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Biomedical subjects

E Möller

Publications and source records attributed to E Möller.

At least 145 records · Page 8Linked to original sources
PubMed1986

Further studies on psoriasis-associated HLA-Dw/DR7 using PLT cells primed against a familial psoriasis-linked HLA haplotype.

The products of the HLA-D region and their correlation to psoriasis vulgaris was studied using the primed lymphocyte typing (PLT) assay. In families with one healthy and one psoriatic parent and one psoriatic child primary MLC (mixed lymphocyte culture) stimulation was carried out between responder cells from the healthy parent and stimulator cells from the psoriatic child. In this way 21 PLT reagents directed against putative psoriasis-associated lymphocyte activating determinants were produced. Three reagents that gave clear bimodal stimulation patterns against lymphocytes of 51 psoriasis patients were further tested against 78 controls. Specificity of these reagents was studied using homozygous typing cells (HTC's) as stimulators. Compiled data show that cells from DR7 positive psoriatic patients give higher restimulation of these PLT reagents than do cells from healthy DR7 positive controls. In addition, a higher frequency of psoriasis patients compared to controls gave significant restimulation. Therefore we concluded that these PLT reagents recognized at least partly different DR7 associated determinants in the psoriasis patients and in controls. The reason is either that psoriasis patients carry a different lymphocyte activating DR associated specificity or, alternatively, that restimulation was caused by products of a distinct psoriasis associated locus in linkage disequilibrium with D/DR7 or of a determinant recognized together with D/DR7 as a restriction element. These data further support the notion that psoriasis is a disease with primary HLA associations to both class I and class II MHC genes.

Alleles↗
PubMed1986

Pacemaker treated women with heart block have no increase in the frequency of HLA-B27 and associated rheumatic disorders in contrast to men--a sex linked difference in disease susceptibility.

HLA-B27 associated rheumatic syndromes have been found in 13% of more than 200 pacemaker treated Caucasian men. Furthermore, a significantly increased frequency of HLA-B27 was found in pacemaker treated men without HLA-B27 associated rheumatic disorders. Consequently, an HLA-B27 associated disease process seems to be the cause of heart block development in 15 to 20% of Caucasian pacemaker treated men. The purpose of our study was to find out if the HLA-B27 associated disease process was equally common in pacemaker treated women. Eighty-five pacemaker treated women with second and third degree heart block were HLA typed for B27, and HLA-B27 positive individuals were further examined for the presence of associated rheumatic disorders. HLA-B27 was present in 7 women, 8.2%, similar to the frequency in the general population, and none of them had an associated rheumatic disease. Thus, there is a significant sex linked difference in the susceptibility to HLA-B27 associated heart block.

Adult↗
PubMed1985

HLA antigens and adverse drug reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis.

The association between HLA antigens and adverse drug reactions (ADR), (e.g. proteinuria, haematological abnormalities, stomatitis, diarrhoea and dermatitis) in rheumatoid arthritis (RA) to sodium aurothiomalate (gold) and to D-penicillamine (PA) were studied in 32 patients. Thirty-eight RA patients treated with gold and PA, and with no ADR to these drugs, were used as controls. The frequency of HLA B8 was significantly (p less than 0.05) increased among RA patients with ADR compared to plasma donors. DR3 was also significantly increased (p less than 0.05) in RA patients with haematological ADR compared to plasma donors. Haematological ADR occurred significantly (p less than 0.05) more often in DR3 positive patients (55%) than among DR3 negative RA patients (27%).

Adult↗
PubMed1985

HLA genotypes in two three-generation families with rheumatoid arthritis.

Two three-generation families from Northern Sweden with rheumatoid arthritis (RA) were clinically examined. Tissue typing was performed for HLA-A, -B, -C, and -DR antigens. No disease-associated haplotype could be defined within these families. Six of nine members with RA were HLA-DR4 positive. Both families had a HLA-DR4 containing haplotype in the first generation and second-generation members married DR4 positive individuals, which probably increased the risk to develop RA in the third-generation members.

