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Biomedical subjects

H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 109 records · Page 6Linked to original sources

The effects of cyclosporin A on T lymphocyte and dendritic cell sub-populations in psoriasis.

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR+ CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Adult↗

Relation between bone erosions and rheumatoid factor isotypes.

Total rheumatoid factor (RF) activity and individual RF isotypes were measured in 62 patients with rheumatic diseases. Retrospective analysis of available x rays showed an association between IgA RF and the occurrence of periarticular bone erosions in hands. In contrast, IgG RF and IgM RF did not show any significant association with erosions. Furthermore, a close correlation was observed between the RF isotype levels in simultaneously drawn serum and synovial fluid samples. The possible significance of IgA RF in the pathogenesis of bone erosions is discussed.

Adolescent↗

Enzyme-linked immunosorbent assay (ELISA) screening test for detection of rheumatoid factor.

A new enzyme-linked immunosorbent assay (ELISA) screening test for total rheumatoid factor (RF) activity is described. Rabbit IgG was used as antigen and enzyme-conjugated monoclonal anti-kappa antibody as third layer. Of 183 samples measured for RF isotype levels, 60 were found to have one or more raised. In terms of raised isotypes the ELISA screening test had a sensitivity of 97% (58/60) while the Rheumaton had a sensitivity of only 75% (45/60). Nearly all discordant false-negative samples had only one RF isotype raised. The ELISA test gave 29% (53/183) and the Rheumaton 34% (63/183) false-positive results. Thus the ELISA test was more specific and sensitive for the detection of raised single RF isotypes than the Rheumaton and Rose-Waaler tests. Moreover, approximately 30% of RA patients were seronegative according to the conventional RF tests but only 8% in the new ELISA system.

Enzyme-Linked Immunosorbent Assay↗

Monocytosis and monocytic infiltration of decidua in early pregnancy.

This study showed a marked increase of blood monocytes in the 7th-20th week of pregnancy. The highest monocyte values were observed in the very first weeks whereas neutrophil counts were increasing throughout the observation period. No significant pregnancy associated changes were found in T-cell subpopulations or in HLA-DR expression by monocytes. First trimester decidual tissue contained many HLA-DR, Leu-M3 positive cells. Their distribution was patchy and mainly confined to areas of prominent decidual reaction. In contrast normal secretory phase endometrium showed only occasional Leu-M3, HLA-DR positive cells but a few clusters of glandular epithelial cells expressed HLA-DR. Culture supernatants from both decidual and secretory endometrial tissues contained PGE2 in concentrations known to suppress PHA lymphocyte responses in vitro. We postulate that monocytes infiltrating the decidual tissue may, possibly through PGE2 mediated immunosuppression, help to prevent rejection of the fetal allograft early in pregnancy.

Antigens, Surface↗

Further evidence for the procidin function of C3.

It was found that heat-inactivated serum supported phagocytosis, but did not promote oxygen consumption or killing of Candida, by human polymorphonuclear leucocytes (PMNs). It was also established that C3 is required for activation of the PMN candidacidal related mechanisms of superoxide anion generation and iodination. Addition of purified C3 to C3 deficient serum restored phagocytic killing. Further evidence for C3 involvement in Candida killing was obtained from studies of PMN ingestion and killing in the presence of trypan blue or heparin. Trypan blue, which antagonises C3 receptors, prevented efficient killing, as did heparin, which affects C3 conversion in normal serum. From these results it is evident that phagocytic killing is not an obligatory consequence of ingestion. The findings also indicate that killing by PMNs is dependent upon the interaction of humoral factors, termed procidins, with receptors responsible for initiation of microbicidal mechanisms. Activation products of C3 may stimulate phagocytic killing by engagement of their counterpart receptors on PMNs.

Candida albicans↗

The effect of indomethacin treatment on lymphocyte PHA reactivity in healthy controls and patients with lymphoma and sarcoidosis.

Lymphocytes from healthy volunteers who took indomethacin orally for 3 d showed an enhanced in vitro response to phytohaemagglutinin (PHA). When indomethacin was added in vitro, lymphocytes from healthy controls showed similar but more consistent increases of PHA responses than lymphocytes from patients with sarcoidosis or lymphoma. Moreover, the enhancing effect of indomethacin was by and large more pronounced in those patients who had relatively normal PHA lymphocyte responses in the absence of indomethacin, and the presence of indomethacin failed in most instances to increase subnormal responses to normal control levels. These findings are not consistent with the notion that increased prostaglandin synthesis is the principal cause of subnormal PHA reactivity of lymphocytes from patients with sarcoidosis or lymphoma.

