PMID- 34868043
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20230519
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the 
      Presence of Systemic Disease Activity.
PG  - 775353
LID - 10.3389/fimmu.2021.775353 [doi]
LID - 775353
AB  - Cutaneous lupus erythematosus (CLE) is 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 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 inflammation relate to the 
      presence of systemic lupus disease. In 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 demonstrated 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 signatures in the lesional skin from patients with isolated CLE compared 
      with similar lesions from patients with systemic lupus. This trend 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.
CI  - Copyright (c) 2021 Abernathy-Close, Lazar, Stannard, Tsoi, Eddy, Rizvi, Yee, Myers, 
      Namas, Lowe, Reed, Wen, Gudjonsson, Kahlenberg and Berthier.
FAU - Abernathy-Close, Lisa
AU  - Abernathy-Close L
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, MI, United States.
FAU - Lazar, Stephanie
AU  - Lazar S
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, MI, United States.
FAU - Stannard, Jasmine
AU  - Stannard J
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, MI, United States.
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.
FAU - Tsoi, Lam C
AU  - Tsoi LC
AD  - Department of Dermatology, University of Michigan, Ann Arbor, MI, United States.
AD  - Department of Computational Medicine & Bioinformatics, University of Michigan, 
      Ann Arbor, MI, United States.
AD  - Department of Biostatistics, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Eddy, Sean
AU  - Eddy S
AD  - Division of Nephrology, Department of Internal Medicine, University of Michigan, 
      Ann Arbor, MI, United States.
FAU - Rizvi, Syed M
AU  - Rizvi SM
AD  - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Yee, Christine M
AU  - Yee CM
AD  - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Myers, Emily M
AU  - Myers EM
AD  - Lifebridge Health, Baltimore, MD, United States.
FAU - Namas, Rajaie
AU  - Namas R
AD  - Division of Rheumatology, Department of Internal Medicine, Cleveland Clinic Abu 
      Dhabi, Abu Dhabi, United Arab Emirates.
FAU - Lowe, Lori
AU  - Lowe L
AD  - Department of Dermatology, University of Michigan, Ann Arbor, MI, United States.
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
FAU - Reed, Tamra J
AU  - Reed TJ
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, MI, United States.
FAU - Wen, Fei
AU  - Wen F
AD  - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Gudjonsson, Johann E
AU  - Gudjonsson JE
AD  - Department of Dermatology, University of Michigan, Ann Arbor, MI, United States.
FAU - Kahlenberg, J Michelle
AU  - Kahlenberg JM
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, MI, United States.
FAU - Berthier, Celine C
AU  - Berthier CC
AD  - Division of Nephrology, Department of Internal Medicine, University of Michigan, 
      Ann Arbor, MI, United States.
LA  - eng
GR  - R03 AR072107/AR/NIAMS NIH HHS/United States
GR  - P30 AR075043/AR/NIAMS NIH HHS/United States
GR  - R01 AI130025/AI/NIAID NIH HHS/United States
GR  - R03 AR066337/AR/NIAMS NIH HHS/United States
GR  - S10 OD020053/OD/NIH HHS/United States
GR  - K24 AR076975/AR/NIAMS NIH HHS/United States
GR  - P30 DK081943/DK/NIDDK NIH HHS/United States
GR  - R01 AR071384/AR/NIAMS NIH HHS/United States
GR  - UL1 TR002240/TR/NCATS NIH HHS/United States
GR  - P30 CA046592/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20211119
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulins)
SB  - IM
MH  - B-Lymphocytes/*immunology/*metabolism
MH  - *Biomarkers
MH  - Computational Biology/methods
MH  - Diagnosis, Differential
MH  - *Disease Susceptibility
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Immunoglobulins/genetics
MH  - Immunohistochemistry
MH  - Lupus Erythematosus, Cutaneous/diagnosis/*etiology/*metabolism
MH  - Lupus Erythematosus, Systemic/diagnosis/*etiology/*metabolism
PMC - PMC8640489
OTO - NOTNLM
OT  - B cells
OT  - autoantibodies
OT  - cutaneous lupus
OT  - discoid
OT  - lupus
OT  - transcriptomic
COIS- JMK has received Grant support from Q32 Bio, Celgene/BMS, Ventus Therapeutics, 
      and Janssen. JG has received Grant support from Celgene/BMS, Janssen, Eli Lilly, 
      and Almirall. JMK has served on advisory boards for AstraZeneca, Eli Lilly, 
      GlaxoSmithKline, Bristol Myers Squibb, Avion Pharmaceuticals, Provention Bio, 
      Aurinia Pharmaceuticals, Ventus Therapeutics, and Boehringer Ingelheim. JG has 
      served on advisory boards for AstraZeneca, Sanofi, Eli Lilly, Boehringer 
      Ingelheim, Novartis, Janssen, Almirall, BMS. The remaining authors declare that 
      the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2021/12/07 06:00
MHDA- 2022/02/11 06:00
PMCR- 2021/01/01
CRDT- 2021/12/06 09:08
PHST- 2021/09/13 00:00 [received]
PHST- 2021/11/05 00:00 [accepted]
PHST- 2021/12/06 09:08 [entrez]
PHST- 2021/12/07 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.775353 [doi]
PST - epublish
SO  - Front Immunol. 2021 Nov 19;12:775353. doi: 10.3389/fimmu.2021.775353. eCollection 
      2021.