Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers?

The aim of this study was to identify significant prognostic factors by using unrelated genomically HLA-A, -B and -DRB1-identical donors. Such data could help to choose the best donor. We studied 136 consecutive patients with hematologic malignancies and a median age of 32 years (range, 0-55 years) who received hematopoietic stem cell transplantation.

Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients.

Several lines of evidence suggest a genetic predisposition to sarcoidosis, and strong associations have been shown with the major histocompatibility complex gene complex. In this study on Scandinavian sarcoidosis patients, we investigated any influence on the outcome of disease by human leukocyte antigen (HLA) class I alleles alone and in combination with selected class II alleles. HLA-B*07 independently increased the risk for persistent sarcoidosis (odds ratio [OR], 1.

Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation.

In unrelated stem-cell transplantation, the value of matching at the HLA-A, -B and -DR loci between donor and recipient is well documented. The effect of HLA-C, DPB1 and DPA1 mismatches on transplantation outcome is unclear. In this study, 104 donor recipient-pairs, transplanted at Huddinge University Hospital between 1988 and 1999, were retrospectively HLA class I- and class II-typed by PCR-SSP.

Immunogenetic heterogeneity in single-system and multisystem langerhans cell histiocytosis.

Langerhans cell histiocytosis is a rare disease with an unknown etiology and poorly understood pathogenesis. Immunologic, viral, and proliferative clonality causes have all been considered. To determine whether Langerhans cell histiocytosis and its two main subgroups, single-system and multisystem disease, are associated with HLA-A, -B, -Cw, or -DR alleles, a total of 84 patients <15 y of age at the time of diagnosis and of Nordic origin were analyzed, 82 for HLA class I and 76 for HLA class II.

Lung restricted T cell receptor AV2S3+ CD4+ T cell expansions in sarcoidosis patients with a shared HLA-DRbeta chain conformation.

Background: Sarcoidosis is a systemic disease of unknown aetiology frequently affecting the lungs. CD4+ T cells, in particular, accumulate in the lungs, implicating them in the pathogenesis of the disease.

Methods: T cell receptor (TCR) variable (V) gene expression on bronchoalveolar lavage (BAL) fluid T cells and the HLA DR alleles of 121 Scandinavian patients with sarcoidosis was determined.

HLA-AB typing by polymerase-chain reaction with sequence-specific primers: more accurate, less errors, and increased resolution compared to serological typing.

Until recently, serological typing has been the primary technique used for HLA class I analysis. But because of limitations, molecular-typing techniques have replaced or supplemented the microlymphocytotoxicity test. It has been assumed that HLA class I serological typing was more accurate than serological HLA-DR typing; the latter has been shown to have 10-25% errors.

The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis.

Background: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression.

No human leukocyte antigen-A, -B or -DR association in Swedish patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a cicatrizing, inflammatory and recurrent disease restricted to inverse skin, such as that of the axilla and groin of younger adults. In a previous study, using serological tissue-typing techniques, no significant increases in the human leukocyte antigen (HLA)-A and -B specificities were found in patients with HS. The aim of this study was to determine the frequencies of HLA-A, -B and, for the first time, HLA-DR alleles, using genomic tissue-typing methods in patients with HS.

HLA-DPB1 typing by polymerase chain reaction amplification with sequence-specific primers.

DPB1 is the second most polymorphic class II locus with currently 84 recognized alleles, i.e. DPB1*0101 to DPB1*8101.

Analysis of intracellular cytokines in CD4+ and CD8+ lung and blood T cells in sarcoidosis.

In pulmonary sarcoidosis, activated T cells accumulate in the lungs. We hypothesized that the balance between the T-helper type 1 (Th1) cytokines (interferon [IFN]-gamma and interleukin [IL]-2) and Th2 cytokines such as IL-4, IL-5, and IL-10 might explain differences in clinical outcome in pulmonary sarcoidosis, such as why patients of human leukocyte antigen (HLA) type DR17 have a much better prognosis than those of other HLA types. Peripheral blood lymphocytes (PBL) and lymphocytes obtained by bronchoalveolar lavage (BAL) from HLA-typed sarcoidosis patients, as well as PBL from healthy controls, were stimulated in vitro, fixed, and permeabilized with saponin.

Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis.

Objectives: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin that mostly affects male patients with inflammatory bowel disease (IBD). The immune system is believed to be involved in the etiology/pathogenesis as these patients present with several immunological disturbances. Susceptibility to develop primary sclerosing cholangitis is partly determined by genes in the HLA complex.

HLA-DR15 is associated with lower age at onset in multiple sclerosis.

To date, more than a dozen studies have investigated the role of HLA genes in determining clinical course and disease severity in multiple sclerosis (MS); in each of these studies, however, patient sample size has been small, and no consistent pattern has emerged from the results. For the present study, we determined HLA class II genotypes and catalogued clinical and demographic data for a total of 948 patients, making our data set the largest ever used to investigate HLA genes in MS. Our goals were both to investigate the impact of HLA-DRB1 alleles on clinical course and disease severity in MS and to compare the frequencies of the established susceptibility allele DR15 in various clinicodemographic subgroups of MS patients.

Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease.

Multiple sclerosis (MS) is a presumed autoimmune disease of the central nervous system, shown to be associated with the HLA class II haplotype DRB1*15,DQB1*06. Carrying the HLA class II haplotype DRB1*15,DQB1*06 increases the risk of MS by 3.6.

Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis.

In previous reports of studies of Scandinavian sarcoidosis patients, we have described a strong association between lung-restricted expansions of T cells expressing T-cell receptor (TCR) AV2S3 and the human leukocyte antigen (HLA)-DRB1*0301 (DR17) and -DRB3*0101 alleles, suggesting the presence of a specific antigen in sarcoidosis. In the present study, the degree of lung-accumulated TCR AV2S3(+) T cells was related to clinical data in 51 HLA-DRB1*0301/DRB3*0101-positive Scandinavian patients with pulmonary sarcoidosis. Significantly more AV2S3(+) lung T cells (median: 30.

The CTLA-4 gene is associated with multiple sclerosis.

We have investigated whether three intragenic polymorphisms of the CTLA-4 gene, a C/T base exchange in the promoter (p.-318), an A/G substitution in exon 1 (p.49) and a dinucleotide repeat polymorphism in exon 4 (p.

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.

Low incidence of acute graft-versus-host disease, using unrelated HLA-A-, HLA-B-, and HLA-DR-compatible donors and conditioning, including anti-T-cell antibodies.

Background: Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD).

Methods: HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12).

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.

No linkage or association of a VNTR marker in the junction region of the immunoglobulin heavy chain genes in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system. Autoantibodies are though to participate in the pathogenesis. Previous reports on the role of immunoglobulin (Ig) variable gene segments in MS are contradictory.

Report from the HLA class II typing by PCR-SSP Multicentre Study.

Results from 360 HLA-DR and -DQ 'low-resolution' typings with polymerase chain reaction sequence-specific primers (PCR-SSP), performed by nine laboratories, were analysed for their overall utility in routinely defining the HLA-DR1-DR18, DR51-DR53 and DQ1-DQ9 specificities in less than 2.5 h. Thirty EDTA blood samples and 10 DNA samples were distributed and analysed by each laboratory.

Analysis of the T-cell receptor V beta usage in monozygotic and dizygotic twins living in a Plasmodium falciparum endemic area in west Africa.

To investigate the influence of genetic and/or environmental factors in the development and shaping of the human peripheral T cell repertoire the authors studied the T-cell receptor (TCR) V beta usage in 10 adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in West Africa. The TCR repertoire was determined using a small panel of anti-V beta specific monoclonal antibodies (MoAbs) using conventional immunofluorescence assays. The results revealed that the V beta repertoire was similar to that recently described for a Caucasian population using a similar panel of antibodies.

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.

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.

Preferential V beta3 usage by hepatic T lymphocytes in patients with primary sclerosing cholangitis.

Background/aims: Primary sclerosing cholangitis and primary biliary cirrhosis are two biliary destructive disorders characterized by prominent T lymphocyte infiltrates in areas of portal destruction. The specificity of the T cell is determined by the T cell receptor for antigens. The aim of this study was to investigate the preference by which certain V alpha and V beta gene segments are expressed by peripheral and hepatic T cells in primary sclerosing cholangitis and primary biliary cirrhosis.