Fisher's syndrome, anti-GQ1b antibody, and HLA-B39 antigen.
Explore the source record for details and available documents.
Autoantibodies↗
SEARCH · PubMed Health
Results for “HLA-B39 Antigen”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Peptide motifs of HLA-B38 and B39 molecules.
Explore the source record for details and available documents.
Amino Acid Sequence↗
A cytotoxic human hybridoma monoclonal antibody (TrJ5) specific for HLA-B38(16) and -B39(16).
We have generated a cytotoxic IgM lambda human hybridoma mAb (TrJ5), that is specific for HLA-B38(16) and -B39(16). Among a panel of 42 HLA-defined cell lines, TrJ5 killed all five B38-positive and both B16-positive cell lines, as well as the single B39-positive cell line, but not any cell lines lacking these antigens. It could be ruled out that the TrJ5 epitope is located on the alpha 1 domain because TrJ5 did not react with cells bearing HLA-B14, the alpha 1 domain of which is identical to alpha 1 of B39. In the alpha 2 domain of B38 and B39, a unique threonine residue at position 158 (Thr-158) is not shared by any of 29 other HLA-B alleles. This suggests that Thr-158 of the alpha 2-domain helix is critical for the TrJ5 epitope.
Antibodies, Monoclonal↗
Identification of the gene encoding a novel HLA-B39 subtype. Two amino acid substitutions on the beta-sheet out of the peptide-binding floor form a novel serological epitope.
Serological analysis suggests the existence of a novel HLA-B39 subtype (HLA-B39N) in the Japanese population. To identify this novel allele, a gene encoding HLA-B39N was cloned and the exons were sequenced. A gene encoding HLA-B39N (B*3904) and B*39011 differs by two nucleotide substitutions at codons 11 and 12 whereas B*3904 and B*39013 differ by three nucleotide substitutions at codons 11, 12, and 312. One nucleotide difference at codon 11 produces a change from serine in B*3901 to alanine in B*3904 whereas another difference at codon 12 changes valine in B*3901 to methionine in B*3904. The residues 11 and 12 are located on the beta-sheet out of the peptide-binding floor and are completely buried in the molecule. These results suggest that the substitutions at these residues alter the conformation of other residues forming epitopes of alloantibodies. Analysis of HLA-B*3901 genes in the Japanese population showed that both B*39011 and B*39013 were observed in the Japanese population. The present study suggests that B*3904 may have evolved from B*39011 rather than B*39013.
Amino Acid Sequence↗
DNA typing of HLA-B gene in Takayasu's arteritis.
Sixty-four patients with Takayasu's arteritis and 156 healthy individuals in the Japanese population were examined for HLA-B specificity at the DNA level by DNA typing using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe (SSOP) analysis and by subsequent sequencing analysis. The frequency of epitope combination group-B52 (EC-B52) corresponding precisely to HLA-B52 specificity and that of EC-B39.2 which is a newly-identified subtype of HLA-B39 specificity were increased in the patient group. These two disease-associated HLA-B alleles share an epitope composed of 63Glu and 67Ser. Because two HLA-B alleles, HLA-B51 and B39.1, which are similar but different at the epitope from HLA-B52 and B39.2, respectively, are not associated with Takayasu arteritis, 63Glu and 67Ser are supposed to be involved in the pathogenesis.
Alleles↗
A comprehensive approach for typing the alleles of the HLA-B locus by automated sequencing.
We describe an approach for typing alleles of the HLA-B locus by using automated sequencing technology. The exon 2 and exon 3 nucleotide sequence of each allele is determined directly from genomic DNA in two steps. In the first step, HLA-B exon 2, intron 2 and exon 3 sequences are amplified with one or two primer pairs out of a panel of 5 primer pairs that describe all known HLA-B alleles. In the second step, templates are sequenced in 5' and 3' orientations in a PCR assay that utilizes Taq polymerase to incorporate fluorescent dye-labeled nucleotides into each new strand synthesized. Gel electrophoresis of the labeled products is performed in an automated DNA sequencer. The derived sequences are aligned against reference sequences and each nucleotide position is evaluated for homology to consensus sequence. Using this strategy, the HLA-B allele sequence is directly ascertained with precision and efficiency. The automated sequencing strategy can be readily applied in the clinical laboratory as a practical tool for high resolution typing of HLA-B alleles.
Alleles↗
HLA-B39 and the axial type of psoriatic arthritis.
The frequency distribution of HLA-B38 and HLA-B39 was studied in a group of 50 unrelated psoriatic arthritis patients. A high increase of HLA-B39 was noted in the subgroup with axial arthropathy. All B39 positive patients presented with spondylitis and/or sacroiliitis. The hypothesis is formulated that HLA-B39 may discriminate a genetic subset of psoriatic arthritis characterized by a particular susceptibility to develop axial involvement.
