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Biomedical subjects

A Svejgaard

Publications and source records attributed to A Svejgaard.

At least 181 records · Page 10Linked to original sources
PubMed1988

Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide.

The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF beta (lymphotoxin). The intracellular levels of bioactive TNF alpha were minimal or undetectable in all cases. Cells from HLA-DR2+ individuals secreted significantly lower amounts of TNF alpha than cells from HLA-DR2- donors [2 ng/ml (1.5-4.4) and 7.5 ng/ml (3.9-8.3) respectively (medians 25-75%); P less than 0.01]. The difference disappeared if the cells were preactivated for 2 days with 1000 U/ml of recombinant gamma interferon (rIFN-gamma). In some individuals, the TNF alpha response increased considerably after IFN-gamma priming, in particular in those possessing the HLA-DR2 antigen. In contrast, there was no detectable difference in the production of IL-1 beta between the donors, and the IL-1 beta response decreased significantly after rIFN-gamma priming in HLA-DR2+ individuals [2.3 ng/ml (1.1-8.4) versus 7.2 ng/ml (5-7.9); P less than 0.05] and in HLA-DR2- individuals [3 ng/ml (1.1-5.3) versus 5.7 ng/ml (3.9-7.5); P less than 0.01]. There was no correlation between the TNF alpha and IL-1 responses and any of the other HLA-DR, -DP, or -B antigens. There was a significant positive correlation between the levels of TNF alpha measured by ELISA and by cytotoxicity assay. However, the TNF alpha-containing supernatants from 9 out of 37 individuals appeared to contain inhibitor(s) of the biological activity of TNF alpha. The presence of inhibitor(s) was not associated with any HLA antigens.

Adult↗
PubMed1988

Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules.

Recent investigations have demonstrated that the primary mixed lymphocyte reaction (MLR) is dependent on certain accessory molecules, e.g. CD4 and LFA-1. We have compared the requirements of the primary MLR and the responses of alloreactive, primed lymphocytes (PL) by inhibition studies using monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c-reactive MoAb significantly inhibited the primary MLR (inhibition = 25%, P less than or equal to 0.01; 48%, P less than or equal to 0.01 and 13%, P less than or equal to 0.05, respectively) but these MoAb did not inhibit the primed lymphocyte reaction (PLR). The CD11b-reactive MoAb had no significant influence on either of the responses. CD2- and CD4- reactive MoAb significantly inhibited both primary MLR (greater than 80%, P less than or equal to 0.01) and to a lesser extent the PLR (40-65%, P less than or equal to 0.01). A MoAb reactive with IL-1 beta inhibited the primary MLR (38%, P less than 0.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data indicated that PL seemed neither to bind exogenous IL-1 (as opposed to CD4+ PBMC) nor to possess membrane-bound IL-1. The differences between 'virgin' and primed, allogeneic T-cell responses indicate that profound changes in the functional capability of the responding T-cell population take place during the bulk expansion. The results indicate that during repeated priming with alloantigen and bulk expansion, the proliferative response of T lymphocytes becomes independent of (i) the interaction with the CD11 adhesion molecule(s), (ii) the CD5 molecule, and (iii) the cytokine IL-1 beta.

Antibodies, Monoclonal↗
PubMed1988

Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences.

The secretions of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPS)-stimulated human monocytes (M phi) were investigated in an endotoxin (ET)-free milieu (less than 1.6 pg LPS/ml). Human M phi cultures from nine healthy men were stimulated with 0, 12.5-500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22-24%, intra-assay variation 3-7%). Spontaneous M phi secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these M phi products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR1,2-positive, were identified. Three first-degree relatives of the DR1,2-positive low-responder had similar low responses. Furthermore, M phi cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2,2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated M phi were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.

Biological Products↗
PubMed1988

HLA-DP antigens are involved in the susceptibility to multiple sclerosis.

Forty-five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA-DP using Primed Lymphocyte Typing. Thirty-nine MS-patients and 63 controls were also DNA-typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA-DP and -DR genes. The frequencies of DPw4 were 93.3% in MS patients and 72.3% in controls (relative risk, RR = 5.4, p = 0.0014). The DR2 antigen was present in 75.5% of the patients and in 33.7% of the controls (RR = 6.1, p less than 10(-6)). DPw4 was not associated (i.e., was not in linkage disequilibrium) with DR2 in patients or controls. Thus, in MS the associations with DP and DR are independent of each other. However, the combined presence of DPw4 and DR2 gave a significantly higher risk than each antigen alone, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to MS.

