Wieslaw Glinski

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 Bowens 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.

Cell-Mediated Immunity in Epidermodysplasia verruciformis

Investigations were performed in 6 cases of epidermodysplasia verruciformis and 2 healthy family members. Nonspecific cell-mediated immunity (CMI) was studied by measuring response to phytohemagglutinin (PHA) and concanavalin A (Con A), percentrages of E- and EAC-rosette-forming lymphocytes, bacterial skin tests, and allergic reactions to dinitrochloro-benzene (DNCB). Impairment of CMI was manifested by reduction in the percentage of E rosettes, and lowered response to PHA, and- to a lesser degree- to Con A. The immune response to DNCB sensitization was invariably negative. Impairment of CMI was greater in cases of long duration and with extensive lesions. The cases of similar duration and extent of lesions, which never showed tendency to tumor formation, were not different in CMI in comparison with cases with numerous tumors. Only in cases with very advanced tumors CMI was impaired parallel to the gravity of the patients general condition.

NEUROPEPTIDES IN PSORIASIS: POSSIBLE ROLE OF BETA-ENDORPHIN IN THE PATHOMECHANISM OF THE DISEASE

Background. An increased concentration of neuropeptides in psoriatic lesional skin may be responsible for alterations in the neurogenic erythematous response and transmission of stimuli through sensory nerve fibers (sensation of pruritus).

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.

Continuous peritoneal dialysis for treatment of psoriasis

Psoriatic lesions were found to disappear spontaneously under haemodialysis [1 4] or continuous peritoneal dialysis [5] without any additional topical application of tar and corticosteroids, and/or systemic treatment with cytostatic drugs. Since both procedures recently introduced for therapy of psoriasis did not interfere directly with the excessive epidermal cell proliferation, a characteristic feature of the disease, the mechanism of the clearing of psoriatic lesions, remains completely unknown. Some hypotheses were raised such as removal of an noxious substance probably of epidermal origin which may be filtered by the normal kidney, but not excreted owing to tubular reabsorption in psoriasis [5], as well as immunological activation, inactivation of substances, or alteration of feedback systems [4]. Taking into consideration that lymphocytes and polymorphonuclear leucocytes [PMNL] may play an important rote in the pathogenesis of psoriasis, we decided to explore an alternative hypothesis that not elimination of low molecular dialysable factor, but removal of white blood cells with dialysate could be reponsible for the clearing of psoriasis. Lymphocytes and PMNL are known to form infiltrates in psoriatic lesions [ 6 7]. Furthermore, they could be a carrier of immunological factors, such as immune complexes, rheumatoid-like factors, anti-basal cell nuclei autoantibodies, or other immunoglobulins, and complement [8-9]. Complement activation products generated after binding of stratum corneum (SC) antigens with circulating anti-SC autoantibodies [t0] are presumed to exert chemotactic activity on PMNL which penetrate into the horny layer-forming Munro microabscesses [11]. Abnormalities of T-lymphocyte function were also reported [12]. The purpose of our paper was to determine : (1) whether white blood cells are removed by continuous peritoneal dialysis in a significant number, (2) whether some immunological factors related to these cells are eliminated on their surface

Basement membrane zone as a target for human neutrophil elastase in psoriasis

SummaryHuman neutrophil elastase was found, by indirect immunofluorescence using rabbit anti-elastase antiserum, to be bound to basement membrane of psoriatic plaques in vivo. The enzyme was also identified inside the migrating neutrophils in the reticular dermis and dermal papillae, as well as outside the cells in micro-abscesses in psoriatic skin. In vitro incubation of normal skin with human neutrophil elastase resulted in the destruction of hemidesmosomes and separation of the epidermis from the dermis above localizations of bullous pemphigoid antigen. These findings are direct evidence that human neutrophil elastase could play a role in psoriasis in in vivo destruction of the epidermal — dermal junction.

Alpha1-proteinase inhibitor in psoriasis: reduced activity in symptom-free patients and during flare

SummaryThe aim of this study was to quantitate the active fraction of the α1-proteinase inhibitor (α1-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. Alpha1-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 α1-PI was stimulated during the appearance of active psoriatic lesions, but to a much lesser degree in patients with early onset (≤21 years) than in patients with late onset of psoriasis (>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-α1-PI system in psoriasis is abnormal and this may contribute to the pathogenesis of the disease. The decreased α1-PI during flare may be responsible for the disease activity, at least in patient with early onset of psoriasis.

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

SummaryTen 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.

Excessive costimulation of CD3-dependent lymphocyte response by extracellular matrix proteins in severe widespread psoriasis

Costimulation of anti-CD3-triggered proliferative T-cell responses by type I and type IV collagen and fibronectin was studied in 25 patients with psoriasis and 12 healthy subjects. The stimulation index of anti-CD3-mediated responses in the presence of type I collagen was about half that in the controls. Although the CD3-dependent proliferative response of psoriatic lymphocytes in patients with active widespread plaque psoriasis was reduced by about 50%, costimulatory responses induced by type IV collagen and fibronectin were found to be enhanced in relation to the controls. The degree of costimulation by type IV collagen and fibronectin was related to disease severity. The highest values of the stimulation index were found in patients with a PASI greater than 24, skin involvement of more than 40% of body surface area, and a duration of psoriatic lesions of more than 3 months. The results indicated that in active widespread plaque psoriasis subpopulations of T cells bearing receptors for some extracellular matrix proteins were increased in the peripheral blood. A factor responsible for this phenomenon may be trafficking of T cells through the basement membrane zone of psoriatic lesions, which presumably causes modification of T cell immunological responsiveness after recirculation.

Decreased specific anti-elastase activity in the uninvolved skin of patients with psoriasis

SummaryInhibitory activities against elastase, chymotrypsin and trypsin were studied in the fluid from experimentally developed suction blisters in the uninvolved skin of patients with psoriasis. These activities determined by spectrophotometry of specific synthetic low molecular weight substrates were compared with respective antiproteinase activities in sera of 32 patients with psoriatic lesions, ten patients in remission, and ten healthy volunteers. A marked reduction (29.2%) in the specific elastase inhibitory activity of blister fluid was found in patients with psoriasis when compared with normal subjects (p<0.05), since neither chymotrypsin nor trypsin inhibitory activities were altered. This reduction was despite about a 30% increase in the elastase inhibitory activity in the sera of these patients, which was related presumably to their increased activity of α1-proteinase inhibitor, the main serum antiserine proteinase inhibitor. A decreased blister fluid∶serum elastase inhibition ratio was shown in a large majority of patients with psoriasis, even in symptomless patients. The deficiency in specific elastase inhibitory activity of suction blister fluid was predominantly associated with early onset of psoriasis, guttate lesions and inactive lesions, skin involvement less than 20% of body surface, duration of relapse shorter than 2 months, and frequent relapses. These data indicate that the uninvolved skin of patients with psoriasis contains low concentrations of specific elastase tissue inhibitor, which deficiency might result in an excessive in vivo hydrolytic activity of neutrophil elastase released from migrating cells in the psoriatic skin.