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O Olerup

Publications and source records attributed to O Olerup.

At least 37 records · Page 2Linked to original sources
PubMed1997

A novel DRB1*13 allele (DRB1*1327) on a DR17, DQ2 haplotype with a DRB1*0301 sequence motif in the 2nd hyperpolymorphic region.

In a sample from a Netherlands Caucasian, we found a new DRB1*13 allele (DRB1*1327). The nucleotide sequence of the second exon of the novel allele was identical to DRB1*1301 except for a single productive base substitution changing codon 26 from TTC to TAC, encoding phenylalanine and tyrosine, respectively. The new allele shares sequence with DRB1*03011 from codons 5 to 66. The haplotype carrying the new allele was, from known linkage disequilibria, deduced to be DRB1*1327, DRB3*0101, DQA1*05011, DQB1*0201, i.e. similar to the DR17, DQ2 haplotype, which suggests that the DRB1*1327 allele has arisen by a double recombination event between a DR13 donor haplotype and a DR17, DQ2 recipient haplotype.

Alleles↗
PubMed1997

DQB1*0202 and the new DQB1*0203 allele: a fourth pair of DQB1 alleles differing only at codon 57.

Amino acid 57 of DQ beta chains is of functional importance as it influences peptide binding, is part of B and T cell epitopes, and is associated with susceptibility and resistance to insulin-dependent diabetes mellitus and humoral immunodeficiencies. Polymorphism of codon 57 is conserved in primates and in HLA class II B genes implying that balancing selection operates on this residue. Previously, three DQB1 allele pairs have been described, that only differ at residue 57. In an African-American Black individual with the HLA phenotype A23.30;B58,63;Cw6;DR18,12;DR52;DQ5,2, we found a fourth example of this dimorphism: the new DQB1*0203 allele, that was identical to DQB1*0202 except for codon 57, which encodes aspartic acid and alanine respectively in the two alleles. The class II haplotype carrying the new allele was deduced to be DRB1*0302,DRB3*0101,DQA1*05011,DQB1*0203.

Alleles↗
PubMed1997

HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis.

Although most patients with sarcoidosis have a good prognosis, a significant proportion runs a more severe and prolonged disease course. There is no marker to distinguish these subpopulations of patients, however. To investigate the relationship between HLA haplotype and clinical course, 122 Scandinavian patients with sarcoidosis were genomically typed for HLA-DR, -DQA1 and -DQB1 alleles using PCR amplification with sequence-specific primers. Control subjects were 250 healthy Swedish volunteers. Patients were carefully clinically monitored for up to 10 yr. We found that HLA-DR17(3) was overrepresented among sarcoidosis patients (33%) compared with control subjects (17%, p < 0.001). Ninety-one patients were followed for more than 2 yr and classified into chronic or nonchronic patients, according to disease outcome. Among the 34 patients with a nonchronic form of sarcoidosis, 65% were DR17(3)-positive (p < 10(-5) versus control subjects). On the other hand, DR14(6) and DR15(2) were significantly associated with chronic disease. Even in patients with clinical manifestations that are normally associated with good prognosis, HLA typing enabled a subgrouping into two categories with significantly different clinical courses. Therefore, HLA class II typing is a valuable tool in predicting the outcome of the disease in Scandinavian sarcoidosis patients.

Adult↗
PubMed1997

Linkage analysis of HLA class II genes in Swedish multiplex families with multiple sclerosis.

We assessed the influence of human leukocyte antigen (HLA) class II as susceptibility genes in multiple sclerosis (MS) by linkage analysis. Other research groups, who have shown negative results in studies on affected sibling pairs, have questioned the influence of the HLA class II genes, although they confirmed the association of the DR15,DQ6,Dw2 haplotype to MS. In this report, we find a significant lod score (>3) when using a 2-point linkage analysis of 49 small Swedish nuclear MS families with at least two affected family members, typed for HLA class II alleles by PCR amplification with sequence-specific primers. We obtained maximum lod scores when we used dominant or intermediate models with low penetrance. We found that the positive effect on the total lod score was not confined to those families carrying the presumed susceptibility HLA-haplotype Dw2. This observation supports the notion of a functional role of the HLA class II molecules themselves in MS. In addition, we observed significant transmission distortion and an intrafamilial association of the MS-associated class II haplotype HLA-Dw2. These results indicate that the HLA class II genes are of clear importance for MS in the studied population.