Adolescent↗
PubMed1985

T and B lymphocytes in patients with nickel sensitivity.

Peripheral blood mononuclear cells from altogether 45 nickel-sensitive patients and 37 controls were assayed for various T and B cell variables. All the patients, but none of the controls, fulfilled our in vitro criteria for a positive response to nickel sulphate (NiSO4). We report normal T and B lymphocyte counts, normal spontaneous plaque-forming cell (PFC) numbers, normal serum immunoglobulin levels, and no demonstrable specific cytotoxic T lymphocyte activity associated with nickel sensitivity. We could detect only a slight increase in the number of PFC and in the number of cytoplasmic immunoglobulin positive (cIg+) cells following stimulation of the patients' cells with NiSO4 for 6 days in culture. Apart from a transient increase in the [3H]thymidine uptake by patients' cells stimulated with NiSO4 in vitro, and a transient drop in the OKT4/OKT8 ratio, there were no major differences in the values of the above variables before and after in vivo challenge of 3 patients with NiSO4. Blood from only 2 of the latter 3 patients was tested in the DNA synthesis test. We conclude that apart from the DNA synthesis test, none of these tests is of any use as an aid to diagnosis in patients with nickel sensitivity. A careful attitude towards patch testing should be maintained.

Adult↗
PubMed1985

HLA-class II restriction of the proliferative T lymphocyte responses to nickel, cobalt and chromium compounds.

Peripheral blood mononuclear cells from nickel and/or cobalt or chromium sensitive patients were stimulated with the appropriate metal compound for 7 days in culture. The transformed blasts were separated from non-transformed small cells on Percoll density gradients. The blasts, maintained in interleukin-2 containing medium and enriched for T cells, were both antigen specific and devoid of alloreactivity. The metal compound primed T cell blasts from all patients showed a good proliferative response on restimulation with the priming compound in the presence of autologous adherent cells (AC). Analysis of HLA class II phenotypes of allogeneic AC that could serve as antigen presenting cells indicated that responsiveness of T cell blasts from most but not all patients could be explained on the basis of HLA-DR as a restricting element. We conclude that products of other class II loci (HLA-DQ and/or HLA-DP) might also serve as restricting elements for a secondary in vitro proliferative response to these metal compounds.

Antigen-Presenting Cells↗
PubMed1985

Implication of structural class II gene polymorphism for the concept of serologic specificities.

We have used DNA-DNA hybridization methods to study the relationship of genetic polymorphisms to the established HLA-D region determinants as detected with serological reagents. The supertypic determinants DRw52 and 53 are closely associated with a particular RFLP detected with the DR beta probe, but are seemingly encoded by a distinct beta gene compared to the "conventional" DR antigens. DQw1 is closely associated with a DQ alpha chain polymorphism, whereas the DQw2 and 3 specificities have correlations to RFLP using the DQ beta probe. Additional DQ polymorphism, in linkage disequilibrium with DR but yet without a serological counterpart is also described. Considering the finding that there exist a varying number of DR beta genes in different DR haplotypes (Böhme et al. 1985), from 1 in DRw8 to 3 (or 4) in DR4- and DR7-positive cells, we have made a tentative re-evaluation of the genetic basis for the conventional DR specificities. The combination of cell surface antigens encoded by DR and DQ loci are believed to form the basis for MLC stimulating determinants. We have speculated that a combination of determinants encoded by distinct DR beta genes and in certain instances additional DQ polymorphism is responsible for the DR types. Thus, only a limited variability is observed after DNA-DNA hybridization using DR beta probes. Only DR1-, 2- and 4-positive cells have distinct bands not detected in any other haplotypes, whereas DR3, 5, w6, and w8 can be characterized by a combination of bands, which is the result of hybridization with several DR beta genes. Furthermore, we have suggested that the difference between the DR3 and DRw6 specificities is due to variability with regard to 1 DQ beta gene, and have also made the assumption that DRw6 cells may express a lower concentration of DR locus encoded products compared to DR3-positive cells (Haziot et al. 1985). In addition, we have discussed the genetic basis for so-called DR blanks, implying that an unorthodox combination of DR and DQ determinants forms the basis for difficulties in assigning DR types to such cells in some cases and that "blanks" can be associated with low expression at the cell surface of well-known DR determinants. The use of cDNA and genomic probes for distinct class II genes to elucidate the mechanisms of HLA and disease association has been documented and discussed.

