Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases.

Autoimmune diseases are characterized by chronic inflammatory reactions localized to an organ or organ-system. They are caused by loss of immunologic tolerance toward self-antigens, causing formation of autoantibodies that mistakenly attack their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in which the underlying molecular mechanisms remain elusive. In this review, we present evidence accumulated through more than three decades that the serpin-derived protein Pso p27 is an autoantigen in psoriasis and probably also in other chronic inflammatory diseases. Pso p27 is derived from the serpin molecules SERPINB3 and SERPINB4 through non-canonical cleavage by mast cell chymase. In psoriasis, it is exclusively found in skin lesions and not in uninvolved skin. The serpins are cleaved into three fragments that remain associated as a Pso p27 complex with novel immunogenic properties and increased tendency to form large aggregates compared to native SERPINB3/B4. The amount of Pso p27 is directly correlated to disease activity, and through formation of complement activating immune-complexes, Pso p27 contribute to the inflammation in the skin lesions. SERPINB3/B4 are expressed in skin fibroblasts and keratinocytes, but normally absent in mast cells. Overexpression of the serpins may be induced by inflammation and hypoxia, resulting in mast cell uptake via yet unknown mechanisms. Here the generation and subsequent release of Pso p27 aggregates may promote an inflammatory loop that contributes to the chronicity of psoriasis and other autoimmune diseases.

A single Legionella pneumophila genotype in the freshwater system in a ship experiencing three separate outbreaks of legionellosis in 6 years.

BACKGROUND: Recurrent legionella outbreaks at one and the same location are common. We have identified a single Legionella pneumophila genotype associated with recurrent Legionella outbreaks over 6 years. METHODS: Field emergency surveys following Legionella outbreaks were performed on a vessel in 2008, 2009 and 2013. Water samples from both the distribution and technical parts of the potable water system were analyzed with respect to L. pneumophila [Real-Time PCR, cultivation, serotyping and genotyping (PFGE)] and free-living amoebae, (FLA). RESULTS: Legionella pneumophila serogroup 1 was present in the ship's potable water system during every outbreak. Genotyping of the 2008 survey material showed two separate PFGE genotypes while those in 2009 and 2013 demonstrated the presence of only one of the two genotypes. FLA with intracellular L. pneumophila of the same genotype were also detected. Analyses of the freshwater system on a ship following three separate Legionella outbreaks, for L. pneumophila and FLAs, revealed a single L. pneumophila genotype and FLA (Hartmanella). CONCLUSIONS: It is reasonable to assume that the L. pneumophila genotype detected in the freshwater system was the causal agent in the outbreaks onboard. Persistence of an apparently low-pathogenic L. pneumophila genotype and FLA in a potable water system represent a potential risk for recurrent outbreaks.

Psoriasis pathogenesis - Pso p27 constitutes a compact structure forming large aggregates.

Psoriasis is a chronic inflammatory skin disease. The absence of microbial organisms as potential causal agents has given rise to the hypothesis that the inflammation is due to an autoimmune reaction. The defined inflamed areas of the skin lesions argue for an immunological disease with a local production of a causal antigen. Pso p27 is a protein generated in mast cells in psoriatic plaques, but not in uninvolved skin. We recently demonstrated that the Pso p27 is generated by cleavage of SerpinB3 (SCCA1) in the presence of mast cell associated chymase. In this communication we demonstrate by X-ray crystallographic analysis that the cleavage products associate into a complex similar to SCCA1, but with the reactive centre loop inserted into a 5-stranded central ß-sheet. Native gel electrophoresis show that these Pso p27 complexes form large aggregates which may be of significance with respect to an immunogenic role of Pso p27.

Psoriasis pathogenesis - Pso p27 is generated from SCCA1 with chymase.

Psoriasis is a chronic inflammatory skin disease with unknown aetiology. Infiltration of inflammatory cells as the initial event in the development of new psoriatic plaques together with the defined inflamed areas of such lesions argues for an immunological disease with a local production of a causal antigen. The auto-antigen Pso p27 is a protein expressed in the skin lesions. We recently demonstrated that Pso p27 is homologous to the core amino acid sequences of squamous cell carcinoma antigens 1 and 2 (SCCA1/2) and it is apparently generated from SCCA molecules by digestion with highly specific endoproteases. In this communication we demonstrate the generation of Pso p27 from SCCA1 with extracts from psoriatic scale and even more remarkably, the generation of Pso p27 from SCCA1 in the presence of mast cell associated chymase. These findings open up for new therapeutic strategies in psoriasis and probably also in other autoimmune diseases as Pso p27 epitopes have been detected in diseased tissues from patients with various chronic inflammatory diseases.

Legionella pneumophila in Norwegian naval vessels.