Disease Susceptibility↗
PubMed1997

Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis.

Patients with extrinsic allergic alveolitis (EAA) have accumulations of T-lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been implicated in the pathogenesis of EAA. The objective of the present study was to analyse the T-cell receptor (TCR) V alpha and V beta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBLs) before and after treatment. Twelve patients with clinical signs of extrinsic allergic alveolitis were studied at disease onset, and nine of the 12 were also studied after treatment and clinical recovery. Lung cells, obtained by bronchoalveolar lavage (BAL), and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V monoclonal antibodies. The changes in TCR V gene usage were most pronounced in BAL CD8+ cells, as compared to the BAL CD4+, PBL CD8+ and PBL CD4+ subsets. At disease onset, 10 of the 12 patients had lung restricted expansions of CD8+ T-cells using a particular V alpha or V beta gene segment, and 8 of the 12 patients had CD8+ T-cell expansions in PBL. For the patients in whom a follow-up was possible, a majority of the expansions in the lungs were normalized, whereas most of the expansions in PBL remained. An over-representation of human leucocyte antigen (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An increased selected T-cell receptor V gene usage may follow specific interactions between T-cells and antigens. In extrinsic allergic alveolitis, we determined that such expansions occur most frequently in the lung CD8+ T-cells. Since most expansions of lung CD8+ T-cells normalized with clinical improvement, these are further implicated in the pathogenesis of extrinsic allergic alveolitis.

Acute Disease↗
PubMed1996

HLA-DPA1 typing by PCR amplification with sequence-specific primers (PCR-SSP) and distribution of DPA1 alleles in Caucasian, African and Oriental populations.

In the present study PCR primers were designed for detecting all known DPA1 variability, i.e., the presently recognized six DPA1 alleles 0103 to 0401, and also for separation of the four DPA1*02 alleles, by PCR amplification with sequence-specific primers (PCR-SSP). For each sample seven different PCR reactions were performed which allowed the identification of all DPA1 alleles and the resolution of all DPA1 genotypes. Forty-eight cell lines and 100 donor spleen cells were investigated by the DPA1 PCR-SSP technique. In the forty-eight known workshop cell-lines no false positive or false negative results were obtained. The 100 donor spleen cells were only typed by the PCR-SSP technique and in their DNAs only one or two DPA1 alleles were found. Twenty cell lines and twenty donor spleen cells were typed on two separate occasions and interpreted blindly. The reproducibility between the repeated typings was 100%. The length of the specific products ranged from 103 to 258 base pairs and the amplification patterns obtained were easy to interpret. In conclusion, DPA1 typing by the PCR-SSP method is an accurate typing technique with high sensitivity, specificity and reproducibility. Analysis of the distribution of DPA1 alleles was performed in 100 Caucasian samples, 100 African samples and 80 Oriental samples, including separation of the four of HLA-DPA1 alleles. Each ethnic group appeared to have one (Caucasians), or two (Africans and Orientals), frequent DPA1 allele(s) and a high frequency of DPA1 homozygotes, suggesting that, like for the DPB1 locus, balancing selection does not appear to be affecting the evolution of the DPA1 locus.

Alleles↗
PubMed1996

Distribution of HLA-Dw2 in optic neuritis and multiple sclerosis indicates heterogeneity.

UNLABELLED: The human leukocyte antigen (HLA) phenotype Dw2 is known to be increased in multiple sclerosis (MS), but only slightly in optic neuritis (ON). MATERIAL AND METHODS: 127 consecutive patients with unilateral monosymptomatic ON were typed genomically for HLA-DR and -DQ genes. RESULTS: The frequency of HLA-Dw2 among ON patients (47%) was found to be significantly higher than among 250 controls (30%) but significantly lower than in a group of 245 MS patients (60%), all of the same ethnic origin. At the group level, these figures can be calculated to indicate that 53% of the ON patients belong to the group of "MS-type ON" (95% confidence limits 25-78%). A compilation of published data on the frequency of the HLA-DR17(3), DQ2 haplotype, prompted by a slight increase in this material, revealed a significant association with this haplotype in ON, after compensation for the increase of Dw2. CONCLUSION: ON differs from both MS and controls regarding HLA-Dw2. Thus, a substantial number of patients with ON may suffer from conditions not immuno-genetically related to MS, which might be designated as non-MS type ON. This condition may be more common in men and in young patients of both sexes.