Alleles↗
PubMed1985

Effect of drug therapy on circulating and synovial fluid Ig-secreting cells in rheumatoid arthritis.

A common immunological abnormality in rheumatoid arthritis (RA) is an increased spontaneous polyclonal B cell activation. In order to study the influence of drug therapy in RA on the functional activity of B cells we enumerated spontaneous plaque-forming cells (PFC) in peripheral blood lymphocytes (PBL) and synovial fluid lymphocytes (SFL) by a reverse haemolytic plaque assay. Spontaneous IgG-, IgM-, and IgA-PFC in PBL of 26 patients with classical erosive RA receiving either gold salts or D-penicillamine were similar to those observed in 20 healthy controls. In contrast, significantly higher numbers of IgG- and IgA-PFC, but not IgM-PFC, were found in PBL of nine patients with classical erosive RA receiving non-steroidal anti-inflammatory drugs (NSAID) alone. Furthermore, spontaneous PFC in SFL from 16 consecutive patients with RA receiving second-line drugs, as well as 17 patients with other forms of arthritis (non-RA) were generally low and significantly less than those observed in 20 RA patients on NSAID alone. Moreover, a wide individual variation in PFC, especially in relation to the IgG class, was recorded in the synovial lymphocytes. These studies imply that treatment with second-line drugs is associated with normalisation of B cell activity in RA patients, and that the effect can be detected at the cellular level both in blood and synovial fluid.

Adult↗
PubMed1985

An outbreak of coxsackievirus B infection followed by one case of diabetes mellitus.

During the fall of 1979, 22/250 Swedish UN soldiers serving in Egypt were hospitalized with fever and gastroenteritis associated with aseptic meningitis. One of the 22 developed insulin dependent diabetes mellitus (IDDM) 10 weeks following the infection. The majority of the 22 patients showed significant titer rise for coxsackievirus B by plaque reduction neutralization test. The serology results indicate that coxsackievirus B4 most likely caused the outbreak. All 22 were also tested for islet cell cytoplasmic antibodies and islet cell surface antibodies and found negative. The individual developing diabetes mellitus had the HLA-DR phenotype 3,4, which is associated with IDDM.

Adult↗
PubMed1985

HLA antigens in rheumatoid arthritis patients with and without a family history of polyarthritis.

The HLA antigens, A, B and DR, were studied in 141 patients with erosive, seropositive rheumatoid arthritis (RA). The frequency of the B27 antigen was significantly increased among patients with a family history of symmetrical polyarthritis compared with blood donor controls (p less than 0.001) and with patients without a family history of polyarthritis (p less than 0.005). The frequency of DR4 was significantly (p less than 0.001) increased among the RA patients, but there was no significant association between DR4 and a family history of polyarthritis.

Arthritis↗
PubMed1985

Clinical symptoms and HLA antigens in a family with Reiter's disease.

A clinical and immunogenetic study was performed on a three-generation family with Reiter's disease (RD). Twelve of 56 members of the family (33 clinically examined) including one in-law, had symptoms of arthritis, urethritis, conjunctivitis, uveitis, and/or mucocutaneous manifestations, but only one had the complete triad of Reiter's syndrome (RS). Radiographic sacro-iliitis was found in 7 individuals, and monoarticular onset was reported in 5 out of 7 with peripheral arthritis. HLA B27 was found in 26 of the 37 family members who were tissue typed (including one in-law). All individuals with RD were B27-positive. Seven different B27 phenotypes were identified. This finding suggests that RD is associated with the B27 antigen itself, and not to a gene closely linked to B27. From a pedigree analysis of this family an autosomal dominant inheritance with incomplete penetrance or multifactorial inheritance seemed the most probable alternatives. The family history is a useful adjunct in the diagnosis of RD.

