Neonatal lupus erythematosus complicated by mucocutaneous and visceral hemangiomas.

Neonatal lupus erythematosus (NLE) is a passively acquired autoimmune syndrome resulting from transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies to the fetus. Characteristic manifestations of NLE include transient dermatitis, hepatic and hematologic abnormalities and congenital heart block. Skin lesions in NLE resemble subacute cutaneous lupus erythematosus and typically consist of annular, erythematous, scaly plaques. Telangiectasias, vascular abnormalities resulting from dilation of superficial dermal vessels, may also affect the skin in a minority of patients. The etiology of telangiectasias in NLE is unknown, but disordered angiogenesis likely plays a role. Hemangiomas are a common disorder of angiogenesis frequently encountered in infancy. There have been no reported cases of neonatal lupus associated with the development of hemangiomas. We present a case of an infant diagnosed with NLE after manifesting classic dermatitis, hepatic and hematologic abnormalities who later developed mucocutaneous and visceral hemangiomas. We further postulate that disordered angiogenesis, possibly dysregulated production of vascular endothelial growth factor, may play a primary role in the development of these cutaneous vascular lesions in NLE.

Protein transduction: identification, characterization and optimization.

Protein transduction domains (PTDs), both naturally occurring and synthetic, have been increasingly employed to deliver biologically active agents to a variety of cell types in vitro and in vivo. In addition to the previously characterized arginine-rich PTDs, including Tat (transactivator of transcription), Antp (Antennapedia) and PTD-5, we have demonstrated that lysine and ornithine, as well as arginine, homopolymers are able to mediate transduction of a wide variety of agents. To screen for optimal PTDs, we have used as a therapeutic cargo a peptide derived from IKK {IkappaB [inhibitor of NF-kappaB (nuclear factor kappaB)] kinase} beta, able to bind to the IKK regulatory subunit [NEMO (NF-kappaB essential modulator)], preventing formation of an active kinase complex. This peptide, termed NBD, is able to block activation of NF-kappaB, but not basal activity. We demonstrate that PTD-mediated delivery of NBD using certain PTDs, in particular 8K (octalysine), is therapeutic following systemic delivery in murine models of inflammatory bowel disease, diabetes and muscular dystrophy. In addition, we have developed a peptide phage display library screening method for novel transduction peptides able to facilitate tissue-specific internalization of marker protein complexes. Using this approach, we have identified transduction peptides that are able to facilitate internalization of large protein complexes into tumours, airway epithelia, synovial fibroblasts, cardiac tissue and HEK-293 (human embryonic kidney) cells in culture and/or in vivo.