A novel missense mutation 15747 T>C in the mitochondrial cytochrome b gene.
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Amino Acid Substitution↗
Biomedical subjects
A Núñez-Roldán
Publications and source records attributed to A Núñez-Roldán.
Lack of association of MICA transmembrane region polymorphism and Behçet's disease in Spain.
We have analyzed the distribution of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane alleles among 58 Spanish patients with Behçet's disease (BD) and in 194 ethnically matched healthy controls. The study included the characterization of A4, A5, A5.1, A6 "new" and "old" and A9 MICA-TM alleles using polymerase chain reaction. As previously reported, the serological B51 specificity was increased among this BD patient group (36.25% vs. 19.6% in controls; P=0.009; OR=2.33). The MICA-TM alleles A6 ("new" and "old"), in linkage disequilibrium with HLA-B51 and HLA-B14 respectively, were only slightly increased among patients (70.7% vs. 61.3% in controls; P=NS). We conclude that, in contrast to previous finding reporting a strong association of MICA-TM genes and Behçet disease in Japanese patients, in our population HLA-B51 is more closely associated to Behçet susceptibility than MICA-TM genes. Finally, our data show that in Spain, as occurs in other populations, some MICA-TM alleles exhibit strong linkage disequilibrium with certain alleles of the HLA-B locus.
Behcet Syndrome↗
Autoimmune deafness is not related to hyperreactivity to type II collagen.
The pathogenic role of anti-type II collagen was analysed in a variety of hearing losses, in age-matched controls and in different autoimmune diseases. The immune reactivity of peripheral blood lymphocytes to type II collagen was studied by the degree of proliferation measured as the incorporation of bromodeoxyuridine in cultured lymphocytes. The anti-type II collagen antibodies showed a very low incidence in the hearing loss group. Lymphocytes of otosclerosis, Meniere's disease and other sensorineural deafness patients proliferated in response to concanavalin A and to type II collagen to a lower extent than peripheral blood lymphocytes from healthy controls. Nonetheless, these differences were not statistically significant. The immune hyperreactivity to type II collagen cannot explain the autoimmune mechanism of hearing losses. Humoral and cellular hyperreactivities to inner ear proteins different from type II collagen, could explain the autoimmune mechanism of deafness.
Adolescent↗
Detection of anti-PL-12 autoantibodies by ELISA using a recombinant antigen; study of the immunoreactive region.
Autoantibodies to aminoacyl-tRNA synthetases are highly associated with myositis and detection is important in clinical diagnosis; however, current methods of screening limit its clinical utility. In the present study, alanyl-tRNA synthetase (PL-12) recombinant protein was obtained by immunological screening of a HeLa expression library and used in an ELISA with 22 anti-PL-12 sera, 200 autoimmune sera negative for PL-12 and 100 healthy individual sera. Sensitivity of the method was 95% (21/22) and specificity 100%. Mapping of the immunoreactive region was carried out using three anti-PL-12 sera and different recombinant protein-derived peptides. Results show that the same conformational epitope located within amino acids 730-951 of the PL-12 antigen outside the catalytic region was recognized by the three anti-PL-12 sera tested. We conclude that ELISA using recombinant protein is an effective and useful method for routine screening for anti-PL-12 autoantibodies.
Alanine-tRNA Ligase↗
The frequent expansion of a subpopulation of B cells that express RF-associated cross-reactive idiotypes: evidence from analysis of a panel autoreactive monoclonal antibodies.
Preferential expression of VH gene segments is evident within the adult human primary B-cell repertoire. The repertoire may be influenced by genetic factors, e.g. VH gene segment polymorphisms, or in a temporal manner due to the exposure to environmental antigens. The molecular characteristics of 15 autoreactive human monoclonal antibodies (MoAbs) are reported. All antibodies were of the IgM isotype, and 12 of the 15 were polyreactive and included rheumatoid factor type specificity, i.e. reactivity with IgG. Nine of the 15 MoAbs are products of VH3 gene segments, as evidenced by staphylococcal protein A binding; four of these express the cross-reactive idiotype recognized by the mouse MoAb 3H7 and are thus products of the VH26 gene segment. One of the five remaining VH3 gene products expresses the cross-reactive idiotypes recognized by the mouse MoAbs B6 and D12. V-gene family usage, determined by polymerase chain reaction (PCR) amplification of cDNA and further hybridization with family-specific oligonucleotide probes, confirmed the cross-reactive idiotype studies and showed that only VH3-gene-encoded proteins bound staphylococcal protein A. Five of the six non-VH3 gene segment products express the cross-reactive idiotype recognized by the mouse MoAb LC1 and could be assumed to be products of the VH4.21 gene segment; however, one human MoAb is shown to be the product of a VH2 gene segment. This is interesting because it turns LC1 from being an anti-cross-reactive idiotype antibody into an anticlan reagent.
Animals↗
HLA-Cw*1602: a new susceptibility marker of Behçet's disease in southern Spain.