Adolescent↗

The effects of topical treatment with steroids or dithranol on epidermal T lymphocytes and dendritic cells in psoriasis.

We describe the effects of treatment with topical steroids or dithranol on T and dendritic cells in the skin of patients with chronic plaque psoriasis. Resolution of lesions by both types of topical treatments was accompanied by a marked decrease in epidermal T cells. In steroid treated lesions there was also a reduction in DR+ dendritic cells to normal numbers during treatment and the rate of disappearance of both cell types correlated with the rate of resolution. However, a significant reduction of dendritic cells was not usually observed until after the T cells had almost disappeared from the epidermis and substantial healing of lesions had taken place. Dendritic cells in steroid-treated uninvolved skin had decreased to a lower level than in normal skin. In contrast, dithranol did not affect dendritic cells, either in lesional or in unaffected psoriatic epidermis. The decrease in dermal T cells observed with both treatments was more marked in steroid-treated lesions and correlated with resolution. However, blood T cells were unaffected by both treatments. The findings provide further support for the role of T cells in the pathogenesis of psoriasis.

Administration, Topical↗

Rheumatic diseases in an Icelandic family. Clinical and immunological survey.

We have studied 192 members of a highly inbred Icelandic family with clustering of rheumatic diseases. Twelve consanguineous marriages are known in the family and 54 of 65 surviving offsprings of these (inbred group) were traced. Thirty-nine family members were affected by rheumatic diseases; 18 of them belonged to the inbred group. Eleven of 20 family members with rheumatoid arthritis (RA) came from the same inbred group. Eleven of the inbred group had a positive Rose-Waaler test for rheumatoid factor (RF) and the inbred group had significantly higher serum levels of IgG and IgM than an age and sex matched group from the family. Serum IgM RF was significantly associated with the age of the family members, but IgA RF and IgG RF did not show any such association. The possible role of recessive genes in the rheumatic diseases, as well as the inbreeding effect regarding certain extended HLA-complotypes is discussed.

Adolescent↗

Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment.

The numbers and HLA-DR expression of T cell subsets and dendritic cells in chronic psoriatic plaques were compared to previously reported findings in spontaneously resolving guttate lesions, and the effects of PUVA treatment on these cell populations studied. The chronic lesions showed a similar T helper/T suppressor (TH/TS) ratio (0.66 +/- 0.10) to resolving guttate lesions. However, in contrast to the resolving lesions which do not contain activated epidermal TH cells, a substantial proportion of the TH cells in the persistent plaques were DR+. Moreover, these persistent lesions contained markedly increased numbers of DR+ dendritic cells, approximately 20% of which were T6 negative. PUVA-induced resolution of chronic lesions was associated with depletion of epidermal TH and TS cells, and a subsequent reduction in DR+ dendritic cells. In each patient the rate of disappearance of both cell types correlated with the rate of resolution. Furthermore, the epidermal T cell depletion preceded the onset of clinical improvement. In contrast, significant reduction of the dendritic cells was generally not observed until the lesions were largely resolved. Dendritic cells decreased faster in uninvolved than in lesional skin and to a subnormal level. Dermal T cells also decreased during PUVA therapy but this did not show any obvious correlation with resolution of the lesions. Blood T cell levels were not significantly affected by the treatment. These findings support the concept that the initiation and maintenance of the psoriatic process requires activation of TH cells in the epidermis via interaction with antigen presenting cells. Furthermore PUVA treatment may clear psoriasis by interfering with such a mechanism through its effects on T lymphocytes.

Adult↗

Antibody production in the brain tissue of mice immunized into the central nervous system.

Injection of T-dependent antigens into the subarachnoid space and brain parenchyma induced a marked antibody production in the spleen, as detected by plaque-forming cells (PFC). The presence of specific antibody-producing cells in the brain tissue was only observed in those animals which received antigenic challenge into the central nervous system. Local antibody production requires successive antigenic challenges with doses of sheep red blood cells larger than 2 X 10(4). Brain trauma did not influence the background numbers of spleen PFC nor did it induce the appearance of antibody-producing cells in the brains of mice challenged intra-peritoneally. The presence of specific antibody-producing cells in the brain tissue following antigenic challenge within the CNS suggests that a local immune response can be maintained in this organ.

Animals↗

Use of monoclonal antibodies and F(ab')2 enzyme conjugates in ELISA for IgM, IgA and IgG rheumatoid factors.

