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1.
Sergue? O Fetissov Jarmila Hallman Ida Nilsson Ann-Kari Lefvert Lars Oreland Tomas H?kfelt 《Neuropsychopharmacology》2006,60(8):799-802
BACKGROUND: Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS: Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS: Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS: High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones. 相似文献
2.
Human anti-acetylcholine receptor antibodies use variable gene segments analogous to those used in autoantibodies of various specificities 总被引:2,自引:0,他引:2
Kimberly D. Victor Virginia Pascual Ann Kari Lefvert J. Donald Capra 《Molecular immunology》1992,29(12):1501-1506
The production of autoantibodies to the nicotinic acetylcholine receptor are responsible for many of the neurological symptoms observed in myasthenia gravis. An understanding of the structural organization of the anti-receptor antibodies may help to define the role of these antibodies in the pathogenesis of this disease. The nucleotide sequences of the heavy and light chains of three human monoclonal anti-receptor antibodies isolated from peripheral blood lymphocytes from two patients with myasthenia gravis were analyzed. In addition, the structure of an anti-idiotypic antibody was studied. The VH and VL gene segments used in the anti-receptor antibodies appear to be derived from the same repertoire as gene segments that have been found in other autoantibodies isolated from patients with various autoimmune diseases. The IgM anti-receptor antibodies are direct copies of germline gene segments, while the structures of the IgG anti-receptor antibody and the anti-idiotypic antibody appear to be mutated suggesting that they have undergone antigenic selection. 相似文献
3.
Transforming growth factor-beta (TGF-beta) and tissue transglutaminase expression in the small intestine in children with coeliac disease 总被引:1,自引:0,他引:1
Hansson T Ulfgren AK Lindroos E DannAEus A Dahlbom I Klareskog L 《Scandinavian journal of immunology》2002,56(5):530-537
The production of cytokines from T cells and macrophages is of potential importance for the histological changes apparent in coeliac disease (CoD). Small intestinal biopsy specimens from children with CoD and disease control subjects were investigated for their content of cytokines and tissue transglutaminase (tTG). The transforming growth factor-beta1 (TGF-beta1) expression was increased in the lamina propria of children with villous atrophy. In contrast, TGF-beta3 was expressed at a higher level in the epithelium and the lamina propria of the disease control subjects. The tTG expression was increased in the small intestine of CoD patients as compared with that in subjects. Interleukin-4 (IL-4) was detected in the lamina propria of both CoD patients and controls, and some of the investigated biopsy specimens also showed IL-4 expression in the epithelium. We conclude that children with active CoD could have an altered expression of TGF-beta and tTG in the small intestine and that a disturbed regulation of TGF-beta may be of importance in the immune pathogenesis of CoD. 相似文献
4.
Characterization of anti-acetylcholine receptor antibody activity in patients with anti-mitochondrial antibodies 总被引:1,自引:0,他引:1
Antibodies binding to the acetylcholine receptor of human skeletal muscle were found in patients with different kinds of anti-mitochondrial antibodies. In patients with primary biliary cirrhosis (PBC), the antibody activity was found in monomeric and pentameric IgM as well as in IgG, whereas patients with other kinds of anti-mitochondrial antibodies had anti-receptor antibodies of predominantly IgG class. Mice transfused with immunoglobulins from patients with PBC showed a reduction of skeletal muscle receptors comparable to that found in mice who had received immunoglobulins from myasthenia gravis (MG) patients. The antibody affinity was of the same order of magnitude in MG and PBC but antibodies with multiple affinities were more common in PBC. In PBC, the anti-receptor antibody associated idiotype repertoire was markedly different from that found in MG. 相似文献
5.
6.
The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients. 相似文献
7.
Polymorphisms at - 174 and in the 3' flanking region of interleukin-6 (IL-6) gene in patients with myasthenia gravis 总被引:1,自引:0,他引:1
Huang D Zheng C Giscombe R Matell G Pirskanen R Lefvert AK 《Journal of neuroimmunology》1999,101(2):197-200
We examined the bi-allelic polymorphism at - 174 in the promoter region and the polymorphism in the 3' flanking AT rich region of the interleukin-6 (IL-6) gene in Swedish patients with myasthenia gravis (MG) and ethnically matched healthy individuals. There was no association between the polymorphisms and the disease. There was no relation of the polymorphisms to the clinical variables, the thymic histopathologies, the level of serum acetylcholine receptor antibodies or the concentrations of IgG and its subclasses. Our data yield no evidence for the IL-6 gene contributing to the disease susceptibility. 相似文献
8.
OBJECTIVE: To analyze the association of Wegener's granulomatosis (WG) with 2 single nucleotide polymorphisms (SNP), a +49 A/G polymorphism in coding sequence (CDS) 1 and a C/T base exchange in the promoter region at position -318. METHODS: Restriction enzyme digestion of PCR amplified genomic DNA was used to analyze the CTLA-4 SNP in 32 patients with WG and 100-122 ethnically matched healthy controls. RESULTS: Patients were more often heterozygous for C/T in the promoter region (31% of the patients vs 14% of controls; p < 0.05). Homozygosity for C was less frequent in patients (69% of patients vs 86% of controls; p < 0.05). There was no association with the A/G SNP in CDS 1. There was a linkage disequilibrium between allele A of CDS 1 and the shortest allele, 86 bp, in the (AT)n of the 3' untranslated region in controls but not in patients. CONCLUSION: The CTLA-4 SNP in the promoter region at position -318 is associated with WG. The loss of linkage disequilibrium between allele A of CDS 1 and the short 86 bp in the (AT)n in patients indicates that the promoter SNP and the (AT)n polymorphism are independent genetic risk factors. 相似文献
9.
Susanne Bergenbrant Qing Yi Anders Österborg Magnus Björkholm Eva Ösby Hkan Mellstedt Ann Kari Lefvert Göran Holm 《British journal of haematology》1995,92(4):840-846
Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19+ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established. 相似文献
10.
Xu B Arlehag L Rantapää-Dahlquist SB Lefvert AK 《Scandinavian journal of rheumatology》2004,33(6):395-398
The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein-coupled receptors and is present on skeletal and cardiac muscle cells and on lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population and the distributions of single-nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164 are changed in asthma, obesity, and hypertension and in the autoimmune disease myasthenia gravis. An involvement of the beta2-AR has also been suggested in human rheumatoid arthritis (RA) and its animal model. We describe here an increased prevalence of the alleles Arg16 and Gln27 and a lower prevalence of homozygosis for Gly16 and Glu27 in patients with RA. Patients having the genotype combination GlyGly16-GlnGlu27 had higher levels of rheumatoid factor (RF) and a more active disease than other patients. Patients having the genotype Arg16-Gln27+ had higher levels of RF when compared to those having Arg16+Gln27+, and patients who were carriers of Gln27 had a more active disease than non-carriers of Gln27. Our results show an association of beta2-AR SNPs with RA in a population from the northern part of Sweden. Our study also confirms the strong linkage disequilibrium of genotypes at amino acid positions 16 and 27. 相似文献