Psoriasis/Strep

[kim]

This sounds an awful lot like PANDAS to me, except the reaction is btwn skin cells and strep. The first study that discusses "peptidoglycan" i believe would implicate N acetylglucosamine in psoriasis related strep reactions, as has been found in PANDAS. Just pulled a couple of excerpts from wiki on peptidoglycan. The first study is dated 2008, so one of the more recent.

 

 

from wiki

 

http://en.wikipedia.org/wiki/Peptidoglycan

 

Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine and N-acetylmuramic acid residues. Attached to the N-acetylmuramic acid is a peptide chain of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer.

 

and

 

N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of C11H19NO8. It is part of a biopolymer in the bacterial cell wall, built from alternating units of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), cross-linked with oligopeptides at the lactic acid residue of MurNAc. This layered structure is called peptidoglycan.

 

 

 

2008

 

http://www.ncbi.nlm.nih.gov/pubmed/1704584...ogdbfrom=pubmed

 

Peptidoglycan: a major aetiological factor for psoriasis?Baker BS, Powles A, Fry L.

Department of Dermatology, Faculty of Medicine, Imperial College, St Mary's Campus, London W2 1PG, UK. drbsbaker@aol.com

 

Peptidoglycan (PG), a major cell-wall component of Gram-positive bacteria, has been detected within antigen-presenting cells in various inflammatory conditions, including psoriasis. The additional presence of T-helper 1 cells specific for streptococcal or staphylococcal PG in psoriasis skin lesions implicates PG as an important T-cell stimulator for the disease. PG is a major target for the innate immune system, and associations between genetic polymorphisms of recognition receptors for PG and various auto-inflammatory diseases have been identified. The location of these genes within four linkage sites for psoriasis raises the possibility that an altered innate recognition of PG might contribute to the enhanced T-cell response to the bacterial antigen. These observations suggest that PG is a major aetiological factor for psoriasis and emphasize the importance of PG in bacterial-infection-induced inflammatory disease.

 

2006

 

excerpt

http://www.ncbi.nlm.nih.gov/pubmed/16493599

 

Peptidoglycan and peptidoglycan-specific Th1 cells in psoriatic skin lesions.Baker BS, Laman JD, Powles A, van der Fits L, Voerman JS, Melief MJ, Fry L.

Department of Dermatology, Faculty of Medicine, St Mary's campus, Imperial College, London, UK.

 

We have previously demonstrated, in psoriatic skin lesions, the presence of a subset of dermal CD4+ T cells that produce interferon-gamma (IFN-gamma) in response to a mixture of cell wall proteins extracted from group A streptococci. However, the identity of the antigen(s) involved is unknown. To investigate the hypothesis that peptidoglycan (PG), the major constituent of the streptococcal cell wall, acts as a T cell activator in psoriasis, we performed in situ analysis to detect antigen-presenting cells containing PG in lesional versus non-lesional skin, and determined proliferation and IFN-gamma responses of lesional skin T cells. Increased numbers of PG-containing cells were detected in the dermal papillae and cellular infiltrates of guttate and chronic plaque skin lesions compared with normal and non-lesional psoriatic skin2002

 

http://www.ncbi.nlm.nih.gov/pubmed/12443847

 

CD4+ T-cells from peripheral blood of a patient with psoriasis recognize keratin 14 peptide but not 'homologous' streptococcal M-protein epitope.Kobayashi H, Takahashi M, Takahashi H, Ishida-Yamamoto A, Hashimoto Y, Sato K, Tateno M, Iizuka H.

Department of Pathology, Asahikawa Medical College, 2-1-1 Midorigaoka-Higashi, Asahikawa, Japan.