Genotyping of the HLA-C locus by PCR-SSP in Behçet's disease patients from southern Spain reveals a statistically significant association with Cw*1602 (OR 20.15, corrected p < 0.05). This is an uncommon allele absent from the healthy control group, which seems to confer higher relative risk than B51 in this study (OR 1.85). Stratified frequencies do not show statistically significant differences but suggest that the Cw*1602-B51 haplotype could be the main HLA marker of Behçet's disease in the analyzed population.
Alleles↗
Association of HLA-B51 subtypes and Behçet's disease in Spain.
We have studied the distribution of the different HLA-B51* alleles among patients with Behçet's disease (BD) and ethnically matched healthy controls in a Spanish population. The serological B51 specificity was increased in BD patients (37.5% versus 15.5% in controls). Among the B51-associated alleles, the frequencies of B*5101 (32%) and 5108 (5.5%) were increased in BD patients with respect to the control frequencies (13% and 1.2% respectively). The fact that different HLA-B51 subtypes are associated with BD could suggest that common motifs shared by HLA-B51-related alleles are involved in the susceptibility to BD or, in the light of recent studies, that a mutation causing the susceptibility to BD occurred in the B*5101 haplotype, close to HLA-B gene, before the divergence of B*5108 from the B*5101 allele.
Alleles↗
Distribution of HLA class II alleles among Spanish patients with pemphigus vulgaris.
Twenty-six unrelated Spanish Caucasian individuals affected by pemphigus vulgaris (PV) were HLA typed and frequencies compared with those of 200 ethnically matched healthy controls. Twenty-three out of 26 patients were HLA-DR4. The frequency of HLA-DR14 was also increased (31%; controls: 4%). Of the 23 patients positive for HLA-DR4, 21 carried the DRB1*0402 allele. Therefore, the frequency of HLA-DRB1*0402 among patients was 81% (4% in controls; P=4.7x10(-27), OR=100.8). Interestingly, HLA-DR13, a frequent HLA-DR specificity in the Spanish general population (27%), was absent among the PV patients (P=0.009; Pc=0.1; OR=0.05). Taking together these data, we can conclude that, in the Spanish population, PV is preferentially and strongly associated with HLA-DRB1*0402, whereas DRB1*13 seems to confer a protective effect in our population.
Alleles↗
Lack of suppressive antibody activity in sera from patients with active-phase autoimmune diseases.
To investigate the presence of a suppressive antibody activity in sera from patients with autoimmune diseases, the IgG autoreactivity in whole serum was compared to that of the IgG fraction purified by affinity chromatography on protein G-sepharose. Competitive inhibition assays on the binding to histone, dsDNA, RNP and thyroglobulin of the purified IgG fraction by the autologous IgM present in serum without IgG and depleted of <100 kD components (named IgM fraction) were also performed. The IgG reactivity to the autoantigens tested was considerably increased in the IgG fraction than in the whole serum drawn from a healthy control and from three SLE patients in an inactive-phase of disease. Addition of the IgM fraction to the autologous purified IgG resulted in a dose-dependent inhibition of IgG binding to the autoantigens tested. However, no differences were observed between the autoreactivity of the IgG in whole serum and that of the purified IgG fraction from active-phase SLE patients, or from two patients with autoimmune thyroiditis, and the autologous IgM fractions did not inhibit significantly binding to the autoantigens under study of the purified IgG fraction. Our findings support the concept that the IgG autoreactivity in physiological conditions is regulated by idiotypic interactions between IgG and IgM, and suggest that this regulation is broken in the active phase of autoimmune diseases and that clinical remission from SLE could be associated with the restoration of this control mechanism. Additionally, qualitative differences, such as polyreactivity or change of idiotype in the autoreactive IgG fraction from active-phase disease might contribute to escape of regulation.
Autoantibodies↗
Human polyreactive IgM monoclonal antibodies with blocking activity against self-reactive IgG.
Natural IgM antibodies have been found to be involved in the control of IgG reactivity in normal serum. The authors investigated the blocking activity of four human IgM monoclonal antibodies (BY-2, BY-7, BY-10 and IRM-7) derived from B-cells from blood samples of three renal dialysis patients, which had shown multispecific properties similar to those observed for natural polyreactive autoantibodies. To achieve this, competitive inhibition assays were performed with these MoAbs on the binding of IgG purified from a healthy control, three patients with SLE, and two patients with autoimmune thyroiditis, to histone, dsDNA, RNP and thyroglobulin. MoAbs inhibited binding of self-reactive IgG to histone and dsDNA, but not to thyroglobulin or RNP, of natural and active or inactive phase disease-associated autoreactive IgG. The inhibitory effect of the MoAbs was mediated by V-region dependent interactions with autoreactive IgG, as shown by the ability of these MoAbs to block the binding of F(ab')2 fragments of autoreactive IgG to antigens (histone and dsDNA). The blocking of autoantibody activity was dose-dependent with maximal inhibition occurring at a specific molar ratio between the patient's IgG and a given MoAb. In contrast, MoAbs did not inhibit binding of IgG alloantibodies present in the sera of four polytransfused renal dialysis patients to target antigens on the surface of different cells. These results support the concept of a functional idiotypic network regulating autoimmune responses, and suggest that the IgM MoAbs under study may be natural polyreactive antibodies belonging to the physiological network of autoantibodies with highly connected V-regions, capable of binding and functionally neutralizing V-regions of natural and pathologic autoantibodies.