Enzyme-linked immunosorbent assays (ELISA) were developed for the measurement of rheumatoid factors (RF) of IgM, IgA and IgG isotypes. Rabbit IgG was used as substrate and the results expressed as units by referral to standards. Rabbit antibody could not be used for detection of IgA or IgG RF without either pepsin-digesting the antibody or inactivating the IgM RF activity of the test sample. When a double antibody system of mouse monoclonal anti-human Fab gamma and goat (Fab')2 anti-mouse IgG was used for the IgG RF assay, pepsin treatment of serum samples was unnecessary. Raised serum IgA RF may be a reliable early marker of erosive rheumatoid arthritis (RA).

Antibodies, Monoclonal↗

Unsuccessful induction of low-zone tolerance to bovine serum albumin injected into the subarachnoid space.

Introduction of T-dependent antigens into the subarachnoid space (isas) resulted in higher systemic antibody responses in mice than injections into the peritoneal cavity (ip) or other sites commonly used for immunization. Antibody production in isas immunized mice was not increased by treatment with cyclophosphamide (Cy) at doses known to abolish T-suppressor-cell activity, but such treatment increased antibody production in ip immunized mice toward the higher level which was observed in the isas immunized animals. Suppressor cell-dependent low zone tolerance (LZT) to TNP-BSA could not be induced by isas injections of deaggregated BSA (d-BSA). Conversely, mice which were unresponsive to ip injected d-BSA showed consistent systemic antibody responses when the antigen was injected isas. These observations indicate that immune responses initiated within the CNS are associated with relatively ineffective induction of systemic suppressor cell activity.

Animals↗

Epidermal T lymphocytes and HLA-DR expression in psoriasis.

Double staining immunofluorescent techniques and monoclonal antibodies were used to study the numbers, distribution, HLA-DR expression and relationship of T-cell subpopulations and dendritic cells in psoriatic skin. In the dermis there was a definite increase in both T helper and T suppressor cells in uninvolved skin of psoriatic patients, and the appearance of clinical lesions was not associated with any detectable change in the numbers of these cells in the dermis. In contrast, eruption of skin lesions was associated with an increase in the numbers of epidermal HLA-DR+ dendritic cells and also with epidermal influx and activation of T helper cells, while resolution of lesions coincided with increased epidermal entry and activation of T suppressor cells. Both the T helper and T suppressor cells were preferentially found adjacent to epidermal dendritic cells. These findings suggest that the clinical activity of psoriasis may be dependent upon the interaction of T helper and suppressor cells with antigen-presenting cells in the epidermis.

Antibodies, Monoclonal↗

T-cell subpopulations in the blood and skin of patients with psoriasis.

Monoclonal antibodies were used to determine, simultaneously, the proportions of T-cell populations in the peripheral blood and in the skin lesions of fifty-one patients with psoriasis. The results were analysed in relation to the extent, age and clinical type of the skin lesions. In the group of patients with extensive lesions, a significant reduction in the number of total T (TT) and T helper/inducer-cells, (TH), but not in T suppressor/cytotoxic cells (TS) was observed in the peripheral blood. Furthermore, the skin TH/TS ratio was greater in late guttate and in chronic plaque lesions than the corresponding ratio in the blood. These findings suggest that there is an active selective recruitment of TH cells into established psoriatic lesions. In contrast, the TH/TS ratio in early guttate lesions was the same as in the blood, and significantly lower than in the plaque lesions. An additional finding was a decrease of TS, and a corresponding increase of null cells in the blood of patients with chronic plaque psoriasis. These observations provide further evidence for the participation of T cells in the pathogenesis of psoriasis.

Antibodies, Monoclonal↗

Felty's syndrome associated with high levels of IgA rheumatoid factor.

A 64-year-old woman with rheumatoid arthritis developed Felty's syndrome. Her serum contained large amounts of IgA rheumatoid factor (RF) but insignificant levels of IgM-RF and IgG-RF. It is postulated that the high levels of IgA-RF may have contributed to the neutropenia.

Enzyme-Linked Immunosorbent Assay↗

Prospective study of early rheumatoid arthritis. I. Prognostic value of IgA rheumatoid factor.

Thirty-three patients with early arthritis, 28 of whom developed classical/definite rheumatoid arthritis (RA), were followed up for two to four years. Rheumatoid factor (RF) levels of the IgM, IgA, and IgG isotypes were measured in serum and synovial fluid by an ELISA technique developed in our laboratory. All seven patients who presented with raised IgA RF developed erosions of their hands and wrists. This was significantly different from the remaining 26. By contrast none of the five patients who presented with isolated elevation of IgM RF developed erosive disease. The patients with raised IgA RF needed significantly more treatment with 'specific' drugs than the remaining 26. It is suggested that the detection of IgA RF in early RA indicates poor prognosis, justifying a more aggressive treatment at an early stage.

Arthritis, Rheumatoid↗