Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor Vfi repertoire using monoclonal antibodies against 10 different V8 families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of Vfi2+ T cells (P < 0.05). The expansion of V.82+ T cells occurred in both the CD4+ and the CD8+ T cell subsets.Sequence analysis of T cell receptor chain genes of V/32-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked Vj32+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s). (J. Clin. Invest. 1995. 96:2106-2112
Objective. To test the hypothesis that during exacerbations of systemic lupus erythematosus (SLE), endothelial cells are activated to increase their expression of adhesion molecules.Methods. Endothelial cell expression of E-selectin, vascular cell adhesion molecule 1 (VCAM-l), and intercellular adhesion molecule 1 (ICAM-1) was quantitated immunohistochemically in 20 biopsy specimens from nonlesional, non-sun-exposed skin from 16 SLE patients. Disease activity was evaluated with the SLE Disease Activity Index (SLEDAI) and with measurements of complement components C3a desArg, C3, and C4.Results. The mean expression of all 3 adhesion molecules was significantly elevated in patients with SLE versus healthy controls, as well as in patients with active versus inactive SLE. The mean C3a desArg level was significantly higher in patients with active SLE compared with those with inactive SLE. The SLEDAI scores correlated directly with C3a desArg levels and inversely with C3 and with C4 levels. Evaluation of serial biopsy specimens demonstrated loss of endothelial cell adhesion molecules and reduction of C3a levels with clinical improvement .
Objective. To investigate whether systemic lupus erythematosus (SLE) is accompanied by increased serum nitrite levels, whether active compared with inactive disease is associated with greater nitric oxide (NO) production, and whether endothelial cells or keratinocytes serve as cellular sources of NO by virtue of their increased expression of either constitutive nitric oxide synthase (cNOS) or inducible NOS (iNOS).Methods. Fifty-one serum samples (46 from patients with SLE) were analyzed for NO production by measuring nitrite levels in a calorimetric assay. Skin biopsy samples from 21 SLE patients and 11 healthy volunteers were evaluated immunohistochemically, using monoclonal antibodies, for endothelial cell and keratinocyte cNOS and iNOS expression.Results. Serum nitrite levels were significantly elevated in the 46 patients with SLE (mean & SEM 37 & 6 pM/liter) compared with controls (15 & 7 pM/liter; P < 0.01), and were eleyated in patients with active SLE compared with those with inactive disease (46 2 7 pM/liter versus 30 e 7 pM/liter; P < 0.01). Serum nitrite levels correlated with disease activity (r = 0.47, P = 0.04) and with levels of antibodies to doublestranded DNA (r = 0.35, P = 0.02). Endothelial cell expression of iNOS in SLE patients (mean & SEM score 1.5 e 0.2) was significantly greater compared with controls (0.6 e 0.2; P < 0.01), and higher in patients €1.
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