A Novel Homozygous Mutation Affecting Integrin α6 in a Case of Junctional Epidermolysis Bullosa with Pyloric Atresia Detected In Utero by Ultrasound Examination

Abstract

In their abstract, Davenport et al (1997) state that ''Results consistently demonstrated that all the test sunscreens protected (against immunosuppression) beyond their designated protections factors.'' Protection factors are ratios by definition, and if the above statement by Davenport et al (1997) means anything at all, it is that the sunscreens' immune protection factors were greater than their corresponding sun protection factors (SPF). Chu et al (1998) restate their claim in their recent letter to the Journal of Investigative Dermatology in which they also state that they did not calculate immune protection factors in their original paper but would have to concede, from their own data, that had they done so, as suggested in letters by Gasparro (1998) and Wolf and Kripke (1998), these would have been lower than the corresponding SPF. If the immune protection factor is lower than the SPF, it is just not possible for sunscreens ''to protect beyond their designated protection factors.'' The authors tested products with SPF ranging from 3.6 to 5.7, and defend their original conclusions by arguing that although ex vivo skin exposed to 5 minimal erythema doses (MED) results in 50% immunosuppression, a sunscreen of SPF ϭ 5 completely protects against immunosuppression when skin is exposed to 5 MED. This is hardly surprising as 5 MED with an SPF of 5 is equivalent to 1 MED without a sunscreen, and 1 MED without sunscreen almost certainly does not cause immunosuppression in their model. All the authors can conclude from this analysis is that 1 MED delivered to the skin, with or without sunscreen, is not immunosuppressive. Furthermore, the UV dose-threshold for immunosuppression in Manuscript

Keratinocyte-Secreted Laminin 5 Can Function as a Transient Receptor for Human Papillomaviruses by Binding Virions and Transferring Them to Adjacent Cells

“…Because LN5 is the major ligand of the ␣6␤4 integrin receptor at the hemidesmosomes, we hypothesized that ␣6 integrin, a proposed HPV receptor (15), might be important for the infection of attached cells by virions preadsorbed to LN5. To test this hypothesis, we first utilized BOUA-SV cells, a keratinocyte-derived cell line which is homozygous null for ␣6 integrin (16). In independent experiments, all cell lines expressing ␣6 integrin were highly infectible by HPV-11 adsorbed to the LN5-rich ECM of HaCaT cells, whereas the BOUA-SV cells were only weakly infected by virions adsorbed to this LN5-rich substrate (Fig.…”

Different Heparan Sulfate Proteoglycans Serve asCellular Receptors for HumanPapillomaviruses

“…To further address this issue, we performed attachment assays using VLP of high-risk HPV16 and human epidermal keratinocytes as appropriate target cells. We took advantage of keratinocytes (BOUA-SV) isolated from a patient with a blistering skin disease that lacked ␣6 integrin expression due to a homozygous deletion (16). For comparison, human keratinocytes (KH-SV) isolated from healthy donor skin were used.…”

“…Keratinocytes deficient for ␣6 integrin expression (BOUA-SV) were derived from a patient with junctional epidermolysis bullosa carrying a homozygous mutation in the integrin ␣6 gene (16), and KH-SV keratinocytes were derived from a healthy donor. Both cell lines were immortalized by simian virus 40.…”

Epidermolysis Bullosa with Congenital Pyloric Atresia: Novel Mutations in the β4 Integrin Gene (ITGB4) and Genotype/Phenotype Correlations

“…Two of the ␣6 integrin cases were lethal in the early postnatal period, and in one case an affected fetus with abnormalities in the skin and intestine was detected prenatally by ultrasound examination, and the pregnancy was terminated. Subsequent immunochemical analysis of the latter case revealed altered expression of ␣6␤4 integrin (22). Therefore, neither the ␣6 nor the ␤4 integrin databases provide definitive explanations for the clinical variability, i.e.…”

“…Specifically, markedly reduced or absent staining for ␣6 and/or ␤4 integrin has been demonstrated in the skin of these patients, suggesting that the corresponding genes, ITGA6 and ITGB4, may harbor the mutations underlying this subset of EB (14 -16). Subsequently, a number of mutations in these two genes have been demonstrated, the majority of the mutations being found in the ␤4 integrin gene (10 -13, 17-20), whereas only three cases with mutations in the ␣6 integrin gene have been reported thus far (9,21,22). Two of the ␣6 integrin cases were lethal in the early postnatal period, and in one case an affected fetus with abnormalities in the skin and intestine was detected prenatally by ultrasound examination, and the pregnancy was terminated.…”