HLA-D Antigens↗
PubMed1988

Autoimmunity related to IgM monoclonal gammopathy of undetermined significance. Peripheral neuropathy and connective tissue sensibilization caused by IgM M-proteins.

In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three of them, including two siblings with a demyelinating peripheral neuropathy, the IgM was bound to the myelin-associated glycoprotein (MAG) of peripheral nerves. One had axonal neuropathy with IgM activity against the peri- and endoneurium, while another case with post-infectious neuritis had IgM activity against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported.

Aged↗
PubMed1987

Complement C3b receptors on erythrocytes in patients with juvenile rheumatoid arthritis.

Forty patients with juvenile rheumatoid arthritis (JRA) were examined for C3b receptor (CR1) levels on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation-complement consumption method), C3d split products (by intermediate gel rocket immunoelectrophoresis), and HLA-A, B, and C (by microdroplet lymphocytotoxicity test). Lower CR1 levels were found predominantly among patients with JRA (mean 57%) compared with 40 age-matched controls (mean 68%) (P = 0.008). The CR1 levels differed when the JRA patients were grouped by mode of disease onset and by clinical state at the time of testing (levels in patients with pauciarticular disease were higher than those in patients with polyarticular disease, and levels in patients with polyarticular disease were higher than those in patients with systemic disease) or by sex (girls had higher levels than boys; P = 0.01). The levels of circulating IC and C3d were elevated in 25% and 40% of JRA patients, respectively, and were mutually correlated (P less than 0.05, tau = 0.20). A negative correlation was found between levels of C3d and the numbers of CR1 (P less than 0.01, tau = -0.28), but concentrations of circulating IC did not correlate with CR1 values. CR1 levels were the same in 6 HLA-B27 positive and 25 HLA-B27 negative patients. These findings do not represent conclusive evidence that the number of CR1 on erythrocytes serves as a predictor of disease severity or as an indicator of disease activity in patients with JRA.

Adolescent↗
PubMed1987

Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes.

The restriction fragment length polymorphism (RFLP) of the class II HLA-DP subregion of the major histocompatibility complex (MHC) of humans has been unraveled by Southern blotting using DP alpha and DP beta probes in a study of 46 unrelated individuals with known HLA-DP types. Contrary to earlier preliminary findings with a limited number of enzymes, the RFLP appears to be quite extensive both with the DP beta (14 different DNA markers defined by individual fragments or clusters thereof) and the DP alpha (8 markers) probes, especially when enzymes recognizing only four base pairs were used. A few markers were absolutely or strongly associated with individual DP antigens, whereas most were associated with two or more DP antigens as defined by primed lymphocyte typing. Thus, Southern blotting seems feasible for typing for most DP determinants by specific fragments or subtraction between the various more broadly reactive DNA markers, and the RFLP provides further information on the DP subregion in addition to that provided by primed lymphocyte typing. In two recombinant families, the DP beta and DP alpha DNA markers segregated with DP antigens, whereas the DR beta, DQ beta, DQ alpha, and DX alpha markers followed the DR and DQ antigens.

Chromosome Mapping↗
PubMed1987

Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes.

The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors.

Adult↗
PubMed1987

The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells.

Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR) and antigenic stimulation by irradiated (7600 rad) post-BMT cells was observed in about two-thirds of the combinations tested (N = 20 and N = 9). The suppression of donor MLR and antigen responses ranged between 5-52% and 10-46%, respectively. Irradiated post-BMT cells significantly suppressed donor responses to suboptimal concentrations of phytohaemagglutinin (PHA) (median suppression: 28%; P less than 0.05; N = 7) and concanavalin A (Con A) (median suppression: 31%; P less than 0.05; N = 6). A clearly suppressive effect of post-BMT cells was observed when the ratios of CD4+/CD8+ post-BMT cells were lower than 0.5 (P less than 0.01). In three experiments, the depletion of the CD8- but not of the CD4-positive subset abrogated the suppression of the donor MLR by post-BMT cells. The suppression by post-BMT cells (irradiated) of MLR and mitogen responses was comparable whether the responding cells were derived from the donor or from HLA-DR-incompatible, unrelated individuals. The proliferative capacity of post-BMT cells compared to that of donor cells was assayed in the MLR with unrelated, HLA-DR-incompatible stimulator cells. A significantly decreased proliferative capacity (median 20% of that of donor cells) was found (P less than 0.01; N = 16). A weak inverse correlation (P less than 0.05; N = 16) between the proliferative and the suppressive capacity of post-BMT cells in the MLR was observed. These findings indicate that the decreased proliferative capacity upon mitogen, antigen, and alloantigen stimulation observed in most patients within 1-6 months after BMT may be partly due to non-specific suppression by CD8+ cells.

Adolescent↗
PubMed1987

A "new" supertypic HLA-DP related determinant detected by primed lymphocyte typing (PLT).

Primed Lymphocyte Typing (PLT) with local (CDP) and the 9th International Histocompatibility Workshop reagents (GNN) revealed "cross-reactions" between HLA-DPw6 and the GNN2B but not other DPw2 PLT-cells (GNN2A, CDP2A, CDP2B). We raised and bulk-expanded a well discriminating PLT-reagent (the JET-reagent) from an HLA-DR identical, DP, GNN2A, CDP2A, CDP2B compatible and GNN2B incompatible responder/stimulator combination. The JET-reagent defined a "new" determinant, JET, which was present in 11% of Danes. The JET determinant was associated with DPw2, w6, and DP-blank: 66% of DPw6 and DP-blank and 20% of DPw2-positive individuals were JET-positive. All JET-positive individuals belonged to this group, and six of these had two DP-antigens. JET segregated with DP-blank in three and with DPw6 in two informative families. In an HLA-DR/DPw6 recombinant family, JET segregated with DPw6 in the recombinant haplotype. The JET PLT-responses against all of six different JET-positive stimulators including the specific stimulator were strongly inhibited by the monoclonal antibody (MoAb) Tü39, which preferentially reacts with DP-molecules, but not by other HLA-specific MoAbs. The results indicate that JET is either a "new" supertypic DP-related specificity or a determinant, which shares epitopes with DP, of a "new" locus and in linkage disequilibrium with DP.

Antibodies, Monoclonal↗
PubMed1987

Increased frequency of HLA-DPw3 in severe aplastic anemia (AA).

Thirteen patients with severe aplastic anemia (AA) were HLA-DP typed using primed lymphocyte typing (PLT). The frequency of HLA-DPw3 was significantly increased to 69% in AA as compared to 22% in 160 controls (p less than 0.001; corrected p less than 0.01, RR = 8.0).

Adolescent↗
PubMed1987

HLA-DR factors associated with postpartum hypothyroidism: an early manifestation of Hashimoto's thyroiditis?

Thirty-three Danish women selected from a prospective study of postpartum thyroiditis were HLA-DR typed. All women had positive titers of antimicrosomal antibodies, and 20 women developed thyroid dysfunction after delivery. DR5 and the phenotype 4.5 were significantly increased in the whole group (p less than 0.001) and strongly associated to hypothyroidism (p less than 0.01), whereas DR3 was insignificantly increased in thyrotoxic women. It is concluded that postpartum hypothyroidism is an autoimmune disorder and may be an early manifestation of Hashimoto's thyroiditis.

Female↗
PubMed1987

HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease.

Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP incompatible BM, but in none of five recipients of DP-compatible BM. This difference was highly significant (p less than 0.001, Fisher's exact test). Moreover, severe acute GVHD was significantly increased in recipients of haploidentical, DR compatible, but DP incompatible BM as compared to severe acute GVHD in 88 recipients of HLA-identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play a role as transplantation antigens.

Bone Marrow Transplantation↗
PubMed1987

Immunological reclassification of 22 children with a former diagnosis of non-T, non-B ALL.