Adult↗
PubMed1996

On T-cell recognition of nickel as a hapten.

T-cells recognize antigens as peptides associated with self-molecules encoded by genes of the HLA region. In patients with contact allergy to nickel, T-cells that are specific for non-peptide haptens have been described. Previously, we have isolated HLA class II-restricted nickel-specific T-cell clones from patients with nickel sensitivity. In this paper, data on the fine specificity of a nickel-specific HLA-DR4-restricted clone have been reevaluated. Genomic tissue typing employing polymerase chain reaction and sequence-specific primers were used. Nickel was presented to the T-cell clone by all three subtypes of HLA-DR4 included in our panel. Two different DRB4*0404-positive cells presented nickel, whereas only 3 of the 7 DRB1*0401-positive and one of the 3 DRB1*0408-positive cells restimulated the T-cell clone. These findings are compatible with the notion that nickel interacts with endogenous peptides in the antigen-presenting groove of the HLA molecule, thereby changing these peptides' antigenicity rather than their ability to bind to the HLA molecule. Variations of the endogenous peptide in the antigen-presenting groove as well as differences of the HLA molecules give the DR4 specificity of the nickel-specific clone MCE2.

Antigen Presentation↗
PubMed1996

Multiple basal cell carcinomas: no association with HLA-DRB, HLA-DQA1 or HLA-DQB1 in Swedish patients.

Many diseases with autoimmune features are associated with alleles of the human leucocyte antigen (HLA). However, few if any malignant disorders have reproducibly been shown to be HLA-associated. In three independent studies, using serological tissue typing techniques, an increase of the HLA class II specificity DR1 has been found in patients with multiple basal cell carcinomas. These observations prompted us to determine the frequencies of DRB1, DQA1, and DQB1 alleles by high-resolution genomic tissue-typing methods, including subdivision of the serological DR1 specificity in the four sequence-defined alleles, DRB1*0101 to DRB1*0104, in 50 unrelated Swedish patients with a history of four or more basal cell carcinomas and 250 healthy controls. The frequency of DR1 was the same in patients and controls (18%). All DR1-positive patients and controls carried the DQA1*0101 and DQB1*0501 alleles. Six of the nine DR1-positive patients and controls carried the DQA1*0101 and DQB1*0501 allels. Six of the nine DR1-positive patients were DRB1*0101-positive, one DRB1*0102 and two carried the DRB1*0103 allele. This distribution of DRB1*01 alleles did not differ from the one found in the controls. We conclude that genetic factors associated with the HLA class II region do not contribute significantly to the aetiology of multiple basal cell carcinomas.

Adult↗
PubMed1995

HLA-DR and HLA-DQ are not markers for rapid disease progression in primary sclerosing cholangitis.

BACKGROUND/AIMS: The association between primary sclerosing cholangitis (PSC) and the HLA haplotype A1, B8, DR3, DQ2 is well established. During the last few years, several additional HLA associations have been suggested in PSC. Furthermore, two different HLA-DR specificities have been reported to be markers for rapid disease progression. Our aim was to critically evaluate all of the current and as yet mostly unconfirmed HLA class II issues in PSC. METHODS: Seventy-five Swedish patients with PSC were HLA-DR and HLA-DQ genotyped. RESULTS: Of the recently described HLA associations in PSC, the association with the DRB1*1301, DQA1*0103, DQB1*0603 haplotype was decisively confirmed, whereas the DRB1*04 specificity was only slightly under-represented and the frequency of DR2 was neutral. The association with codon 38 of DRB genes was secondary to the DRB3*0101 association. HLA-DR and HLA-DQ alleles were not found to be markers of disease progression. CONCLUSIONS: The HLA-associated genetic susceptibility to PSC cannot be attributed to specific amino acid positions of the DR beta chains. The highly discrepant results obtained in two previously reported studies and the present investigation indicate that HLA class II alleles are not markers for a more aggressive clinical course in PSC.

Alleles↗
PubMed1994

T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.

Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4+ T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4+ and CD8+ lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V alpha 2.3+ CD4+ lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V alpha/V beta gene products analyzed in this study--V alpha 12, V beta 2, V beta 3, V beta 5.1, V beta 5.2/5.3, V beta 5.3, V beta 6.7, V beta 8.1, and V beta 12--were in general normally expressed by CD4+ T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3+ patients and found an association between the ratio bronchoalveolar lavage fluid/peripheral blood V alpha 2.3+ CD4+ T cells and clinical signs of disease activity. Finally, when analyzing TCR V gene usage by CD8+ bronchoalveolar lavage fluid and peripheral blood T cells, a normal V alpha 2.3 usage was found in all cases, but lung-restricted T-cell expansions using other TCR V gene segment products were identified.

Adult↗
PubMed1994

Presentation of the Plasmodium falciparum antigen Pf155/RESA to human T cells. Variations in responsiveness induced by antigen presenting cells from different but MHC class II identical donors.

The antibody response in humans naturally primed to a malaria vaccine candidate antigen (Pf155/RESA) is genetically regulated. Here, the impact of antigen presenting cells (APC) on the control of in vitro T-cell responses induced by Pf155/RESA or synthetic peptides corresponding to its major Pf155/RESA epitopes was studied. T cells and APC were from the peripheral blood of monozygotic or dizygotic twins and their age matched siblings, all living in the central highlands of Madagascar. When induced to proliferate (thymidine incorporation) in vitro by antigenic peptides, the T-cell responses varied less within the twin pairs than between them and their siblings or the entire group, implying that they were genetically regulated. Occasional MHC class II associations of some of the responses were weak and did not reflect underlying MHC class II restrictions. When T cells and APC from different but MHC class II identical donors were incubated in various combinations, antigen charged APC from homologous donors induced in vitro T-cell proliferation which differed from that induced by the T-cell donors' own APC. Pretreatment of the APC with either paraformaldehyde or anti-class II antibodies inhibited or abolished this antigen dependent T-cell proliferation. The results suggest that the observed differences in T-cell responses induced by APC from different donors reflect differences at the level of these cells. Whether they reflect differences in the proteases involved in antigen processing, in the costimulatory signals provided by the APC to the T cells or in the secretion of other regulatory factors remains to be elucidated.

Adolescent↗
PubMed1994

The HLA-Dw2 haplotype segregates closely with multiple sclerosis in multiplex families.

Multiple sclerosis (MS) is associated with the HLA class II specificity Dw2, but the importance of its influence has been questioned, since sib-pair analysis has failed to show linkage with this haplotype. However, the use of 'identity by descent' (IBD) analysis may not be ideal, since it does not make use of the facts that (i) the Dw2-haplotype is the only haplotype with a confirmed role in MS, and (ii) it performs its influence in a dominant manner. We have investigated nine Swedish multiplex MS families. In eight of the families, the Dw2 haplotype occurred in MS patients. Within these families, Dw2 was shared by all 17 individuals with MS. In a compilation of 48 published multiplex MS families in which at least one patient carried Dw2, only three of 107 individuals with MS did not carry the Dw2 haplotype. This indicates that the Dw2 haplotype, when present in familial MS, may confer a stronger influence in MS susceptibility than generally recognized.

Genes, MHC Class II↗
PubMed1994

Human antibody responses to Pfs 230, a sexual stage-specific surface antigen of Plasmodium falciparum: non-responsiveness is a stable phenotype but does not appear to be genetically regulated.

The 230 kD gamete surface protein of the malaria parasite Plasmodium falciparum (Pfs 230) is a target of transmission blocking antibodies. Anti-Pfs 230 antibodies are induced following natural infection with malaria but are not found in all P. falciparum-exposed individuals. In this study we have shown that approximately 40% of malaria-exposed Gambians do not make antibodies to the native Pfs 230 molecule. This phenotype is remarkably stable over time and does not appear to be related to age, malaria exposure or major histocompatibility complex genotype. Comparison of antibody responses in twins indicates that the anti-Pfs 230 response is not strictly genetically controlled, but a high degree of concordance within both dizygous and monozygous twin pairs suggests that factors associated with exposure to malaria in childhood may be important in determining the subsequent immune response.

Adolescent↗