Identification of vaccine candidate antigens of Staphylococcus pseudintermedius by whole proteome characterization and serological proteomic analyses.

The recent emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) has complicated considerably the treatment of infections caused by these bacteria. Therefore new treatment strategies are urgently needed, namely through the development of vaccines towards the control of bacterial infections. Our study describes an extensive characterization of the proteome of S. pseudintermedius through a 2-DE MALDI-TOF/TOF approach, followed by SERological Proteome Analysis (SERPA) to identify potential vaccine candidate antigens. We were able to identify 361 unique proteins, of which 39 are surface proteins. In order to assess the immunogenic potential of S. pseudintermedius proteins, a Western blot analysis of two-dimensional gels was carried out with serum from healthy dogs, dogs with atopic dermatitis infected and not infected with S. pseudintermedius. Only immunogenic areas detected by ≥ 50% of the dogs with atopic dermatitis infected with S. pseudintermedius sera and by <50% of the healthy dogs sera were excised and identified from Coomassie-colloidal stained gels. The areas identified by IgE were not considered as vaccine targets, because those proteins could induce hypersensitivity. We were able to identify 13 unique proteins after in-gel digestion of selected protein gel spots, with 4 antigenic proteins showing promising features for vaccine development. No specific antibodies were identified in the dogs with atopic dermatitis not infected with S. pseudintermedius sera that could contribute to prevention of infection. The SERPA approach employed in this study revealed novel candidate therapeutic targets for the control of S. pseudintermedius infections.

Karyotypic analysis of bone marrow cells in pyodermic lesions associated with myelodysplastic syndrome.

BACKGROUND: Recalcitrant pyodermic lesions and neutrophilic dermatoses are often associated with subclinical myelodysplastic syndrome (MDS). In this case series, we assessed the diagnostic importance of karyotypic analysis of bone marrow cells in 4 patients with MDS-associated pyodermic eruptions treated at our university hospital. Karyotypic analysis was performed in bone marrow cells and peripheral blood lymphocytes obtained. Serum levels of granulocyte colony-stimulating factor were measured. OBSERVATIONS: Four patients with pyodermic eruptions or neutrophilic dermatosis had chromosomal abnormalities in bone marrow cells, including del(20)(q11;q13.3) in 2 patients, trisomy 8 in 1 patient, and t(11;22)(q23;q11) in 1 patient. Three patients without morphologic findings suggestive of MDS were diagnosed as having refractory anemia. One female patient had refractory anemia with ringed sideroblasts associated with del(20). Two patients with refractory anemia had a normal karyotype in peripheral blood lymphocytes. Two patients with elevated serum levels of granulocyte colony-stimulating factor had more active or widespread cutaneous diseases. CONCLUSIONS: Karyotypic analysis of bone marrow cells, but not of peripheral blood lymphocytes, is essential in proving a diagnosis of MDS-associated pyodermic lesions. The overexpression of granulocyte colony-stimulating factor, which may compensate for impaired hematopoiesis in patients with MDS, seems to be a key cytokine leading to neutrophilic infiltration.

Abnormal production of tumor necrosis factor (TNF) -- alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome [corrected].

We report a family with pyogenic sterile arthritis, pyoderna and acne syndrome (PAPA). The proband presented several episodes of sterile pyogenic arthritis and became unresponsive to glucocorticoids. After treatment with the tumor necrosis factor inhibitor etanercept, the disease underwent rapid and sustained clinical remission. Production of tumor necrosis factor-alpha by mononuclear cells of the proband and of the affected relatives was abnormally elevated.

German shepherd dog pyoderma: a genetic disorder.

In this study the pedigrees of 42 German Shepherd dogs with German Shepherd dog Pyoderma (GSP) were analysed. Parents, littermates and offspring of the affected dogs were traced and their owners were questioned on characteristic skin lesions. Evidence suggesting an autosomal recessive trait was found. Breeders are advised to exclude affected animals and their relatives from further breeding.

Pyoderma gangrenosum in a kindred. Precipitation by surgery or mild physical trauma.

Five cases of pyoderma gangrenosum occurring in a kindred are presented. Three of the cases occurred after abdominal surgery and tended to be confused with postoperative wound infections. Two cases occurred after superficial injury to the leg and were also thought to represent a peculiar form of cellulitis. None of the patients are known to have any of the underlying diseases usually associated with pyoderma gangrenosum. The cases are presented to alert the physician to this entity and to document the unusual familial occurrence.

Recurrent pyoderma in a family with a defect in leucocyte locomotion.

Granulocyte functions including leucocyte locomotion and chemoluminescence were studied in three generations of a family in which all male members had presented with recurrent pyoderma. While parameters of humoral immunity including serum concentrations of IgG, IgA, IgM, and IgE and of complement components C3 and C4 as well as the response of mononuclear leucocytes to mitogens proved to be within the normal range, leucocyte locomotion was found to be severely impaired in all affected subjects. Moreover, granulocyte dysfunction in male members was associated with the occurrence of a single haplotype (HLA-A2, B13, DR7). These findings suggest that the defect in leucocyte locomotion and the pyoderma might not only have been inherited in an X linked manner but might also have been linked to a gene within the inherited HLA haplotype.

Pyoderma gangrenosum associated with selective hereditary IgA deficiency.

A case of pyoderma gangrenosum is described in a girl aged 4. The condition was associated with selective IgA deficiency. The father and the 2 brothers suffered from the same deficiency (autosomal dominant transmission). Treatment with prednisolone and clofazimine produced an excellent clinical response.

Chronic blepharitis and pyoderma of the scalp: an immune deficiency state in a father and son with hypercupremia and decreased intracellular killing.

An immune deficiency state is proposed as the cause of a disorder affecting a father and son with chronic dermatitis, purulent blepharitis with corneal ulceration, and scarring pyodermatous alopecia of the scalp. The results of immunologic investigation revealed abnormal neutrophil function with a variable decrease in intracellular killing, decreased lymphocyte transformation, increased serum IgG and IgE, and elevated serum copper levels. These findings will be compared with previously described immune deficiency disorders.

Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.

A new familial immunodeficiency disease characterised by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis is described in a father and son. It is accompanied by abnormalities of lymphocyte function (including defective proliferative responses to phytomitogens, and subnormal response in immunoglobulin production after stimulation of the lymphocytes by pokeweed mitogen) and defective leucocyte chemiluminescence responses, which were associated with defective ability for intracellular killing of microbial organisms. The abnormalities of lymphocyte and leucocyte function, as well as the clinical manifestations, responded dramatically to treatment with the histamine-1 antagonist, chlorpheniramine, suggesting that the underlying defect in this disease may relate to defective histamine metabolism or abnormal expression of histamine receptors on lymphocytes and leucocytes.

Repeated staphylococcal pyoderma in two siblings with defective neutrophil bacterial killing.

2 children with undue susceptibility to skin infections and isolated defective neutrophil bacterial killing are described. Since the NBT-reducing capabilities of granulocytes were normal, a mild form of chronic granulomatous disease was excluded. Ascorbic acid was effective in delaying and eventually suppressing infectious episodes.