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Silvia Moretti

Publications and source records attributed to Silvia Moretti.

8 recordsLinked to original sources
PubMed2004

TLRs govern neutrophil activity in aspergillosis.

Polymorphonuclear neutrophils (PMNs) are essential in initiation and execution of the acute inflammatory response and subsequent resolution of fungal infection. PMNs, however, may act as double-edged swords, as the excessive release of oxidants and proteases may be responsible for injury to organs and fungal sepsis. To identify regulatory mechanisms that may balance PMN-dependent protection and immunopathology in fungal infections, the involvement of different TLR-activation pathways was evaluated on human PMNs exposed to the fungus Aspergillus fumigatus. Recognition of Aspergillus and activation of PMNs occurred through the involvement of distinct members of the TLR family, each likely activating specialized antifungal effector functions. By affecting the balance between fungicidal oxidative and nonoxidative mechanisms, pro- and anti-inflammatory cytokine production, and apoptosis vs necrosis, the different TLRs ultimately impacted on the quality of microbicidal activity and inflammatory pathology. Signaling through TLR2 promoted the fungicidal activity of PMNs through oxidative pathways involving extracellular release of gelatinases and proinflammatory cytokines while TLR4 favored the oxidative pathways through the participation of azurophil, myeloperoxidase-positive, granules and IL-10. This translated in vivo in the occurrence of different patterns of fungal clearance and inflammatory pathology. Both pathways were variably affected by signaling through TLR3, TLR5, TLR6, TLR7, TLR8, and TLR9. The ability of selected individual TLRs to restore antifungal functions in defective PMNs suggests that the coordinated outputs of activation of multiple TLRs may contribute to PMN function in aspergillosis.

Animals↗
PubMed2004

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo.

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

Adolescent↗
PubMed2003

A case of chronic herpes gestationis: persistent disease or conversion to bullous pemphigoid?

We report the case of a 38-year-old woman with herpes gestationis (HG) persistent for 26 months postpartum with typical erythematous-edematous grouped lesions associated with vesicles, blisters, and scaled crusts on most parts of her body. Despite high doses of oral prednisolone, azathioprine, and dapsone, and a trial of 5 plasmaphereses, the disease has persisted to date. Histopathologic examination of lesional skin showed subepidermal blisters, focal basal cell necrosis, and a dermal inflammatory infiltrate including many eosinophils. Direct immunofluorescence showed linear C3 staining in the basement membrane zone and the complement fixation test demonstrated circulating antibasement membrane zone antibodies at a low titer (1:80). HLA typing demonstrated an A2, A24, B35, B52, DR4,5, DR13,15, DRW52,53 phenotype. We present this case as chronic persistent HG and discuss the differential diagnosis between chronic persistent HG and HG evolving to bullous pemphigoid, together with a careful examination of similar cases reported in literature.

Adult↗
PubMed2002

New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.

Adult↗
PubMedDate not supplied

Subacute cutaneous lupus erythematosus in childhood.

We report a 7-year-old girl who presented with erythematous-infiltrated, figurate, well-defined lesions over sun-exposed skin and antinuclear and Ro/SSA antibodies. Lupus band test revealed granular IgM and microgranular C3 deposits at the dermoepidermal junction. Histopathologic examination of lesional skin showed orthohyperkeratosis, epidermal atrophy, widespread hydropic degeneration of the epidermal basal cell layer, and a dermal perivascular lymphohistiocytic infiltrate. The clinical, immunopathologic, and histopathologic findings were consistent with the diagnosis of annular-polycyclic variant of subacute cutaneous lupus erythematosus (SCLE). Treatment with hydroxychloroquine cleared the cutaneous lesions. We report this patient because SCLE is extremely rare in childhood, and discuss the two previous cases reported in the literature.

Acute Disease↗
PubMedDate not supplied

Cutaneous sarcoid-like granulomas in a patient with X-linked hyper-IgM syndrome.

We describe a 5-year-old boy with red-pink, firm, nodular lesions, with central resolution and prominent borders, localized to the face, backs of the hands, extensor surfaces of the arms and legs, and the buttocks. He also had recurrent bacterial respiratory infections. Quantitative immunoglobulin levels revealed hypogammaglobulinemia and increased IgM levels. Histopathologic examination of a nodular lesion revealed perivascular and periadnexal granulomas composed of epithelioid cells surrounded by a mantle of lymphocytes; three cultures for fungi and acid-fast bacilli were negative. Clinical, histopathologic, and immunologic studies supported a diagnosis of hyper-IgM (HIM) syndrome. The boy was treated with pulsed-dose antibiotics and intravenous gamma globulin every 3 weeks, with improvement of clinical symptoms. Skin lesions were treated with topical corticosteroids, with immediate recurrence upon cessation of therapy. To the best of our knowledge, this is the first description of cutaneous granulomas in HIM syndrome.

Agammaglobulinemia↗