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Biomedical subjects

W Gliński

Publications and source records attributed to W Gliński.

At least 19 recordsLinked to original sources

Alterations of T-cell: extracellular matrix proteins interactions in psoriasis.

Recent data indicate that extracellular matrix proteins (collagens, fibronectin) co-stimulate T-cell lymphoproliferative responses in vitro. We have studied the co-stimulatory activities of those proteins in patients with psoriasis, a disease in which T cells infiltrating the skin are continuously exposed to collagen and fibronectin. CD3-triggered T-cell proliferative responses were lower in psoriasis but could be enhanced by collagens I and IV and fibronectin. Interestingly, collagen-I-dependent co-stimulation was markedly decreased in patients with psoriasis, while there was a trend towards the enhancement of collagen-IV-induced responses. Those disturbances were most frequently seen in patients with active and widespread lesions. It appears that abnormalities of extracellular matrix protein-derived signals could play a role in the immunopathology of psoriasis.

Adult↗

Alpha 1-proteinase inhibitor in psoriasis: reduced activity in symptom-free patients and during flare.

The aim of this study was to quantitate the active fraction of the alpha 1-proteinase inhibitor (alpha 1-PI) in psoriasis. Serum proteinase inhibitory capacity was measured vs porcine pancreatic elastase of a known active fraction against its specific substrate (Suc-Ala3-pNA). The inhibitory capacity was determined in 21 symptom-free patients, 134 patients with skin lesions, and 23 healthy volunteers. Alpha 1-PI was found to be significantly decreased in symptom-free patients and in those with stationary lesions, in a manner similar to the reduced activity of neutrophil proteinases, elastase, and cathepsin G. The synthesis of alpha 1-PI was stimulated during the appearance of active psoriatic lesions, but to a much lesser degree in patients with early onset (less than or equal to 21 years) than in patients with late onset of psoriasis (greater than 21 years). The early onset subgroup differed by a more frequent familial occurrence of psoriasis and a more severe course of the disease. The data indicate that the regulation of the proteinase-alpha 1-PI system in psoriasis is abnormal and this may contribute to the pathogenesis of the disease. The decreased alpha 1-PI during flare may be responsible for the disease activity, at least in patients with early onset of psoriasis.

Adolescent↗

Leukopheresis for treatment of psoriasis: is therapeutical benefit related to reduced activities of neutral proteinases of polymorphonuclear leukocytes?

Ten patients were treated with repeated leukophereses performed one to three times per week for 2-5 weeks. Two of the patients was cleared completely, four exhibited regression of more than one-half of the lesions, and four showed only a slight improvement. The therapy did not markedly affect the granulocyte count in peripheral blood, and the beneficial clinical response was not related to the number of polymorphonuclear leukocytes (PMNs) removed by leukophereses. During therapy, the activities of elastase, cathepsin G, lysozyme, and myeloperoxidase in PMNs were determined by spectrophotometry. PMNs isolated using a Haemonetics 30 blood-cell separator were about 50% deficient in these activities in comparison to cells obtained directly from peripheral blood. Thus, leukopheresis induces a marked degranulation of PMNs. Repeated leukophereses were found to generate significant variations in the activities of circulating PMN granule enzymes and in the levels of acid-soluble proteins. Remission or great improvement were observed in patients who, during therapy, exhibited decreased PMN elastase and cathepsin G activities, whereas a poor clinical response was accompanied by high enzymatic activities.

Adult↗

Identification of HLA antigens in familial and non-familial epidermodysplasia verruciformis.

The distribution of HLA specificities was studied in 7 non-familial cases of epidermodysplasia verruciformis (EV) and in 5 cases from one family. In the non-familial cases, six antigens of locus A (2, 3, 9, 10, 24, 26) and eight antigens of locus B (7, 15, 27, 35, 37, 38, 40, 41) were found. All 5 cases of familial EV possessed 26,5 haplotype, however, 6 of the remaining 12 healthy family members inherited the same haplotype. There is no association of EV with HLA-A and B antigens. However, the defect of cell-mediated immunity, present in all EV cases, may indicate the association of the disease with other major histocompatibility products (i.e. loci on immune response genes).

Animals↗

Neutral proteinases and other neutrophil enzymes in psoriasis, and their relation to disease activity.

The activities of elastase, cathepsin G, lysozyme and myeloperoxidase of polymorphonuclear leukocytes were determined by spectrophotometry in thirty-six patients with psoriatic lesions, twelve symptom-free patients with psoriasis and fifteen normal controls. The mean activities of cathepsin G, elastase and lysozyme were found to be increased by 55 to 70% in patients with actively spreading plaque lesions compared with healthy controls (P less than 0.01). Most patients with guttate lesions had total enzyme activities within the normal range. Those with stationary plaque psoriasis had activities of both neutral proteinases (cathepsin G and elastase) which were about 40% lower than normal controls (P less than 0.05). In the lesion-free psoriatics, the activities of neutral proteinases were about 70% of control values. Our findings emphasize the importance of assessment of disease activity in this sort of investigation. The present data may help to resolve much of the confusion regarding PMN function in psoriasis.

Cathepsin G↗

T cell defect in patients with epidermodysplasia verruciformis due to human papillomavirus type 3 and 5.

