(C) The yellow module eigengene was significantly correlated with IFN score (r = 0

(C) The yellow module eigengene was significantly correlated with IFN score (r = 0.85, p = 3E-28). and DLE patients. Immune cell populations in the skin were quantified in SCLE, ACLE, and DLE lesions. DataSheet_3.pdf (587K) GUID:?E6652E2C-62DB-42A1-BE4F-18EEC1629C9B Supplementary Physique?4: Immunohistochemistry staining for B cell subsets in lesional skin from additional patients Ensartinib hydrochloride with DLE, ACLE, or SCLE. Formalin-fixed paraffin embedded tissue sections from skin were stained for CD20+ B cells and CD27+ mature B cells (n = 3 patients per CLE subtype). Representative images are shown at 100X magnification with a scale bar of 200 m. Image_4.jpeg (235K) GUID:?D1F1AB8A-6381-4EAA-BE15-660D89CAF79A Table_1.pdf (99K) GUID:?19C8E729-2A2A-4055-9B25-1EBCA1840516 Supplementary Table?2: Ingenuity pathway analysis from the 32 WGCNA cyan module genes: regulated canonical pathways. B cell-related pathways are highlighted in strong. Table_2.pdf (481K) GUID:?D23C6A37-8326-4B57-B196-524EC1CE62D2 Table_3.pdf (106K) GUID:?34844822-6756-43C4-BFF8-2BA4CFEABF60 Table_4.pdf (179K) GUID:?9CB89DF2-1ED1-4C5D-9529-ED3A2055D9D3 Data Availability StatementThe initial contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/ under the accession numbers “type”:”entrez-geo”,”attrs”:”text”:”GSE184989″,”term_id”:”184989″GSE184989 and “type”:”entrez-geo”,”attrs”:”text”:”GSE81071″,”term_id”:”81071″GSE81071 (https://www.ncbi.nlm.nih.gov/geo/). Abstract Cutaneous lupus erythematosus (CLE) is usually a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is usually a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous Ensartinib hydrochloride inflammation relate to the presence of systemic lupus disease. In Ensartinib hydrochloride this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we exhibited a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell NF1 signatures in the lesional skin from patients with isolated CLE compared with comparable lesions from patients with systemic lupus. This pattern was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity. Keywords: lupus, discoid, B cells, transcriptomic, cutaneous lupus, autoantibodies Introduction Systemic lupus erythematosus (SLE) is usually complex, chronic, autoimmune disease characterized by hyperreactive B cells and the production of pathogenic autoantibodies (1). SLE involves multiple organ systems, including the skin, where the distinct type of inflammation is usually termed cutaneous lupus erythematosus (CLE). CLE can occur in isolation or as a skin manifestation associated with underlying systemic lupus erythematosus (SLE) (2). CLE is usually relatively understudied compared to SLE, which contributes to a lack of understanding of disease heterogeneity in CLE pathogenesis. CLE is usually a rubric which encompasses clinically and histologically distinct subtypes of CLE: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), or chronic lupus erythematosus (CCLE), with discoid lupus erythematosus (DLE) being the most common subtype (3C5). While there are consistently observed Ensartinib hydrochloride cellular and molecular features in patients with CLE and/or SLE, such as a type I interferon (IFN) gene signature in the blood and skin (6C10) and peripheral B cell dysfunction (11, 12), the shared and unique molecular and cellular features Ensartinib hydrochloride of ACLE, SCLE, and CCLE remain poorly comprehended. Indeed, basic transcriptional comparisons have not identified strong distinguishing molecular signatures between subtypes (13, 14). Further, DLE is usually more likely to occur without underlying SLE compared to ACLE or SCLE (2, 15), yet it is not clear if the presence or absence.

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