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Biomedical subjects

Barbara S Baker

Publications and source records attributed to Barbara S Baker.

6 recordsLinked to original sources
PubMed2006

Peptidoglycan: a major aetiological factor for psoriasis?

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.

Cell Wall↗
PubMed2006

The role of microorganisms in atopic dermatitis.

Atopic dermatitis (AD) is a common, fluctuating skin disease that is often associated with atopic conditions such as asthma and IgE-mediated food allergy and whose skin lesions are characterized by a Th-2 cell-mediated response to environmental antigens. The increasing prevalence and severity of atopic diseases including AD over the last three decades has been attributed to decreased exposure to microorganisms during early life, which may result in an altered Th-1/Th-2-balance and/or reduced T cell regulation of the immune response. Patients with AD exhibit defects in innate and acquired immune responses resulting in a heightened susceptibility to bacterial, fungal and viral infections, most notably colonization by S. aureus. Toxins produced by S. aureus exacerbate disease activity by both the induction of toxin-specific IgE and the activation of various cell types including Th-2 cells, eosinophils and keratinocytes. Allergens expressed by the yeast Malazessia furfur, a component of normal skin flora, have also been implicated in disease pathogenesis in a subset of AD patients. Microorganisms play an influential role in AD pathogenesis, interacting with disease susceptibility genes to cause initiation and/or exacerbation of disease activity.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Variation at the IRF2 gene and susceptibility to psoriasis in chromosome 4q-linked families.

Evidence, largely from Irish pedigrees, indicates that a susceptibility locus for psoriasis maps to chromosome 4q. The gene encoding interferon regulatory factor-2 (IRF-2) maps to this region, and, as mice lacking IRF-2 exhibit a dermatologic phenotype resembling many aspects of human psoriasis, IRF-2 represents an attractive positional candidate. We set out to establish whether variation in IRF-2 sequence or expression was related to the development of psoriasis. First, the promoter, coding, and adjacent untranslated regions of IRF-2 were screened in individuals from 4q-linked families. Neither variant identified (IVS1A+29A/G; IVS3+729T/C), however, had functional credentials or statistical evidence supporting a susceptibility role. Second, in 62 Irish parent-offspring trios ascertained for psoriasis, we conducted a linkage-disequilibrium screen of the IRF2 region using a dense microsatellite map (covering 1.5 Mb from D4S1554 to D4S1540). Though there was nominal association for D4S1554/D4S2348 haplotypes (p=0.03) with one haplotype showing particularly skewed transmission to psoriatic offspring (p=0.0002, uncorrected), these markers lie some distance (500 kb) from IRF-2. Finally, we found no abnormalities of IRF-2 protein expression or distribution in skin biopsies from psoriatic individuals. These diverse lines of inquiry allow us to exclude variation in IRF2 as responsible for the 4q-linkage signal previously identified in Irish pedigrees.

Chromosome Mapping↗
PubMed2003

Reduced IFN-gamma responses associated with HLA-DR15 presentation of streptococcal cell wall proteins to dermal Th-1 cells in psoriasis.

We have recently described a group A streptococcal (GAS)-reactive Th-1 subset specifically present in skin lesions of chronic plaque psoriasis. To investigate MHC presentation of GAS cell wall proteins, dermal T cell lines (TCL) cultured from the lesional skin of 39 HLA-typed psoriasis patients were stimulated with a cell wall extract, stained for intracellular IFN-gamma expression, and analyzed by flow cytometry. TCL from a further seven psoriasis patients were also tested with S. mutans extract. Eight TCL were tested in the presence of anti-Class II antibodies or allogeneic antigen-presenting cells. The dermal T cell IFN-gamma responses to the cell wall extract, which ranged from < 1 to 28%, were significantly higher than that to S. mutans extract (p = 0.0052) and were self-HLA-DR allele restricted. A significantly decreased response was observed in TCL from DR15+ (n = 13) versus DR15- (n = 26) patients (p = 0.0377). In addition, DR15+ patients had a later age of onset of disease and a decreased history of sore throats. In contrast, TCL from HLA-DR7+ (n = 23) patients responded similarly to those from individuals lacking the DR7 allele. However, DR7+ patients who coexpressed the MHC Class I antigen, Cw6 (n = 14) had a significantly higher IFN-gamma response than Cw6-, DR7+ patients (n = 7; p = 0.0288) whose responses were also significantly lower than those of patients expressing non-DR7 alleles (n = 16; p = 0.0302). This study has shown that HLA-DR15 expression is associated with a reduced dermal Th-1 response to GAS cell wall proteins in patients with psoriasis. It is proposed that HLA-DR allelic variation may contribute to disease phenotype via effects on the immune response to group A streptococci.

Adult↗