Cytokine Pattern in Blister Fluid and Sera of Patients with Pemphigus

Baroni, Adone; Perfetto, Brunella; Ruocco, Eleonora; Greco, Rita; Criscuolo, Daniela; Ruocco, Vincenzo

doi:10.1159/000063895

Cited by 39 publications

(31 citation statements)

References 18 publications

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“…Few studies have been undertaken to measure serum cytokine levels in patients with pemphigus [14,42,43]. In these studies, while IL-6 and TNF-α levels were increased, low to undetectable levels of IL-8 and IFN-γ were found in serum of pemphigus patients.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

2012

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Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B max (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEXmediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7±2.8 vs.8.1±1.3) and Bmax (6.5±0.9 vs. 3.9±0.3) were higher in pemphigus than controls (p00.002). Considering the values above the 95th percentile of normal group as a cut-off (K d >24.9 nM and B max >8.1 fmol/mg protein), elevated K d and B max were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p00.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p<0.001) in both pemphigus and control groups. IL-6 and TNFα (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p00.002) in controls and remained elevated in pemphigus (p<0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

2012

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“…The serum factors implicated in apoptolysis include Fas ligand (FasL) (14), tumor necrosis factor ␣ (15,16), interleukins 1, 6, 8, and 15 (15,(17)(18)(19), nitric oxide (9,20), kallikreins, and other proteases (21). Using an organ culture model of PV, it has been demonstrated that PVIgG works together with FasL and tumor necrosis factor ␣ to induce apoptolysis (22).…”

Section: Pemphigus Vulgaris (Pv)mentioning

confidence: 99%

Antimitochondrial Autoantibodies in Pemphigus Vulgaris

Marchenko

Chernyavsky

Arredondo

et al. 2010

Journal of Biological Chemistry

115

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A loss of epidermal cohesion in pemphigus vulgaris (PV) results from autoantibody action on keratinocytes (KCs) activating the signaling kinases and executioner caspases that damage KCs, causing their shrinkage, detachment from neighboring cells, and rounding up (apoptolysis). In this study, we found that PV antibody binding leads to activation of epidermal growth factor receptor kinase, Src, p38 MAPK, and JNK in KCs with time pattern variations from patient to patient. Both extrinsic and intrinsic apoptotic pathways were also activated. Although Fas ligand neutralizing antibody could inhibit the former pathway, the mechanism of activation of the latter remained unknown. PV antibodies increased cytochrome c release, suggesting damage to mitochondria. The immunoblotting experiments revealed penetration of PVIgG into the subcellular mitochondrial fraction. The antimitochondrial antibodies from different PV patients recognized distinct combinations of antigens with apparent molecular sizes of 25, 30, 35, 57, 60, and 100 kDa. Antimitochondrial antibodies were pathogenic because their absorption abolished the ability of PVIgG to cause keratinocyte detachment both in vitro and in vivo. The downstream signaling of antimitochondrial antibodies involved JNK and late p38 MAPK activation, whereas the signaling of anti-desmoglein 3 (Dsg3) antibody involved JNK and biphasic p38 MAPK activation. Using KCs grown from Dsg3؊/؊ mice, we determined that Dsg3 did not serve as a surrogate antigen allowing antimitochondrial antibodies to enter KCs. The PVIgG-induced activation of epidermal growth factor receptor and Src was affected neither in Dsg3KCs nor due to absorption of antimitochondrial antibodies. These results demonstrated that apoptolysis in PV is a complex process initiated by at least three classes of autoantibodies directed against desmosomal, mitochondrial, and other keratinocyte self-antigens. These autoantibodies synergize with the proapoptotic serum and tissue factors to trigger both extrinsic and intrinsic pathways of cell death and break the epidermal cohesion, leading to blisters. Further elucidation of the primary signaling events downstream of PV autoantigens will be crucial for the development of a more successful therapy for PV patients.Pemphigus vulgaris (PV) 3 is an IgG autoantibody-mediated disease of skin and mucosa caused by a loss of epidermal cohesion and manifested by progressive blistering and non-healing erosions. The mechanism of detachment of keratinocytes (KCs) in PV, termed acantholysis, is a subject of intensive research. Elucidation of the pathophysiologic mechanism of acantholysis should facilitate development of novel pharmacologic approaches to prevent and treat blistering without systemic corticosteroids, a mainstay of treatment of PV patients. Acantholysis can be blocked both by inhibitors of signaling kinases, such as p38 MAPK (3), mammalian target of rapamycin (4), Src, and epidermal growth factor receptor (EGFR) kinase (2, 4 -7) and by other tyrosine kinases, phospholipase C, calmodulin...

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“…The result of this study showed that although the mean level of IL-10 was higher in PV patients than controls but the difference was not significant. Barioni et al 18 reported that the IL-10 levels in the serum of PV patients are below the detection limits when compared to other skin diseases. On the contrary, Bhol et al 19 and D'Auria et al, 20 reported that increased levels of IL-10 have been detected in PV patients' serum compared to normal individuals and these cytokine levels correlate with severity of disease.…”

Section: Discussionmentioning

confidence: 99%

“…In this manner, it may limit the damage and prevent more extension of lesions in the skin and mucous membranes. 18,19 However, the increased levels of these cytokines in serum of PV patients compared to normal subjects might be according to the proinflammatory or immunoregulatory action of these molecules in this autoimmune and inflammatory disease. In addition, the results of this study may have significant utility in the evaluation of chemointerventional therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

Khozeimeh¹,

Savabi²,

Esnaashari³

2014

The Journal of Contemporary Dental Practice

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Pemphigus is an autoimmune blistering disease characterized by a loss of cell adhesion result in acantholysis. Genetic factors and immunologic factors such as cytokines particularly IL-1α, IL-10, TNF-α, and TGF-β may counterpart to developing of Pemphigus. The aim of this study was to evaluate. The concentration of IL-1α, IL-10, TNF-α, TGF-β in serum of pemphigus vulgaris (PV) patients and normal individuals. Material and methods:In this analytic and descriptive study 25 patients with pemphigus vulgaris (in active phase) and 25 healthy persons were examined. Serum samples of two groups were obtained and the level of IL-1α, IL-10, TNF-α and TGF-β were measured by ELISA technique. The data were analyzed statistically by independent T test (α = 0/05).

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Cytokine Pattern in Blister Fluid and Sera of Patients with Pemphigus

Cited by 39 publications

References 18 publications

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

Antimitochondrial Autoantibodies in Pemphigus Vulgaris

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

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