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Biomedical subjects

A Svejgaard

Publications and source records attributed to A Svejgaard.

At least 217 records · Page 12Linked to original sources
PubMed1985

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells.

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post-BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor cells in mixed lymphocyte cultures to HLA-DR-different third-party cells was suppressed by highly X-irradiated post-BMT cells by approximately 40%. Addition of T-cell growth factor (= interleukin 2 (IL-2)) or X-irradiated donor cells to post-BMT lymphocytes partially restored the mitogenic response. These findings indicate that the early post-BMT cells lack production of IL-2 but are capable of responding to IL-2 and that the almost extinct mitogen response of these cells is due to immaturity rather than active suppression. The suppression of the allogeneic but not the mitogenic response might be explained by differences in the modes of activation; for example, the allogeneic response must involve the T-cell receptor, while the mitogenic response may not.

Bone Marrow Transplantation↗
PubMed1985

Post transfusion purpura and anti-Zwb (-P1A2).

The first two cases of post transfusion purpura (PTP) due to recognized antibodies against the platelet specific antigen Zwb (P1A1) are described. In both cases, the antibodies were detectable in the platelet enzyme immuno-assay (ELISA), while the platelet specific alloantibodies could be ascertained neither in the platelet suspension immunofluorescence test (PSIFT) nor in the platelet fixation test (CFT) due to coexisting potent multispecific HLA-antibodies. The two sera reacted in parallel (coefficient of correlation, r = 0.87; P less than 10(-5) and the reactions of the two sera were negatively associated with the Zwa-antigen (P = 0.0002 and 0.003, respectively). Thus, PTP may be caused not only by anti-Zwa (-P1A1) but also by anti-Zwb.

Aged↗
PubMed1985

Studies of HLA-ABC and DR antigens in pure atopic dermatitis and atopic dermatitis combined with allergic respiratory disease.

The HLA-ABC antigens were investigated in 29 patients with pure atopic dermatitis and 43 patients with atopic dermatitis combined with atopic respiratory disease (ARD). Furthermore, the DR antigens were studied in 10 patients with dermatitis alone and in 24 patients with combined atopic disease. The frequencies of antigens and the HLA phenotypes A1, B8 and A3, B7 in the entire group of patients and in two subgroups did not differ significantly from those in controls, when correction was made for the number of comparisons made. However, the frequency of HLA-DR7 was strikingly low, but this observation needs confirmation. IgE levels were measured in eight patients with pure dermatitis and in 24 patients with dermatitis combined with ARD and found equally increased in both groups compared to controls.

Adolescent↗
PubMed1985

HLA antigen frequencies in juvenile chronic arthritis.

HLA-A, B, C, D, and DR typing was performed in 104 patients with Juvenile Chronic Arthritis (JCA). The majority of these (88 patients) participated in a follow-up study of a series of consecutive patients including patients in remission. The study confirmed that JCA is positively associated with B27, Dw8, and possibly Dw5, and negatively associated with Dw2 and Dw7. In JCA patients in remission, the frequency of Dw4 was significantly decreased to 5.0%, compared with 25.0% in healthy Danes and 23.7% in JCA patients with active disease. In pauciarticular onset JCA, the frequency of Dw4 was significantly decreased to 8.1% compared with 25.0% both in controls and in polyarticular onset JCA. These data indicate that Dw4 may be a risk factor of chronicity and multiple joint involvement in JCA. Chronic iritis was present in 18.2% of Dw8-positive patients, compared with 7.0% in Dw8-negative patients, and the frequency of Dw8 was 50.0% in JCA patients with chronic iritis. Thus, Dw8 may be a risk factor of chronic iritis in JCA. Genetically, three distinct subgroups seem to exist: (i) a B27-associated group; (ii) a D/DR5- and D/DRw8-associated group, and (iii) a D/DR4-associated group.

Adolescent↗
PubMed1985

The impact of low donor-specific MLR versus HLA-DR compatibility on kidney graft survival.

We have analyzed the predictive value on cadaver kidney graft survival of a low stabilized relative response (SRR) in donor-specific mixed lymphocyte culture (MLC). Thirty-eight recipients and donors of cadaver kidneys constituted the case material. The 12-month survival of cadaveric grafts was 83% when the SRR values of the mixed lymphocyte reaction (MLR) between recipient and donor were below or equal to 50 and 40% when the SRR values were above 50. The difference was statistically significant (P less than 0.006). A higher (though not significantly so) graft survival rate was obtained in transplant groups when the recipients and donors were well matched for DR antigens. The 12-month survival was 70% when no DR incompatibilities could be demonstrated and 50% when one or more DR antigens were incompatible. The primary role of MLR matching for the outcome of kidney graft survival is supported by the observation that the influence of the MLR is still significant when stratified for DR matching (P less than 0.05). In conclusion, when adequately stabilized, the specific MLC reactivity of the recipient against the donor is a very important predictive factor for the outcome of cadaver kidney transplantation, which stresses the importance of improvements in serological DR typing.