Stored peripheral blood or bone marrow mononuclear cells from 22 pediatric patients with verified acute lymphoblastic leukemia (ALL) previously classified as non-T, non-B ALL were re-investigated by flow cytometric analysis by means of a panel of B cell-specific and -associated monoclonal antibodies (moabs) using a new analytical method described by Platz et al, the so-called Delta Channel Value method. All 22 patients were immunologically re-characterized as pre-B ALL. The reproducibility between the first (acute) and subsequent re-analysis was almost complete. 20 of the tumor cell populations could be assigned to the B cell differentiation scheme recently proposed by Nadler et al. This scheme operates with four stages of pre-B cell differentiation and each stage is defined by the expression of one to four of the following markers: HLA-DR, CD19, CD10 and CD20. Two additional markers, CD24 and CD22, were investigated in our study and allowed further subdivision of the four subgroups proposed by Nadler et al. The composition of a panel of moabs for routine classification of pre-B ALL is proposed.

Adolescent↗
PubMed1987

Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis.

The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 patients with active juvenile chronic arthritis (JCA), 10 patients with JCA in remission, and 11 age matched, healthy controls. In addition, the distribution of T 'helper/inducer' (CD4+), T 'suppressor/inducer' (CD4+, Leu8+), T 'suppressor/cytotoxic' (CD8+), and 'natural killer' (NK) cells (CD16+) was studied. Twenty patients and six controls were investigated for the capability to stimulate alloreactivated primed lymphocytes. The prevalence of VLA-1 positive, large cells was significantly increased to 5% (median value) in active JCA as compared with JCA in remission (2%, p less than 0.05) and controls (1%, p less than 0.05), whereas no significant difference between JCA in remission and controls was observed. Except for two patients with active JCA, less than 1% IL2 receptor bearing cells were found in patients with JCA and controls. No significant difference in the prevalence and expression of the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA, JCA in remission, and controls. The prevalence of T suppressor/inducer (CD4+,Leu8+) cells was higher in remission JCA (17%) than in active JCA (11%) and controls (10%). This increase, however, did not reach statistical significance. In conclusion, late stage but not early stage T cell activation antigens were increased in patients with active JCA as compared with patients with JCA in remission and control, whereas some patients in remission had an increased prevalence of T suppressor/inducer cells.

Adolescent↗
PubMed1987

HLA associations in insulin-dependent diabetes mellitus diagnosed during pregnancy.

Sixty out of 63 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed during pregnancy in the Diabetes Centre at the Department of Obstetrics and Gynaecology, Rigshospitalet, Copenhagen, were re-examined 2-16 years after diagnosis. Fourty-six patients were currently insulin-treated and the remaining 14 patients were all severely glucose intolerant. HLA-typing was carried out in 41 of these patients. The HLA phenotype distribution showed a highly significant difference from that of non-diabetics but was similar to that seen in IDDM not related to pregnancy. Thus, pregnancy may constitute a special trigger mechanism for IDDM, but the subsequent pathogenic mechanisms are probably the same as those involved in other cases of IDDM.

Diabetes Mellitus, Type 1↗
PubMed1987

Immunological studies in acquired immunodeficiency syndrome: effect of TCGF and indomethacine on the in vitro lymphocyte response.

We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls. While low amounts of TCGF reduced the response of peripheral blood mononuclear cells (PBMC) to allogeneic cells in both healthy controls and AIDS patients, large amounts of TCGF augmented the response in both groups, although the response of the patients' cells were still subnormal. By depleting the PBMC for either CD4-positive or CD8-positive cells, the effect of TCGF on suboptimally mitogen-stimulated PBMC from controls was shown to be due to an increased response in both the CD4-positive and the CD8-positive cells. In contrast, with patient cells, TCGF only increased the response of the CD4-positive cells, while that of the CD8-positive cells was largely unchanged. Thus, the lack of normalization of the mitogen response of patient cells upon addition of TCGF may be largely due to unresponsiveness of CD8-positive cells to TCGF. This observation further supports the idea that CD8-positive cells are abnormal. To investigate the role of the inhibitor of TCGF production, PGE2, in AIDS, indomethacine was added to cultures of mitogen-stimulated PBMC from controls and patients. No differences were found between the three groups: the responses to PHA were slightly increased and those to Con A were unchanged.

AIDS-Related Complex↗