 

Psoriasis has been recognized as an immunologically mediated inflammatory skin disease that has been associated with group A, beta-haemolytic streptococcal infections. Notably cross-reactive autoimmune mechanism, which is mediated by T cells reacting to epitopes that are common to streptococcal M-protein and keratin, has been proposed in psoriasis. In order to investigate this possibility, peptides corresponding to M-protein and human epidermal keratin, which share some amino acid sequence between them, were synthesized and tested for their ability to stimulate T-cells of patients with psoriasis. Among five cases examined, we isolated a CD4(+) T-cell line that recognized the type I keratin (K14)(p168-181) when it was presented by the patient's HLA-DR molecules from a single psoriatic patient, whose MHC allele was HLA-A2/A26, -B27/B16, -DR4/DR8, -DQ8. Further analysis disclosed that the critical peptide recognized by the T-cell line was 10-mer keratin(p171-180) (DLRNKILTAT). However, corresponding M6 protein with homology to K14 did not stimulate the T-cell response and no evidence for cross-reactivity was obtained. The K14-responsive T cell line produced IFN-gamma, but little IL-4 when stimulated with irradiated autologous PBMC pulsed with this peptide. Thus, the finding that human epidermal keratin peptide is immunogenic in a psoriasis patient may provide the evidence that T lymphocytes play an important role in the pathogenesis of psoriasis as an autoimmune disorder participated with Th1 like cells. However, the keratin-responsive T cell line was detected in only one of five cases of psoriasis examined, suggesting that such T cell line appears to be not so popular in psoriatic patients. No evidence for cross-reactivity to streptococcal M protein also suggests that the contribution of streptococci may simply be inducing proliferation of various repertoire of T cells (including K14-responsive T cells) possibly through a superantigen-dependent process.

 

 

http://www.ncbi.nlm.nih.gov/sites/entrez?D...Search=17344934

 

Invest Dermatol. 2007 Jun;127(6):1337-42. Epub 2007 Mar 8. Links

Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis.El-Rachkidy RG, Hales JM, Freestone PP, Young HS, Griffiths CE, Camp RD.

Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.

 

A pathogenic role for Streptococcus (S) pyogenes infections in chronic plaque psoriasis is suspected but poorly defined. We separated cellular and supernatant proteins from S. pyogenes cultures by high-resolution two-dimensional gel electrophoresis, and used immunoblotting to demonstrate the diversity of serum or plasma IgGs that react with elements of the proteome of this bacterium. We have shown that a substantial proportion of IgG-reactive proteins from cultured S. pyogenes are secreted. The total secreted protein fraction, including diverse IgG-binding elements, was subsequently used in an ELISA to measure blood titers of reactive IgG. This ELISA showed that blood samples from patients with chronic plaque psoriasis contained significantly higher titers of reactive IgG than samples from age- and sex-matched healthy controls (P=0.0009). In contrast, neither a standard assay measuring antistreptolysin O titers nor ELISAs measuring titers of IgG reactive with protein fractions from Staphylococcus aureus and Staphylococcus epidermidis, were able to distinguish between blood samples from the two groups. These findings justify the hypothesis that S. pyogenes infections are more important in the pathogenesis of chronic plaque psoriasis than has previously been recognized, and indicate the need for further controlled therapeutic trials of antibacterial measures in this common skin disease.

 

http://www.ncbi.nlm.nih.gov/pubmed/10725825

 

A 23-year-old man had small desquamative erythematous lesions, round or oval in shape, spread over his entire body, and diagnosed as psoriasis guttate acuta because of clinical and pathological findings. Three weeks before the lesions had started, he was diagnosed as having varicella by his family physician. The psoriatic lesions appeared at the same sites where previously lesions of varicella had appeared. Therefore, VZV infection was regarded as a trigger in this case. We speculate that genetic factors and the change of skin condition are basically involved in the pathogenesis of psoriasis guttate. In addition, one more factor as a trigger is needed to cause the lesions of psoriasis. VZV infection might change the skin condition and induce subsequent immunological disregulation.

