Lichen planopilaris and pseudopelade of Brocq involve distinct disease associated gene expression patterns by microarray Mei Yu a,b , Robert H. Bell c , Elizabeth K. Ross a , Blanche K.K. Lo a , Megan Isaac-Renton a , Magda Martinka d , Anne Haegert c , Jerry Shapiro a , Kevin J. McElwee a,b, * a Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada b Vancouver Coastal Health Research Institute, Vancouver, Canada c Prostate Centre, Vancouver General Hospital, Vancouver, Canada d Department of Pathology, University of British Columbia, Vancouver, Canada 1. Introduction Cicatricial alopecias are a rare and varied group of disorders characterized by irreversible loss of hair. These types of alopecias often begin insidiously – loss of hair is typically gradual and may occur without symptoms – but as the disease progresses, the hair follicles are invariably replaced by scar tissue [1]. The causes of disease development are not known, but it is generally believed that inflammatory processes are involved in most scarring alopecias and immuno-modulatory treatments are used with variable results [2,3]. Histopathological examination of scalp biopsies often reveals lymphocytic and/or neutorphilic inflamma- tion that affects the upper portion of the hair follicle [4]. Based on these observations, several hypotheses have been formed to explain cicatricial alopecia disease development, commonly involving an autoimmune inflammatory cell mediated destruction of the hair follicle [5]. Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB) are two scarring alopecia diagnoses that often exhibit similar clinical Journal of Dermatological Science 57 (2010) 27–36 ARTICLE INFO Article history: Received 2 April 2009 Received in revised form 19 October 2009 Accepted 22 October 2009 Keywords: Lichen planopilaris Pseudopelade of Brocq Cicatricial alopecia Microarray ABSTRACT Background: Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB) are two scarring alopecia diagnoses that exhibit similar clinical features. Some suggest LPP and PPB are not distinct diseases, but rather different clinical presentations in a spectrum derived from the same underlying pathogenic mechanism. Objective: We explored the degree of similarity between LPP and PPB gene expression patterns and the potential for common and unique gene pathway and gene activity in LPP and PPB using microarrays. Methods: Microarray analysis, using a 21K cDNA set, was performed on pairs of biopsies obtained from affected and unaffected scalp of untreated patients. Diagnosis was confirmed by histopathology. Significantly differentially expressed genes were identified by analysis of microarray results in various datasets and screened for signaling pathway involvement. Selected genes were validated by quantitative PCR and immunohistology. Results: The global gene expression profiles in LPP and PPB versus comparative intra-control scalp tissue were distinguishable by significance analysis of microarrays (SAM). There was limited commonality in the gene expression profiles between LPP and PPB. Specific genes, such as MMP11, TNFSF13B, and APOL2, were identified with significantly differential expression in association with LPP versus PPB. Conclusions: Our findings may have important implications for understanding the pathogenesis of LPP and PPB at the molecular level. Results suggest LPP and PPB involve different mechanisms of disease development and should be regarded as biologically distinct cicatricial alopecia diagnoses. Genes that we have identified may be useful as markers of the respective diagnoses and may be potential therapeutic targets. ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. Abbreviations: APOL2, apolipoprotein L2; FDR, false discovery rate; GO, Gene Ontology; LPP, lichen planopilaris; MMP11, matrix metallopeptidase 11; PPB, pseudopelade of Brocq; qPCR, quantitative reverse transcriptase PCR; TNFSF13B, tumor necrosis factor (ligand) superfamily, member 13b. * Corresponding author at: Department of Dermatology and Skin Science, University of British Columbia, 835 W. 10th Ave., Vancouver, BC V5Z 1L8, Canada. Tel.: +1 604 875 4747; fax: +1 604 875 9919. E-mail address: kevin@keratin.com (K.J. McElwee). Contents lists available at ScienceDirect Journal of Dermatological Science journal homepage: www.elsevier.com/jds 0923-1811/$36.00 ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jdermsci.2009.10.011