Arthritis↗
The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Multivariate relative risk model.
OBJECTIVE: To identify HLA markers for the development of severe disease in psoriatic arthritis (PsA). METHODS: Patients with PsA who were followed up prospectively over a 14-year period were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6-month intervals according to a standard protocol, which also included serologic HLA typing for class I and II antigens. Progression of damage was defined as transition into higher damage states, defined by the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. RESULTS: Univariate analysis revealed that the HLA antigens B27, B39, and DQw3 were associated with disease progression, while HLA-DR7 was "protective." The best multivariate model identified the HLA antigens B27, when DR7 was present, and DQw3, when DR7 was not present, as predicting disease progression across all transitions, while HLA-B39 was associated with progression in early disease. The addition of these HLA indicators to a model containing clinical variables resulted in a significant improvement in fit. CONCLUSION: The HLA antigens associated with PsA, B27 and B39, are risk factors for disease progression, as is the HLA class II antigen DQw3. In combination with clinical measures of disease, these HLA variables are the dominant predictors of progression.
Adolescent↗
Association of HLA-B39 with HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. Evidence for a role of the peptide-anchoring B pocket.
OBJECTIVE: To investigate the characteristics of HLA-B27 that render susceptibility to seronegative spondylarthropathies. METHODS: Serologic HLA class I typing of Japanese patients with ankylosing spondylitis (AS), juvenile rheumatoid arthritis (JRA), and healthy controls, was performed. HLA-B39 subtypes were determined by polymerase chain reaction-sequence-specific oligohybridization. RESULTS: HLA-B27 was present in 40 of 48 patients with AS (83%), and in only 1 of 210 healthy controls (0.5%). Three of 8 patients (37.5%) who were negative for HLA-B27 were positive for HLA-B39, which was significantly higher compared with the HLA-B27-negative controls (6.2%; P = 0.01). Significant association with HLA-B39 was also noted in the JRA patients (16.7%; P < 0.01), especially in those patients with pauciarticular-onset disease (33.3%; P < 0.01). Ten of 13 HLA-B39-positive patients had subtype B*3901 and 3 had B*3902. CONCLUSION: Because HLA-B27 and HLA-B39 share Glu at position 45 and Cys at position 67, both of which constitute components of the peptide-anchoring B pocket, and because they possess similar peptide-ligand motifs, our results may support either the role of the peptides presented by class I antigens or the importance of Cys at position 67, in the development of spondylarthropathies and pauciarticular-onset JRA.
Arthritis, Juvenile↗
Identification of the Novel HLA-B*39:188 Allele by Next-Generation Sequencing.
HLA-B*39:188 differs from HLA-B*39:15 by a single nucleotide substitution at position 1043 C>T.
Humans↗
The Novel HLA-B*39:194Q Allele Identified in an Individual From West Bengal, India Using Sequence-Based Typing.
HLA-B*39:194Q differs from HLA-B*39:01:01:03 by a single nucleotide substitution in codon -24.
Humans↗
The cervical spine in patients with psoriatic arthritis: a clinical, radiological and immunogenetic study.
The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.
Arthritis, Psoriatic↗
HLA-B27 screening by flow cytometry.
A flow cytometric assay for lymphocyte HLA-B27 expression using a two-color direct immunofluorescent assay was compared to traditional microlymphocytotoxicity testing on 209 clinical samples. For the flow cytometric assay, whole blood was mixed with a monoclonal anti-B27 conjugated to fluorescein-isothiocyanate (FITC) and anti-CD3 conjugated to phycoerythrin (PE). The samples were analyzed with flow cytometry by gating on CD3 positive events and anti-B27 staining intensity was evaluated as median channel fluorescence of the histogram peak. The median channel fluorescence was least with B27 negative and B7 negative samples (84 +/- 17), intermediate with samples that were B27 negative but B7 positive (118 +/- 13), and greatest with samples that were B27 positive (155 +/- 13). In addition to cross-reactivity with the B7 antigen (n = 38), the monoclonal anti-B27 cross-reacted with HLA-B37 positive samples (n = 3) and HLA-B39 positive samples (n = 3). Using a median channel fluorescence cutoff of 136, 39 of the 40 B27 positive samples gave positive results in the flow cytometric assay for a sensitivity of 97.6%. The specificity was 95.9% with 7 false positives of 169 B27 negative samples. The flow cytometric HLA-B27 assay is a convenient, useful screening test. For greatest specificity, samples positive by flow cytometry should be confirmed by conventional microlymphocytotoxicity or by use of other monoclonal antibodies directed against B27.