[kim]

I'm using turmeric as an antiinflam and because there is some research showing that it might be beneficial in controlling psoriasis (down regulating phosphorylase kinase). I have been trying to figure out if this might be helpful in PANDAS cases. I ran across this study (2nd one) and thought the fact that genistein, a component of soy, was capable of inhibiting invasion of strep was interesting. I'm really really not a fan of soy. fed my boys soy infant formula and wish i wouldn't have, but ths was interesting non the less. EA mom, if your reading, I'm wondering if Buster could take a look at this. I know he's very familiar with the Pandas studies and would luv his input here.

 

 

http://www3.interscience.wiley.com/journal...262209/abstract

 

ABSTRACT

Summary To determine whether abnormal activity of a calmodulin-containing enzyme which catalyses phosphorylation reactions may play a pathogenetic role in psoriasis, the presence and activity of phosphorylase kinase (PK) in human epidermis were determined in patients with untreated/active psoriasis (n=10), treated/resolving psoriasis (n= 10), and non-psoriatic controls (n= 10). Biopsies were taken from involved and uninvolved skin for PK, organic phosphorus, and inorganic phosphate estimation, and light and electron microscopy. The enzyme was present in involved and uninvolved skin of every patient in the study. PK activity (units/mg protein) was significantly higher in active psoriasis than in resolving psoriasis and controls. PK activity correlated directly with organic phosphorus levels, and inversely with the extent of cellular glycogenolysis measured by the depletion of glycogen granules within the keratinocytes. The study demonstrates that PK is present in both psoriatic and normal epidermis, with significantly higher levels in active psoriasis. Furthermore, higher levels of PK activity, glycogenolysis and phosphorylation are associated with increased clinical psoriatic activity. We conclude that PK, a calmodulin-containing enzyme, is involved in regulating calcium-dependent phosphorylation events in human epidermis, and disturbance of its activity may play a key role in the clinical manifestations of psoriasis.

 

 

bolding mine

 

http://jem.rupress.org/cgi/content/abstract/186/10/1633

 

Regulation of the Phosphorylation of Human Pharyngeal Cell Proteins by Group A Streptococcal Surface Dehydrogenase: Signal Transduction between Streptococci and Pharyngeal Cells

By Vijaykumar Pancholi and Vincent A. Fischetti

 

From the Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York 10021

 

Whether cell-to-cell communication results when group A streptococci interact with their target cells is unknown. Here, we report that upon contact with cultured human pharyngeal cells, both whole streptococci and purified streptococcal surface dehydrogenase (SDH) activate pharyngeal cell protein tyrosine kinase as well as protein kinase C, thus regulating the phosphorylation of cellular proteins. SDH, a major surface protein of group A streptococci, has both glyceraldehyde-3-phosphate dehydrogenase and ADP-ribosylating enzyme activities that may relate to early stages of streptococcal infection. Intact streptococci and purified SDH induce a similar protein phosphorylation pattern with the de novo tyrosine phosphorylation of a 17-kD protein found in the membrane/particulate fraction of the pharyngeal cells. However, this phosphorylation required the presence of cytosolic components. NH2-terminal amino acid sequence analysis identified the 17-kD protein as nuclear core histone H3. Both phosphotyrosine and phosphoserine-specific monoclonal antibodies reacted with the 17-kD protein by Western blot, suggesting that the binding of SDH to these pharyngeal cells elicits a novel signaling pathway that ultimately leads to activation of histone H3-specific kinases. Genistein-inhibitable phosphorylation of histone H3 indicates that tyrosine kinase plays a key role in this event. Treatment of pharyngeal cells with protein kinase inhibitors such as genistein and staurosporine significantly inhibited streptococcal invasion of pharyngeal cells. Therefore, these data indicated that streptococci/SDH-mediated phosphorylation plays a critical role in bacterial entry into the host cell. To identify the membrane receptor that elicits these signaling events, we found that SDH bound specifically to 30- and 32-kD membrane proteins in a direct ligand-binding assay. These findings clearly suggest that SDH plays an important role in cellular communication between streptococci and pharyngeal cells that may be important in host cell gene transcription, and hence in the pathogenesis of streptococcal infection.