Cytotoxicity Tests, Immunologic↗
PubMed1985

HLA-B27 in juvenile chronic arthritis.

The prevalence of HLA-B27 in 88 patients with juvenile chronic arthritis was 22/88 (25%) with little variation among the 3 commonly recognized onset types. This was significantly more frequent than the prevalence of 9.4% in a Danish reference population. A strong association was found between the HLA-B27 antigen and 3 subgroups of patients: (1) boys with pauciarticular and late onset disease; (2) girls with apophyseal joint fusion; (3) a group of patients in whom the clinical picture was compatible with reactive arthritis or incomplete Reiter's syndrome. When these 3 subgroups were excluded from the total patient population, only 8 of the remaining 63 patients carried the B27 antigen, i.e., 13%, which was not significantly different from the prevalence in the reference population. Thus, the 3 subgroups account completely for the increase of B27 in the entire group of patients.

Adolescent↗
PubMed1984

Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients.

Secondary acute nonlymphocytic leukemia or its earlier stages, preleukemia or an acute myeloproliferative syndrome with refractory cytopenia and clonal cytogenetic abnormalities of the bone marrow, was diagnosed in 55 patients previously treated for other malignant diseases. In patients with overt leukemia, cytologic, and cytochemical studies showed predominance of the French-American-British (FAB) type M2. Cytogenetic examination demonstrated a normal karyotype in 11 cases, whereas clonal abnormalities were observed in 44 patients. Defects of chromosome 7 were observed in 24 cases, most often -7, and defects of chromosome 5 in 14 cases, most often 5q-. In addition, chromosomes 3 and 17 were possibly nonrandomly involved. Other abnormalities commonly observed in de novo acute nonlymphocytic leukemia as t(8;21) and t(15;17) were not observed and +8 rarely seen in secondary leukemia. The survival from the leukemic complication was short for the whole group of 55 patients (median, 7 months). However, a significantly longer survival was observed in a subgroup of 11 patients with a normal karyotype (P less than 0.01), due to a favorable response to antileukemic chemotherapy, and in a subgroup of 11 patients with -7 or -C as the only cytogenetic abnormality (P less than 0.01), due to a prolonged preleukemic phase, compared with the remaining 33 cases with mostly multiple karyotypic abnormalities. Three preleukemic patients with -7 who were studied during transformation to overt leukemia all developed additional cytogenetic abnormalities. According to the two-step or multistep hypothesis for malignant transformation, the prolonged preleukemic course in patients with -7 as the only abnormality could represent a premalignant stage, in which further evolution is required for development of overt leukemia. The patients showed a random distribution of blood groups and HLA types.

Acute Disease↗
PubMed1984

Postpartum autoimmune thyroid disorder associated with HLA-DR4?

Thirteen Danish women with postpartum thyroiditis were HLA-A, B, C and -DR typed. Nine of ten unrelated probands were DR4-positive which is significantly (corrected p = .01) different from the frequency (34.7%) of this antigen in unrelated controls.

Autoimmune Diseases↗
PubMed1984

Recurrent herpetic keratitis and HLA antigens.

A non-selected group of 50 patients with recurrent herpetic keratitis, subclassified into groups of stromal or epithelial forms was typed for HLA-ABC antigens. In none of the groups was a statistically significant association to a certain HLA antigen found. When these data are combined with other reviewed reports on HLA types in recurrent herpetic keratitis, a statistically significant association between HLA-B5 and the whole group of recurrent herpetic keratitis, as well as between the subgroup of recurrent stromal keratitis, could be demonstrated. Recurrent epithelial keratitis showed an insignificant association to this antigen.

HLA Antigens↗
PubMed1983

Transformation of LMTK- cells with purified HLA class I genes. II. Serologic characterization of HLA-A3 and CW3 molecules.

The expression of two different HLA class I genes was observed after transformation of LMTK- cells. The corresponding class I molecules reacted differentially with monomorphic monoclonal antibodies (m.Ab). Absorption and elution studies of the human alloantibodies reacting with the transformed cells and cellular radioimmunoassay of these cells with polymorphic m.Ab resulted in the identification of HLA-A3 and CW3 molecules. These transformed cells were used to immunize C3H mice and induce the production of xenogeneic antisera, which, following absorption, showed polymorphic reactivity with human cells, suggesting that some of these sera could be used as typing reagents.

Animals↗
PubMed1983

Detection of HLA-D/DR-related DNA polymorphism in HLA-D homozygous typing cells.

