Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-08-01
|
Series: | Journal of Clinical Medicine |
Subjects: | |
Online Access: | https://www.mdpi.com/2077-0383/8/8/1244 |
id |
doaj-d14257c002024adaa1e195247e5312b4 |
---|---|
record_format |
Article |
spelling |
doaj-d14257c002024adaa1e195247e5312b42020-11-25T02:17:11ZengMDPI AGJournal of Clinical Medicine2077-03832019-08-0188124410.3390/jcm8081244jcm8081244Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical PhenotypesCeline C. Berthier0Lam C. Tsoi1Tamra J. Reed2Jasmine N. Stannard3Emily M. Myers4Rajaie Namas5Xianying Xing6Stephanie Lazar7Lori Lowe8Matthias Kretzler9Johann E. Gudjonsson10J. Michelle Kahlenberg11Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Dermatology, Department of Computational Medicine & Bioinformatics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADivision of Rheumatology, Department of Internal medicine, University of Michigan, Ann Arbor, MI 48109, USAIHA Rheumatology Consultants, Ann Arbor, MI 48109, USALifebridge Health, Baltimore, MD 21215, USADivision of Rheumatology, Department of Internal Medicine, Cleveland Clinic Abu Dhabi, 112412 Abu Dhabi, United Arab EmiratesDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USADivision of Rheumatology, Department of Internal medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Dermatology, Department of Computational Medicine & Bioinformatics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADivision of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USADivision of Rheumatology, Department of Internal medicine, University of Michigan, Ann Arbor, MI 48109, USACutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making.https://www.mdpi.com/2077-0383/8/8/1244systemic lupus erythematosusinterferoncutaneous lupusdiscoid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Celine C. Berthier Lam C. Tsoi Tamra J. Reed Jasmine N. Stannard Emily M. Myers Rajaie Namas Xianying Xing Stephanie Lazar Lori Lowe Matthias Kretzler Johann E. Gudjonsson J. Michelle Kahlenberg |
spellingShingle |
Celine C. Berthier Lam C. Tsoi Tamra J. Reed Jasmine N. Stannard Emily M. Myers Rajaie Namas Xianying Xing Stephanie Lazar Lori Lowe Matthias Kretzler Johann E. Gudjonsson J. Michelle Kahlenberg Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes Journal of Clinical Medicine systemic lupus erythematosus interferon cutaneous lupus discoid |
author_facet |
Celine C. Berthier Lam C. Tsoi Tamra J. Reed Jasmine N. Stannard Emily M. Myers Rajaie Namas Xianying Xing Stephanie Lazar Lori Lowe Matthias Kretzler Johann E. Gudjonsson J. Michelle Kahlenberg |
author_sort |
Celine C. Berthier |
title |
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes |
title_short |
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes |
title_full |
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes |
title_fullStr |
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes |
title_full_unstemmed |
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes |
title_sort |
molecular profiling of cutaneous lupus lesions identifies subgroups distinct from clinical phenotypes |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-08-01 |
description |
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making. |
topic |
systemic lupus erythematosus interferon cutaneous lupus discoid |
url |
https://www.mdpi.com/2077-0383/8/8/1244 |
work_keys_str_mv |
AT celinecberthier molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT lamctsoi molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT tamrajreed molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT jasminenstannard molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT emilymmyers molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT rajaienamas molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT xianyingxing molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT stephanielazar molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT lorilowe molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT matthiaskretzler molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT johannegudjonsson molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes AT jmichellekahlenberg molecularprofilingofcutaneouslupuslesionsidentifiessubgroupsdistinctfromclinicalphenotypes |
_version_ |
1724887774731960320 |