The Respiratory Burst and Psoriasis

Psoriasis is a disease affecting about 1–2% of the population worldwide, similar to diabetes mellitus.1 It occurs somewhat more frequently in the white population than among Asians and Eskimos.1 The disease has two peaks of onset, an early one occurring around the age of 20 and a later one around 60.2 In early-onset psoriasis, 85% of patients exhibit the HLA Cw6 antigen; in the late-onset group, no such pattern of inheritance can be found.2

TNFα Primes Polymorphonuclear Leukocytes for an Enhanced Respiratory Burst to a Similar Extent As Bacterial Lipopolysaccharide

We examined whether preincubating polymorphonuclear leukocytes (PMN) with TNF alpha would result in an enhanced respiratory burst upon subsequent stimulation by various agents. Bacterial lipopolysaccharide (LPS), a known primer of PMN, was used as control. We found that both LPS (0.01 to 10.0 microgram/ml) and recombinant TNF alpha (0.001 to 1.0 microgram/ml) act as direct stimulants of PMN as measured by chemiluminescence. Sixty minutes of preincubation of PMN with 1 microgram/ml TNF alpha or 10 micrograms/ml LPS resulted in similar priming for the respiratory burst elicited by opsonized zymosan, phorbol myristate acetate, zymosan, zymosan-activated serum, aggregated immunoglobulin, and f-…

A Highly Decreased Binding of Cyclic Adenosine Monophosphate to Protein Kinase A in Erythrocyte Membranes is Specific for Active Psoriasis

A cyclic adenosine monophosphate binding abnormality in psoriatic erythrocytes that could be corrected by retinoid treatment has been reported. It was tested whether this binding abnormality is specific for psoriasis and the effects of treatment were compared with etretinate, cyclosporine A, or anthralin on 2-(3)H-8-N(3)-cyclic adenosine monophosphate binding to the regulatory subunit of protein kinase A in erythrocyte membranes. One hundred and fifteen individuals were evaluated, including: (i) 34 healthy persons; (ii) 15 patients with nonatopic inflammatory skin diseases (eczema, erythroderma, tinea, Grover's disease, erysipelas, urticaria); (iii) eight with other dermatoses mediated by i…

TAP-polymorphisms in juvenile onset psoriasis and psoriatic arthritis.

Abstract Juvenile onset psoriasis is strongly associated with the HLA-class I genes Cw6 and B57 whereas patients with psoriatic arthritis show an increased frequency of HLA-B27. It is unclear whether additional major histocompatibility genes also increase disease susceptibility. The TAP genes (transporter associated with antigen processing) encode two membrane-spanning proteins that translocate antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 60 patients with juvenile onset psoriasis, 63 psoriatic arthritis patients, and 101 caucasoid controls revealed an increase of the TAP1 ∗ 0101 allele in the psoriasis group, that could not be explained by linkage to o…

Effects of hydrazyl group containing drugs on leucocyte functions: an immunoregulatory model for the hydralazine-induced lupus-like syndrome.

Isoniazid (INH) and hydralazine (HYD) are transglutaminase (TGase, E.C.2.3.2.13.) substrates containing catalytically recruitable hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied. Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 microM, while that of INH was above 120 microM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 microM, INH was inhibitory only above 5000 micro…

Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor alpha, infliximab.

Abstract Background: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment. Objective: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions. Methods: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3…

Successful Extubation With Use of C1 Esterase Inhibitor Concentrate in a Patient With Hereditary Angioedema: In Response

Human Epidermal Langerhans Cells Replenish Skin Xenografts and Are Depleted by Alloreactive T Cells In Vivo

Abstract Epidermal Langerhans cells (LC) are potent APCs surveying the skin. They are crucial regulators of T cell activation in the context of inflammatory skin disease and graft-versus-host disease (GVHD). In contrast to other dendritic cell subtypes, murine LC are able to reconstitute after local depletion without the need of peripheral blood-derived precursors. In this study, we introduce an experimental model of human skin grafted to NOD-SCID IL2Rγnull mice. In this model, we demonstrate that xenografting leads to the transient loss of LC from the human skin grafts. Despite the lack of a human hematopoietic system, human LC repopulated the xenografts 6 to 9 wk after transplantation. By…

Transglutaminase and polyamine dependence of effector functions of human immunocompetent cells

AbstractThe effects of the transglutaminase inhibitor dansyl cadaverine (DC) and the polyamine antagonist methyl glyoxal-bis-(guanylhydrazone) (MeGbG) on the response of lymphocytes towards allogeneic and lectin stimulation and on the zymosan-induced chemiluminescence of neutrophilic granulocytes was studied. Application of DC resulted in dose-dependent suppression of chemiluminiscence and lymphocyte proliferation; no difference of inhibitory potential occurred with variation of incubation time in the latter system. MeGbG was inactive in granulocytes, but inhibited lymphocyte proliferation; its effect increased with time. The experiments provide further evidence for the importance of transg…

Asphyxiation by laryngeal edema in patients with hereditary angioedema.

Objective To describe the occurrence of fatal laryngeal edema in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Patients and Methods We describe 6 patients from various regions of Germany who died from laryngeal edema within the last 10 years. Furthermore, we conducted a retrospective survey of 58 patients with hereditary angioedema, originating from 46 affected families. The data were obtained from the attending physicians and from the patients' relatives. Results Among the 6 reported patients, aged 9 to 78 years, hereditary angioedema had been diagnosed in 3 and was undiagnosed in 3. None of them had an emergency cricothyrotomy or received C1 inhibitor concen…

Stimulus-Dependent Increased Generation of Oxygen Intermediates in Monocytes and Polymorphonuclear Leukocytes in Psoriasis

Based on recent findings indicating increased respiratory burst activity of monocytes (M phi) and polymorphonuclear leukocytes (PMN) in psoriasis upon stimulation with zymosan particles, we examined the question of whether incubation with various stimuli always results in augmented oxidative metabolism in psoriatic phagocytes. We compared M phi and PMN isolated from the peripheral blood of 12 patients with psoriasis and 12 control individuals. We measured the generation of oxygen intermediates of resting and stimulated M phi and PMN by luminol-enhanced chemiluminescence. The stimulants applied were: (1) aggregated immunoglobulin (aggIg), (2) zymosan, (3) zymosan opsonized with autologous se…

398 Safety of 62-week treatment of psoriasis with cyclosporine

170 Psoriatic arthritis: Predisposing, constitutive and provoking factors

396 Ciclosporine therapy for psoriasis leading to fathering of a healthy child in a previously infertile male

PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders

Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing–remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after …