Flow Cytometry↗
HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles.
Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles.
Alleles↗
Differential regulation of HLA class I genes by interferon.
Allele-specific differences in the regulation of HLA class I genes by type I interferon (IFN) were observed after transfection of eight HLA-B, -A, or -C genes into mouse L cells. HLA-B7 and -Bw64 gene expression was significantly more inducible by type I IFN than the genes coding for HLA-B27, HLA-B51, HLA-B38, HLA-B39, HLA-Cw3, and HLA-A2 antigens. Modification of the 5' end of HLA-B7 and HLA-B27 genes revealed the presence of enhancer sequences responding to IFN treatment in the 5' untranslated region of HLA-B7, but not of HLA-B27 and suggested further, independently acting enhancer elements downstream of the transcription initiation site. Comparison of 5' enhancer region sequences in correlation with type I IFN inducibility of the different HLA class I alleles indicated that the exchange of only two nucleotides in the interferon response sequence (IRS) or enhancer A region of HLA-B7 or -Bw64 could account for nonregulated promoters in all other HLA-A, -B, or -C alleles analyzed. Thus, type I IFN stimulation of HLA class I genes in mouse L cells appears to predominantly operate in most alleles by a mechanism targeted to enhancer sequences downstream of the gene's transcription initiation site.
Alleles↗
Sharing of MHC haplotypes among apparently unrelated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
From the study of HLA, complement, and glyoxalase I alleles in 82 Venezuelan individuals belonging to 19 families of mixed ethnic origin having 20 affected newborns with salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, a total of 38 disease haplotypes and 53 nondisease haplotypes were found. Of the pathological haplotypes 47% were found to share the HLA-B39 or -Bw62 specificities, 55% of them in combination with the BFS, C2C, C4A4, C4B2 (SC42) complotype. The frequencies of HLA-B39 and -Bw62 among the affected haplotypes were 29 and 18% as compared with 6 and 0% among the nondisease haplotypes of the same families. Statistical associations (P less than 0.01) with salt-wasting adrenal hyperplasia were found with the SC42 complotype and with the combination SC42, HLA-B39. These results are markedly different from those reported in the literature which show an "association" at the population level among many Caucasoid samples of HLA-Bw47 and the extended haplotype (HLA-Bw47, DR7,FC91,0) with the salt-wasting form of the disease. Furthermore, four of the unrelated patients reported here were homozygous for all the major histocompatibility complex loci tested, while three others were homozygous for at least two HLA loci. Analysis of the geographical origin of the grandparents indicated clustering of the deficiency carrier HLA haplotypes. This observation, together with the fact that there is an excess of homozygotes among the patients in Venezuela, strongly suggests that salt-wasting 21-OH deficiency congenital adrenal hyperplasia is mostly the result of a founder effect of relatively hyperplasia is mostly the result of a founder effect identity by descent of a few abnormal alleles at the 21-OHB locus in most cases. The mutation marked by HLA-Bw47 was not observed in this population.
Adrenal Hyperplasia, Congenital↗
Genetic susceptibility to early onset pauciarticular juvenile chronic arthritis: a study of HLA and complement markers in 158 British patients.
To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, Bf*S, C4A*4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.
Age Factors↗
Pathogenesis and treatment of myasthenia gravis.
Lymphocyte subsets and viruses were examined in the thymuses and thymomas of patients with myasthenia gravis (MG). Most of the lymphocytes were considered to be from cortical thymocytes since they were positive for OKT4, 6, 8 and 10. Retrovirus-like particles were detected in the thymuses and thymomas from patients with MG. These data suggest contributions of lymphocytes and viruses in the pathogenesis of MG. HLA antigen frequencies in 49 patients with MG were studied to investigate a genetic background. Although the association of HLA-B8, DR3, DRw52 haplotype with Caucasian MG has been reported, Japanese MG seems to be associated with a different haplotype, HLA-B39, Cw7, DRw8. To achieve a better understanding of the association of HLA with MG, analysis of restriction fragment length polymorphism (RFLP) of DNA from MG patients was performed. When DQ beta cDNA probe was used, the increased frequency of PstI 12 kilobase fragment was observed in HLA-DR2 positive patients compared to healthy DR2 positives. For treating MG patients, we have been utilizing low-dose prednisolone (PSL) or high-dose gammaglobulin. Our results so far indicate that low-dose PSL seems to be as effective as high-dose PSL therapy, however, we could not observe any favorable effect of high-dose gammaglobulin therapy on MG.
Autoimmune Diseases↗