Antibodies, Anti-Idiotypic↗
Human lymphocytotoxic monoclonal autoantibodies from a highly sensitized renal dialysis patient.
A panel of 5 human monoclonal autolymphocytotoxic antibodies (IRM-3, IRM-4, IRM-7, IRM-8, and IRM-10) of the IgM class was established from a highly sensitized renal dialysis patient (IRM), by the generation of mouse-human heterohybridomas. This panel was screened for reactivity against foreign and autoantigens by ELISA, and for reactivity against different tissue sections and HEp-2 slide preparations by indirect immunofluorescence. Cytotoxicity screening of heterohybridoma supernatants gave broad panel reactivity profiles, being cytotoxic against B cells from patient IRM and also against most B cells tested and less reactive with chronic lymphocytic leukemia B cells; T cells were the least sensitive target. Immunoblotting showed that monoclonal IRM displayed some heterogeneity in their binding profiles, although all of them recognized a cellular structure of 26 kDa. None of the heterohybridoma cell lines exhibited cytoplasmic nor surface staining with an anti-CD5 mAb. Results obtained showed that all the autolymphocytotoxic mAbs generated were also able to react against certain nuclear and cytoplasmic self-structures as well as foreign compounds. Monoclonal antibody IRM-7 and, to a lesser degree, IRM-10 exhibited multispecific properties similar to those observed for polyreactive or natural antibodies.
Antibodies, Monoclonal↗
Caucasian patients with rheumatoid factor-positive RA.
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
TAP polymorphism in patients with Behçet's disease.
OBJECTIVE: To determine if susceptibility to Behçet's disease (BD) is associated with polymorphism of HLA-DRB1, HLA-DQB1, DQB1, and TAP1 and TAP2 genes. METHODS: Fifty eight Spanish BD patients and 116 ethnically matched unrelated healthy subjects were typed at the HLA-DRB1 and HLA-DQB1 loci using polymerase chain reaction/sequence specific oligotyping (PCR/SSO). TAP1 and TAP2 alleles were assigned using amplification refractory mutation system-PCR. RESULTS: TAP1C was absent in BD patients, but was found in 12.1% of control subjects (pcorr < 0.05; relative risk = 0.06). Additionally, a linkage disequilibrium between HLA-DQB1*0501 and TAP2B was observed in BD patients (delta = 0.095, pcorr < 0.02), but not in the control group (delta = -0.0031, p > 0.05). CONCLUSIONS: The complete absence of TAP1C alleles in BD patients may indicate that TAP1 polymorphism is not without some significance in the development of BD. Furthermore, the existence of a linkage disequilibrium between HLA-DQB1*0501 and TAP2B in our patients suggests that the gene conferring susceptibility for BD is inherited as an extended haplotype in the population studied.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Application of the MAILA technique to the study of human anti-HLA monoclonal antibody specificity.
The monoclonal antibody-specific immobilization of lymphocyte antigens (MAILA) assay was developed to detect antibodies present in human alloantisera against antigens of different major histocompatibility complex loci, particularly of class II specificity. The MAILA assay has been used in our laboratory to the determination of the type of HLA molecule recognized by human monoclonal antibodies 91C2 (anti-A2 + 28), 34F11 (anti-DQ1), and 2A2 (anti-DQ1 + 4 + short DQ7), using well characterized monomorphic as well as polymorphic murine monoclonals for the specific immobilization of HLA molecules. Results obtained show that the MAILA assay is also a valuable tool for the determination of specific human MHC locus products recognized by human monoclonal antibodies.
Animals↗
Psychological problems in the family members of gravely traumatised patients admitted into an intensive care unit.
The aim of these studies was the analysis of the psychological repercussions on the closest members of families of 76 gravely traumatised patients admitted into the Intensive Care Unit (ICU) of the Hospital Universitario de Rehabilitación y Traumatología "Virgen del Rocio", Sevilla (Spain). An investigation based on social information and the Clinical Analysis Questionnaire was used. The sample of family members was composed of 42 women and 34 men, with an average age of 41.3 years (SD +/- 12.8). Results showed that (a) more than 50% of the family members of gravely traumatised patients admitted into an ICU showed symptoms of depression, (b) the women scored more points in hypochondria, suicidal depression, anxious depression, low-energy depression, guilt-resentment, apathy-withdrawal, paranoia, schizophrenia, psychasthenia and psychological disadjustment, and (c) in general terms, the psychological characteristics of the families were far from the norm of the control group.
Adult↗
[DIDMOAD syndrome. Study of 3 families with 5 new cases. Differentiation from classic insulin-dependent diabetes mellitus].
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Adolescent↗
[Acquired myasthenia gravis and HLA system].
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Adolescent↗