Multidimensional immune profiling of cutaneous lupus erythematosus in vivo stratified by patient responses to antimalarials
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Title: Multidimensional immune profiling of cutaneous lupus erythematosus in vivo stratified by patient responses to antimalarials Jay Patel1,2†; Thomas Vazquez1,2†; Felix Chin1,2; Emily Keyes1,2; Daisy Yan, MD1,2; DeAnna Diaz1,2; Madison Grinnell1,2; Meena Sharma, PhD1,2; Yubin Li, PhD1,2; Rui Feng, PhD3; Grant Sprow1,2; Victoria P. Werth, MD1,2* 1Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104 2Department of Dermatology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 3 Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA † These authors contributed equally Abstract: Objective: The pathogenesis of cutaneous lupus erythematous (CLE) is multifactorial and CLE is difficult to treat due to heterogeneity of inflammatory processes between patients. Antimalarials such as hydroxychloroquine (HCQ) and quinacrine (QC) have long been first-line systemic therapy; however, many patients do not respond and require systemic immunosuppressants with undesirable side effects. Given the complexity and unpredictable responses in CLE, we sought to identify the immunologic landscape of CLE patients stratified by subsequent treatment outcomes to identify potential biomarkers of inducible response. Method: We performed imaging mass cytometry with 48 treatment-naïve skin biopsies of HCQ responders, QC responders, and non-responders (NR) to analyze multiple immune cell types and inflammatory markers in their native environment in CLE skin. Patients were stratified according to their subsequent response to antimalarials to identify baseline immunophenotypes which may predict response to therapy. Results: HCQ responders demonstrated increased CD4 T cells compared to QC. NR had decreased Tregs compared to QC and increased central memory T cells compared to HCQ. QC responders expressed increased phosphorylated (p) STING and IFNκ compared to HCQ. pSTING and IFNκ localized to conventional dendritic cells and positively correlated on a tissue and cellular level. Neighborhood analysis revealed decreased regulatory cell interactions in NR patients. Hierarchical clustering revealed NR groups separated based on pSTAT2/3/4/5, pIRF3, Granzyme B, pJAK2, IL4, IL17, and IFNγ. Conclusion: These findings demonstrate differential immune compositions between CLE patients, guiding the future for precision-based medicine and treatment response
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Files are provided as .mcd requiring extraction to TIFF with MCD Viewer. ROI1 equivalent to Panel 1 ROI2 equivalent to Panel 2 TIFF images may be segmented and imported into histocat for single cell analysis. See Materials and Methods: Title: Multidimensional immune profiling of cutaneous lupus erythematosus in vivo stratified by patient responses to antimalarials Jay Patel1,2†; Thomas Vazquez1,2†; Felix Chin1,2; Emily Keyes1,2; Daisy Yan, MD1,2; DeAnna Diaz1,2; Madison Grinnell1,2; Meena Sharma, PhD1,2; Yubin Li, PhD1,2; Rui Feng, PhD3; Grant Sprow1,2; Victoria P. Werth, MD1,2*