCX modular variation in patients with juvenile rheumatoid arthritis (JRA). In JRA patient L1, RFLP analysis suggested the presence of a bimodular RCCX structure containing both C4A long and C4B short genes, yet missing the markers for the CYP21A and TNXA genes usually located between the C4A and C4B genes. The 7.5-kb genomic fragment spanning the CYP21-TNX-RP2 genes was cloned and sequenced, revealing that a genetic recombination occurred between TNXA of a bimodular RCCX chromosome and TNXB of a monomodular RCCX chromosome. This recombination results in a new MHC haplotype with a CYP21B gene and a TNXB/TNXA-RP2 recombinant between the two C4 genes. Elucidation of the breakpoint region provides further evidence for the instability of the MHC class III gene region as a result of the RCCX modular variation.

In order to investigate the association of TCR Cbeta and immunoglobulin (Ig) VH polymorphisms with thyroid autoimmune diseases (TAD), we analyzed restriction-endonuclease-generated polymorphisms using T-cell receptor (TCR) Cbeta and VH gene-family-specific probes. We tested genomic DNAs of patients isolated from a large family affected with Graves' disease and Hashimoto's thyroiditis as well as the genomic DNA of unrelated Tunisian controls. Hybridization of BglII-digested DNA with a TCR Cbeta probe revealed two alleles of 9.2 and 10 kb. These Cbeta polymorphisms have already been found in the Caucasian population. However, there was no abnormal distribution of this polymorphism in patients with TAD, compared to related healthy individuals and to unrelated Tunisian controls. Besides, there was a low VH polymorphism in members of the family affected with TAD. Analysis of the Ig gene families revealed no restriction site polymorphism pattern specific for TAD.

At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. In the present study, we compared the effects of the classical chemoattractants FMLP, PAF and LTB4, of the chemokine IL-8 and of TNFalpha, GM-CSF, IFN-gamma and IL-1beta on C5a-induced chemotaxis, degranulation, oxidative burst and expression of adhesion molecules of human neutrophils in vitro. Upon preincubation, TNFalpha as well as GM-CSF dose-dependently inhibited C5a-mediated chemotaxis, but augmented the release of elastase as well as respiratory burst activity. The effects of the two cytokines were accompanied by a downregulation of C5a receptors as determined by Scatchard analysis using (125)I-labeled C5a. Compared on a molar basis, TNFalpha was more effective than GM-CSF. C5a-induced expression of beta(2)-integrins was only moderately influenced by TNFalpha and GM-CSF. C5a itself diminished chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization), whereas heterologous desensitization by FMLP and IL-8 was restricted to C5a-induced degranulation or not observed (PAF, LTB4]. The cytokine effects are likely to be a consequence of altered C5a receptor expression as well as of postreceptor events. In concert with C5a, certain cytokines may shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response.

Interleukin-15 (IL-15) is a recently described cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2. Since IL-15 was shown to stimulate human B-cell proliferation and immunoglobulin secretion, we investigated its effect on human B-cells stimulated with heat-inactivated human immunodeficiency virus type 1 (iHIV-1) in vitro. We observed a dose-dependent elevation of [3H]-thymidine incorporation and immunoglobulin production by B-cells incubated in the presence of iHIV-1. Moreover, IL-15 stimulated HIV-1-driven B-cell proliferation similarly to IL-2. As to immunoglobulin secretion, IL-15 was able to potentiate the stimulatory effect of IL-10. The highest amounts of iHIV caused a decrease in B-cell proliferation and immunoglobulin secretion to baseline levels, even in the presence of cytokines. These findings indicate that during the late stages of AIDS, when monocytes/macrophages become the major site of viral production, IL-15, in concert with other monocyte-derived cytokines, may promote polyclonal B-cell activation and hypergammaglobulinaemia, which are frequently associated with HIV infection.

Levels of plasma alpha1,3-fucosyltransferase (alpha1,3FT) were assayed in 44 patients with schizophrenia and in 50 healthy controls. Significantly reduced enzyme activities were observed in patients (p < 0.05) and 4 unrelated patients were found, for the first time in Japan, to be deficient in the enzyme activity. Two point mutations in the coding region of the FUT6 gene encoding plasma alpha1,3FT that were responsible for the inactivation of the enzyme activity were detected in those patients. Genotyping of the Le gene (FUT3) in these patients demonstrated that 2 of them were also FUT3 deficient and were grouped as Lewis- individuals whereas the rest were Lewis+.