Most of the patients with epidermodysplasia verruciformis (EV) were anergic to sensitization to dinitrochlorobenzene (DNCB) and were shown to have a decreased number of T lymphocytes and reduced lymphocyte PHA responsiveness. Preserved cell-mediated immunity (CMI) was found only in the abortive cases of EV infected with human papillomavirus type 3 (HPV-3). CMI was impaired to the same extent in patients with EV induced by HPV-3 and HPV-5, and in EV cases with combined infection with both viruses. In contrast to this, malignant transformation, i.e. of Bowen's carcinoma type, was observed only in the 7 patients infected with HPV-5. This could indicate that malignancy in EV is related rather to the oncogenic potential of HPV-5 type than to the extent of T cell defect that was similar in both EV varieties due to HPV-3 and HPV-5.

Animals↗

Comparative studies on cell-mediated immunity in patients with different warts.

The distribution of peripheral blood T and B lymphocytes, the in vitro lymphocyte response to PHA, and in vivo experimental DNCB sensitization were studied in patients with different clinical forms of warts (common, 84; flat, 88; plantar, 22; genital, 14) and in 15 cases of epidermodysplasia verruciformis (EV). The percentage of T lymphocytes forming E rosettes was significantly decreased in patients with common (54.8%), flat (47.5%) and plantar (58.3%) warts, and those with EV (47.6%) in comparison with normal controls (68.4%). The DNCB sensitivity developed less frequently and it was less intensive in patients with common and flat warts than in the normal population. 60% of EV cases were anergic to challenging doses of DNCB. The lymphocyte response to PHA was reduced in all groups of patients studied as compared to normals. T cell function was found to be most defective in patients with EV and those with flat warts. Only a slight but statistically significant defect was demonstrated in the common wart group. CMI in patients with both plantar and genital warts was shown to be almost normal; except minor alterations of PHA-induced lymphocyte transformation and E rosetting T lymphocyte counts. These data have shown the divergency of CMI defect in the patients with different clinical forms of warts caused by various HPV types. This could indicate that distinct HPV types varied in their infectiveness and host cell-mediated resistance is a fundamental factor preventing viral infection.

Humans↗

Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis.

21 years of follow-up study of a family with epidermodysplasia verruciformis (e.v.) have shown that members of one family can be infected with different human papillomaviruses (HPVs), either HPV 3 or HPV 4, and sometimes with both. The clinical picture resembled disseminated flat warts in cases induced by HPV 3, whereas in those caused by HPV 4 there were flat red or red-brownish plaques and depigmented pityriasis versicolor-like lesions. Malignancies developed only in family members infected with HPV 4, whereas the cases due to HPV 3 ran a more benign and slowly progressive or stationary course. There were also abortive and regressive cases, and the 3 children in whom the wart-like lesions did not recur after removal had an unimpaired cell-mediated immunity (CMI). In all cases of e.v., irrespective of the inducing virus, CMI was low, which seems to be an important factor in the pathogenesis of the disease. Humoral antibodies directed specifically against HPV 3 were present in the majority of the cases, mainly those infected with HPV 3.

Adolescent↗

[Is psoriasis an autoimmunologic disease?].

DThe defective function of T-lymphocytes, which is a finding in active psoriasis, is transitional and reversible, whereas the immunological mechanism is mainly related to the formation of immune complexes consisting of stratum corneum antibodies and stratum corneum antigen, which through binding of complement and activation of chemotactic complement components is responsible for the phenomenon of "squirting papillae". The earliest lesions preceding pin point papules, called pre-pin-point papules, were induced by stripping or developed spontaneously in a marked field closely observed for several days. In the changes preceding earliest psoriatic lesions. Abundant polymorphonuclear infiltrates are present, and polymorphs seem to play an important role in a selfperpetuating of disease process. The therapeutic implications of the immunologic studies in psoriasis are: either depletion of activated polymorphs (eg. continuous peritoneal dialysis) and/or removal of the factors responsible for their activation (eg. treatment of focal infections) or external use of the drugs affecting the antigenicity of stratum corneum (tars), or inhibition of exocytosis (a probable mechanism of puva).

Autoimmune Diseases↗

Cell-mediated immunity (CMI) in psoriasis.

Patients with psoriasis were found to have less intensive experimental DNCB sensitization and decreased lymphocyte response to nonspecific mitogens, PHA, Con A, and PWM. E rosette formation was defective only in active psoriasis, in contrast to normal T and B cell counts. A reduction in DNCB hypersensitivity development and the percentage of E rosette forming lymphocytes were related to disease activity, but not to extention of skin lesions. The defect of E rosette function appeared to be transitional and completely disappeared in the remission. Abnormalities in CMI in psoriasis were found to be related at least partially to the existence in patients sera of a factor inhibiting normal T lymphocyte function. The study provides no evidence for the presence of primary CMI defect in psoriasis.

B-Lymphocytes↗

Immunologic abnormalities in psoriasis: the inhibition of leucocyte migration by stratum corneum antigens.

The migration inhibition of peripheral blood leucocytes by stratum corneum (SC) antigens extracted from psoriatic scales and normal skin was studied in 25 patients with psoriasis and 12 normal controls. In 44% of patients, the radius of the area of spontaneous migration in the absence of antigen was significantly reduced. 9 out of 25 psoriatic cases showed inhibition of leucocyte migration after the addition of both SC antigens. Migration inhibition with SC antigens was observed only in patients in whom the radius of spontaneous migration area appeared to be normal. The data did not confirm the evidence of delayed hypersensitivity to epidermal SC antigens in patients with psoriasis. The decrease of spontaneous leucocyte migration in psoriasis might be dependent on the influence of antibodies against stratum corneum and/or immune complexes coated on lymphocyte or leucocyte surface membrane.

Adolescent↗