Sequences of different sizes are generated when DNA from homozygous HLA-Dw/DR typing cells are digested with restriction endonuclease and analyzed by hybridization with a HLA-D region class II antigen beta-chain cDNA probe. The patterns of hybridization were highly polymorphic but one endonuclease, BamHI, defined sequences unique to all HLA-Dw/DR specificities 1-8 except HLA-Dw/DR 2 and 6; however, these two specificities were resolved with the enzyme EcoRI. Digestion with other endonucleases such as Pst I results in patterns of restriction fragments that differ between homozygous typing cells of the same HLA-Dw/DR specificity. HLA-D region beta-chain probes permit HLA-D region genotyping at the DNA level and may allow detection of genes controlling the association of HLA specificities with a wide variety of diseases.

DNA↗
PubMed1983

Intra HLA-D/DR region recombinant detected by primed lymphocyte typing (PLT).

The chromosome 6 markers, HLA-ABC, D, DR, MT, properdin factor Bf, and complement factors 2 (C2) and 5 (C4), were studied in three families, each of which included two HLA identical siblings, one or both of whom were known to be HLA-B: GLO recombinants. The families were also typed with primed lymphocyte typing (PLT) for HLA-D/DR region associated DP antigens. None of these studies gave evidence that the recombinations had occurred within the HLA region. Mixed leucocyte culture (MLC) tests within the families showed no detectable stimulation between the HLA identical siblings in two of the families, but a very weak stimulation between the HLA identical siblings (H and G) in the third family (GG). No reactive PLT reagents were generated when cells from the HLA identical siblings of the first two families were primed against each other. In contrast, priming between cells of H and G gave rise to reactive reagents. One of these (GHx), reacted with a determinant which segregated within the GG family as if child G was a paternal recombinant between the HLA-D, DR, DP, and C4 loci, on the one hand, and on the other hand one or more loci governing other HLA-D/DR region controlled lymphocyte activating determinants. This reagent was only restimulated by cells from two of 47 unrelated individuals. The other PLT reagent (HGx) did not give a clearcut pattern within the family because it was weakly positive with all family members (most of whom were D/DR2-positive) except the specific responder; in the panel it reacted with a determinant significantly associated with D/DR/DP2. Other PLT reagents could be generated within the family against lymphocyte activating determinants controlled by genes in the two paternal haplotypes telomeric to the assumed recombinational site. These reagents gave stronger reactions than the HGx and GHx reagents and reacted with two determinants in the unrelated panel strongly associated with D/DR/DP2 and D/DR/DP6, respectively. It seems likely that the GG family represents a third example of a recombination between the HLA-DR and SB loci. Our findings further support the assumption that the DR determinants may be immunodominant in lymphocyte activation.

Chromosomes, Human, 6-12 and X↗
PubMed1983

HLA and disease 1982--a survey.

Within the last 7 years, HLA and disease studies have made it clear that most of the diseases previously known to be HLA-A- or B-associated do in fact show stronger associations with HLA-D/DR antigens. This observation strengthens the assumption that Ir and/or Is determinants are responsible for these associations in agreement with the fact that many of these diseases are characterized by autoimmune phenomena. However, some diseases, ankylosing spondylitis in particular, still show stronger associations with HLA-ABC than with DR antigens. Among the conditions which have been shown to be HLA-associated more recently, four deserves special mention: (i) maternal immunization against the Zwa antigen because this is a good candidate for an antigen-specific Ir gene action; (ii) IgA deficiency in blood donors because this is a non-antigen-specific immunodeficiency; (iii) idiopathic hemochromatosis and (iv) congenital adrenal hyperplasia due to 21-OH deficiency because immune mechanisms are unlikely to be involved. HLA studies and new genetic methodology have significantly advanced our knowledge about the inheritance of some diseases. Thus, HLA-B27 or a B27-associated HLA factor confers a dominant susceptibility to ankylosing spondylitis. HLA plays a definite and strong role in the susceptibility to IDDM, but simple genetic models (dominant, recessive, and intermediate) have been made unlikely on the basis of HLA results; the hypothesis that there are two different susceptibility genes within the HLA system still remains viable, but the demonstration of clinical heterogeneity and/or (better) of different pathogenetic pathways for DR3- and DR4-associated IDDM is required to substantiate it.

Cerebellar Ataxia↗
PubMed1983

HLA studies in chronic dermatophytosis caused by Trichophyton rubrum.

The HLA-ABC antigens were investigated in 34 and DR antigens in 28 patients with chronic dermatophytosis caused by Trichophyton rubrum. The distribution of the antigens did not differ from that of the controls. Abnormal immune response may be of importance in the susceptibility to chronic dermatophytosis, but HLA-controlled immune mechanisms seem unlikely.

Chronic Disease↗