Thomas Bieber

FcεRI-expressing antigen-presenting cells: new players in the atopic game

Abstract What is the role of FceRI on professional antigen-presenting cells (APCs)? Here, Thomas Bieber speculates how FceRI-expressing APCs may triger primary and secondary immune responses, T-cell skewing and inflammation.

FcϵRI on human Langerhans cells: a receptor in search of new functions

Abstract The recent demonstration that the high-affinity receptor for IgE, FcϵRI, is expressed on human Langerbans cells casts a new perspective on the function of this receptor. This observation also provides a new direction for further investigation into the pathophysiological relevance of Langerbans cells and other antigen-presenting cells in the development of atopic diseases.

Comparison of different methods for enumeration of Langerhans cells in vertical cryosections of human skin

We have quantified Langerhans cells (LC) in cryosections of normal human skin and lesional skin from patients with atopic eczema and psoriasis vulgaris using six different methods. The results from the different methods varied considerably and were sometimes contradictory, for example when LC numbers in psoriatic skin were compared with those in normal skin. Thus, in addition to the staining technique used and the selection of the dendritic cell type to be counted, the enumeration method used can also influence the quantitation of LC in normal and pathological skin.

FcεRI on antigen-presenting cells

The high-affinity receptor for IgE, Fc epsilon RI, expressed on antigen-presenting cells such as monocytes and Langerhans cells exhibits profound differences to its homologue expressed on mast cells and basophils. The lack of the beta chain, the presence of an intracellular pool of preformed alpha chains, highly variable surface expression, and its function (to provide antigen focusing for T cells) are some of the main issues which have led us to consider the functional role of this receptor in a new light.

Fc epsilon RI on human epidermal langerhans cells : An old receptor with new structure and functions

Structural and functional analysis of the high-affinity receptor for IgE (Fc epsilonRI) on Langerhans cells (LCs) has highlighted new aspects of the biology of this structure when expressed on antigen-presenting cells. In contrast to effector cells of anaphylaxis, i.e. basophils and mast cells, where Fc epsilonRI is a tetrameric structure constitutively expressed at high levels, this receptor on LCs lacks the classical beta-chain and its expression varies depending on the donor and the inflammatory environment of the cells in the skin. Although the signalling pathway seems to be similar to that of basophils or mast cells, only LCs from individuals with atopic dermatitis are fully activated by receptor ligation while LCs from normal individuals fail to exhibit calcium mobilization. LCs from normal and atopic individuals use Fc epsilonRI to maximize antigen uptake via specific IgE and subsequent presentation to T cells and may be responsible for driving the T cell response in either Th0, Th1 or Th2 type.

New insights in the structure and biology of the high affinity receptor for IgE (FcϵRI) on human epidermal Langerhans cells

Abstract The recent structural and functional analysis of the high affinity receptor for IgE (FcϵRI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of FcϵRI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical β-chain. This also implies functional differences most probably related to the expression level. Although the signalling pathway seems to be similar to that of basophils or mast cells, LC from individuals with atopic dermatitis are fully activated by receptor ligation while LC from normal individuals fail to exhibit calcium mobilization under the same conditions. Finally, LC from normal and atopic individuals use FcϵRI to maximize antigen uptake via specific IgE and subsequent presentation to T cells. Thus, FcϵRI expressed on LC differs in terms of structure and function from that expressed on effector cells of anaphylaxis.

Clinical and biological effects of balneotherapy with selenium‐rich spa water in patients with psoriasis vulgaris

Omeprazole is rapidly metabolized by the cytochrome P450 system in the liver,^ and 80% of its metabolites (hydroxyand sulphone-omeprazole) are excreted in the urine, the remainder being excreted in the bile. A dosage reduction of omeprazole has not been recommended in patients with impaired renal or hepatic function, or in elderly patients. In chronic renal failure, the pharmacokinetics of omeprazole did not differ from those in healthy subjects.^ In elderly healthy volunteers aged 75-79 years, a two-fold decrease in clearance of omeprazole has been observed.^ In liver cirrhosis, the elimination half-life of omeprazole is increased, but there is no acctunulation of omeprazole and its metabolites in the body. In a recent study of eight patients with cirrhosis (median age 63 years), the mean maximal plasma concentration of omeprazole after an oral dose of 40 mg was almost three times higher than in young healthy volunteers, with a mean elimination half-life of 3 h vs. 0-7h. Although the hydroxylation of omeprazole was reduced, no omeprazole was found in the urine, the drug being metabolized chiefly by sulpho-conjugation. In our patient, high plasma concentrations of omeprazole might have been reached, due to his age, decompensating liver cirrhosis, and also concomitant treatment with allopurinol. a drug which inhibits the cytochrome P450 system.^ In conclusion, a severe but reversible toxic bullous skin reaction induced by omeprazole occurred in a patient who may bave had a high circulating level of the drug due to a combination of old age, decompensating liver cirrhosis, and drug interaction. We therefore consider it is justifiable to recommend caution in the use of omeprazole in patients who have severe cirrhosis.

CD1 expression is not affected by human peptide transporter deficiency

Conventional major histocompatibility complex class I molecules are highly polymorphic and present peptides to cytotoxic T cells. These peptides derive from the proteolytic degradation of endogenous proteins in the cytosol and are translocated into the endoplasmic reticulum by a peptide transporter consisting of two transporter associated with antigen processing (TAP) molecules. Absence of this transporter leads to the synthesis of unstable peptide free class I molecules that are weakly expressed on the cell surface. Mouse nonconventional class I molecules (class Ib) may also present TAP-dependent peptides. In humans, CD1 antigens are nonconventional class I molecules. Recently, we characterized a human HLA class I deficiency resulting from a homozygous TAP deficiency. We show here that CD1a and -c are normally expressed on epidermal Langerhans cells of the TAP-deficient patients, as are CD1a, -b, and -c on dendritic cells differentiated in vitro from monocytes. Moreover, the CD1a antigens present on the surface of the dendritic cells are functional, since they internalize by receptor-mediated endocytosis gold-labeled F(ab)2 fragments of an anti-CD1a mAb. This suggests either that CD1 molecules are empty molecules, that they are more stable than empty conventional class I proteins, or that CD1 molecules present TAP-independent peptides.

Is the atypical neutrophilic dermatosis with subcorneal IgA deposits a variant of pemphigus foliaceus.

Microscopie electronique et immunohistochimie a partir dun cas clinique pour mettre en evidence un lien entre les 2 affections

Keratinocytes in lesional skin of atopic eczema bear HLA-DR, CD1a and IgE molecules

Apparently normal, and lesional skin from patients with atopic eczema were investigated immunohistochemically with anti‐HLA‐DR, ‐CD1a and ‐IgE antisera. A CD1a + intercellular pattern was observed in uninvolved skin in the majority of the patients whereas an HLA‐DR +/CD1a+ network, mostly localized in basal and supra‐basal areas, was shown in lesional skin of virtually all of them. Moreover, an HLA‐DR +/CD1a + IgE + intercellular pattern was observed in some of the patients only and was predominantly localized in those areas characterized by lymphocyte exocytosis, spongiosis or vesicle formation. Whether keratinocytes are able to synthesize CD1a antigen and FcɛR or if these molecules are only produced and shed by CD1a +/IgE + epidermal dendritic cells remains unclear.