BACKGROUND: Little is known about the occurrence of Legionella pneumophila in water supply systems on board ships. Our aim was to study the occurrence of L. pneumophila in the water supply system on board Norwegian naval vessels as the basis for framing preventive strategies against Legionella infection. MATERIAL AND METHOD: Water samples were collected from technical installations and from the water distribution network on board 41 vessels and from ten water filling (bunkering) stations, the sampling taking place in two rounds separated by a one-year interval. The samples were subjected to analysis, including serotyping and genotyping, with a view to identifying the presence of L. pneumophila and of free-living amoebae. RESULTS: L. pneumophila was found in 20 out of a total of 41 vessels in the first round of sampling, and live L. pneumophila serogroup 1 was isolated in seven of the 20 vessels. Free-living amoebae were found in the water supply system in most of the vessels, including all the vessels with L. pneumophila. The same genotype of L. pneumophila was identified in the water in bunkering stations and in the water on board the vessels. INTERPRETATION: L. pneumophila was not present in all the vessels, but all the vessels where the bacterium was found were also contaminated with free-living amoebae. We have demonstrated the probability of the fresh water from bunkering stations being the source of the contamination. In framing preventive strategies, importance should therefore be attached to identifying the source of contamination and the presence of free-living amoebae, as a premise for the establishment and growth of L. pneumophila in onboard water supply systems.

Concentration of circulating autoantibodies against HSP 60 is lowered through diving when compared to non-diving rats.

OBJECTIVE: Skin and ear infections, primarily caused by Pseudomonas aeruginosa (P. aeruginosa), are recurrent problems for saturation divers, whereas infections caused by P. aeruginosa are seldom observed in healthy people outside saturation chambers. Cystic fibrosis (CF) patients suffer from pulmonary infections by P. aeruginosa, and it has been demonstrated that CF patients have high levels of autoantibodies against Heat shock protein 60 (HSP60) compared to controls, probably due to cross-reacting antibodies induced by P. aeruginosa. The present study investigated whether rats immunised with P. aeruginosa produced autoantibodies against their own HSP60 and whether diving influenced the level of circulating anti-HSP60 antibodies. METHODS: A total of 24 rats were randomly assigned to one of three groups ('immunised', 'dived' and 'immunised and dived'). The rats in group 1 and 3 were immunised with the bacteria P. aeruginosa, every other week. Groups 2 and 3 were exposed to simulated air dives to 400 kPa (4 ata) with 45 min bottom time, every week for 7 weeks. Immediately after surfacing, the rats were anaesthetised and blood was collected from the saphenous vein. The amount of anti-HSP60 rat antibodies in the serum was analysed by enzyme linked immunosorbent assay. RESULTS: The immunised rats (group 1) showed a significant increase in the level of autoantibodies against HSP60, whereas no autoantibodies were detected in the dived rats (group 2). The rats both immunised and dived (group 3) show no significant increase in circulating autoantibodies against HSP60. A possible explanation may be that HSP60 is expressed during diving and that cross-reacting antibodies are bound.

The autoantigen Pso p27: a post-translational modification of SCCA molecules.

Pso p27 is a protein antigen expressed in psoriatic lesions and is shown to participate in complement activating immune complexes in the affected skin. The objective of the present study was sequencing of the Pso p27 protein in an approach to identify a "Pso p27 gene". The analyses showed that Pso p27 represents several proteins with homologies to various Squamous Cell Carcinoma Antigens (SCCAs). The unique N-terminal and C-terminal ends of Pso p27, however, differ from the terminal ends of the SCCA molecules and indicate posttranslational digestions of SCCA molecules with highly specific endoproteases. These structural variations may play crucial roles with respect to the immunogenicity of Pso p27 and the failure of immunological tolerance.

Expression of the psoriasis-associated antigen, Pso p27, is inhibited by traditional Chinese medicine.

AIM OF THE STUDY: Pso p27 is shown to be an autoantigen in psoriasis and the objective of the present study was to investigate whether Traditional Chinese Medicine (TCM) would influence the expression of Pso p27. MATERIALS AND METHODS: Skin biopsies obtained from psoriatic patients before and after treatment with TCM were analyzed for the presence of Pso p27 antigen by indirect immunofluorescence using murine monoclonal antibodies against Pso p27. RESULTS: A significant reduction in the amount of Pso p27 in the psoriatic skin was obtained after treatment with TCM for 3 months. CONCLUSIONS: The presence of Pso p27 in psoriatic skin is reduced when psoriatic patients are treated with TCM.

[Effect of combined herbal medicine therapy on the expression of psoriasis-associated antigen-Pso p27 in patients with psoriasis vulgaris].

OBJECTIVE: To evaluate the effect of combined herbal medicine therapy on the expression of psoriasis-associated antigen (Pso p27) in patients with psoriasis vulgaris. METHODS: Fifteen psoriasis vulgaris patients were included in the study and they were all treated with combined herbal medicine therapy for 12 weeks. Both psoriasis area and severity index (PASI) score and plaque index (PI) score were evaluated before and after treatment, while skin biopsies from selected lesions and uninvolved skin near the lesions were performed. Expression of Pso p27 in the target skin and surrounding uninjured skins were analysed using immunofluorescence method. RESULTS: The PASI score and PI score decreased after the combined herbal medicine therapy in both acute and silent stages (P < 0.01), so did the positive cells of Pso p27 and the intensity of fluorescein stain (P < 0.05). CONCLUSION: The combined herbal medicine therapy is effective in treating psoriasis vulgaris in both acute and silent stages, which may be resulted from its inhibition of the expression of Pso p27.