title: The expression of BAFF, APRIL and TWEAK is altered in eczema skin but not in the circulation of atopic and seborrheic eczema patients.
abstract: The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE.
authors.affiliation: Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Chen
authors.forename: Sara
authors.initials: S
authors.lastname: Lind Enoksson
authors.forename: Catharina
authors.initials: C
authors.lastname: Johansson
authors.forename: Maria A
authors.initials: MA
authors.lastname: Karlsson
authors.forename: Lena
authors.initials: L
authors.lastname: Lundeberg
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D000074049:Cytokine TWEAK; D003876:Dermatitis, Atopic / Q000097:blood* / Q000473:pathology; D012628:Dermatitis, Seborrheic / Q000097:blood* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D000074050:TWEAK Receptor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood* / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D000074049:Cytokine TWEAK; D020382:Interleukin-18; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C109743:TNFSF12 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D000074050:TWEAK Receptor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048069:Tumor Necrosis Factors; D007371:Interferon-gamma