Elevated serum levels of C-X-C motif chemokine ligand 10 can distinguish systemic lupus erythematosus patients from cutaneous lupus erythematosus patients

Zhu, Jingfei; O’Brien, Jack C.; Barber, Grant; Saxena, Ramesh; Chong, Benjamin F.

doi:10.1016/j.jaad.2021.04.032

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…In addition, we also observed increases in a large number of C‐C motif chemokines, including Ccl19 [13.4‐fold], Ccl21a [5.2‐fold], Ccl8 [3.7‐fold], Ccl6 [2.6‐fold] in NativeMP3. Consistent with this increase in chemokines, increased plasma concentrations of many inflammatory chemokines have previously been reported in patients with systemic lupus erythematosus [26, 27]. It has been proposed that chemokine receptors (e.g., Cxcr3) play a crucial role in directing pathogenic effector T cells to the kidney in MRL‐lpr mice [28].…”

Section: Resultssupporting

confidence: 58%

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Triple‐threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL‐lpr mice

et al. 2022

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Systemic lupus erythematosus is a common autoimmune inflammatory disease which is associated with increases in autoantibodies and immune complexes that deposit in the kidney. The MRL-lpr mouse is a common mouse model used for the study of lupus and immune complex glomerulonephritis but very little is known about the plasma proteome changes in this model. We performed in-depth quantitative proteome profiling on MRL-lpr and control (strain MpJ) mice to investigate the changes in the proteome, immunoglobulins and their glycoproteome as well as protein and immune complexes. Methodologies used included immunohistochemistry, immunoglobulin isotyping, multiplexed proteome profiling, immunoglobulin immunoprecipitation with glycoproteome profiling, and size exclusion chromatography (SEC) profiling to enable a comprehensive proteome profiling of proteins and protein complexes. We also used a novel native multiplexed plasma proteome profiling (NativeMP3) method that relies on native enrichment of plasma proteins enabling ultra-deep single shot profiling where we identified 922 plasma proteins at 1% false discovery rate (FDR) in a single shot mass spectrometry run. We observed many large plasma protein differences between the MRL-lpr and control strain including differences in the immunoglobulins, immunoglobulins against specific antigens, chemokines, and proteases as well as changes in protein complexes such as the immunoproteasome.

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Section: Resultssupporting

confidence: 58%

“…In [26,27]. It has been proposed that chemokine receptors (e.g., Cxcr3) play a crucial role in directing pathogenic effector T cells to the kidney in MRL-lpr mice [28].…”

Section: Analysis Of Mrl-lpr Plasma Using Automp3 and Nativemp3mentioning

confidence: 99%

Triple‐threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL‐lpr mice

et al. 2022

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“…The interaction between CXCR3-expressing T-cells and its ligands CXCL9, CXCL10 and CXCL11 have been associated with tissue damage in several CLE subtypes( 8 ). A recent study described CXCL10 as a biomarker that can distinguish CLE patients from systemic lupus patients( 34 ). Based on our data, we would hypothesize that CXCL11 may be a superior biomarker to CXCL10 in predicting disease activity in CLE patients due to both its expression level and chemotactic potency, though this would need to be validated in a larger patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Shakiba,

Haddadi,

Afshari

et al. 2024

Preprint

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Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, includingAIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.One Sentence SummaryWe mapped chemokine orchestrators of interface dermatitis in lupus using spatial approaches on archival tissue and confirmed with fresh tissues.

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Identification and analysis correlation between hub genes and immune cell infiltration related to LPS-induced cognitive impairment

Qiang,

Deng,

Song

et al. 2024

Heliyon

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Elevated serum levels of C-X-C motif chemokine ligand 10 can distinguish systemic lupus erythematosus patients from cutaneous lupus erythematosus patients

Cited by 3 publications

References 5 publications

Triple‐threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL‐lpr mice

Triple‐threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL‐lpr mice

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Identification and analysis correlation between hub genes and immune cell infiltration related to LPS-induced cognitive impairment

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