Adolescent↗
PubMed1985

HLA-DR beta genes vary in number between different DR specificities, whereas the number of DQ beta genes is constant.

Probes isolated from DR and DQ beta cDNA and genomic clones were used in hybridizations to restriction enzyme-digested DNA from human homozygous typing cells (HTC) as well as other DR homozygous cells in order to estimate the number of beta genes in the DR/DQ class II region. Varying numbers of DR beta genes were found in HTC of different DR specificities, from possibly one in DR 8 cells to three in cells of DR 2 to 7. The DR beta genes of different specificities seem to be related to one another in a distinct fashion. In contrast, all HTC contain two DQ beta genes per chromosome. The restriction site polymorphism of DQ beta genes is considerably more extensive than that of DQ serology, although one of the genes seems to be nonpolymorphic. In addition to the two DP beta genes identified previously, a minimum of three to five DQ and DR beta genes exist in the human haploid genome.

DNA Restriction Enzymes↗
PubMed1985

HLA haplotypes in a family with ankylosing spondylitis and rheumatoid arthritis.

HLA haplotypes (including A, B, C and DR loci) were studied in a family with members who had both rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Sacroiliitis was found in 7 family members, one of whom had AS and 2 others erosive, seropositive RA. They carried the B27-DR4 haplotype, suggesting a possible dual genetic association of the same haplotype in both RA and AS. Three other different HLA-B27 containing haplotype were found, 2 of which could be associated with sacroiliitis/AS. Within this family sacroiliitis and/or AS rather seemed associated with the B27 antigen itself than with the same haplotype.

Adult↗
PubMed1984

Genomic hybridization with class II transplantation antigen cDNA probes as a complementary technique in tissue typing.

Hybridizations of HLA-DR and DC transplantation antigen beta chain cDNA probes to restriction enzyme digested genomic DNA were examined in regard to their potential in tissue typing. DNA from cells, typed by cellular techniques to be homozygous for the specificities Dw 1 to 8, gives rise to unique fragment patterns for each specificity. Hybridizations to DNA from unrelated individuals serologically typed to be DR identical occasionally reveal genetic differences in the class II antigen region, notably with the DC beta cDNA probe. In contrast, hybridizations to DNA from monozygotic twins displayed completely identical patterns with both types of probes. From these data it seems reasonable to conclude that genomic hybridizations with class II antigen probes will be useful in the definition of new class II antigen loci and alleles, in determination of paternity, in studies of class II antigen linked diseases and as a complementary method in conventional tissue typing.

Alleles↗
PubMed1984

Adjuvants influence the immunoglobin subclass distribution of immune responses in vivo.

Mice were immunized against fluorescein isothiocyanate (FITC)-labelled human gamma globulin (HGG) in the absence or presence of different adjuvants. The immune response was assayed every other day with regard to both total Ig-secreting cells and FITC-specific plaque-forming cells (PFC). The adjuvants influenced the type of immune response induced to the same antigenic determinant. Thus, addition of Freund's complete (FCA) or incomplete (FIA) adjuvant preferentially led to the secretion of IgG1 PFC of an average high affinity. Most newly appearing IgG-secreting cells were also detected as FITC-specific PFC. The use of lipopolysaccharide (LPS) as an adjuvant resulted in the induction of both IgM and IgG, particularly of the IgG3 and IgG2b subclasses. However, these antibodies had relatively low affinity, and a large number of total IgG-secreting cells induced by LPS had no detectable FITC specificity. The FCA/FIA- and LPS-induced responses to FITC-HGG were additive when injected together, indicating that they act on distinct subpopulations of B lymphoid cells. The adjuvant response to LPS, but not the response to FCA/FIA, was totally absent in mice of the C3H/Hej strain, which are non-responders to the polyclonal activating properties of LPS. Finally, the response induced by FCA or FIA was T-cell-dependent and the LPS response T-cell-independent as assayed in nude mice.

Adjuvants, Immunologic↗