Publications by authors named "Jessica L Turnier"

8 Publications

  • Page 1 of 1

Using autoantibody signatures to define cancer risk in dermatomyositis.

J Clin Invest 2022 Jan;132(2)

Department of Internal Medicine, Division of Rheumatology.

Dermatomyositis is an idiopathic inflammatory myopathy with a highly heterogeneous disease course. Although there is a known increase in cancer risk surrounding the time of dermatomyositis diagnosis, the mechanisms driving this increased risk are not well understood. Further, there are no current standardized cancer screening guidelines for dermatomyositis patients. In this issue of the JCI, Fiorentino, Mecoli, et al. discovered additional autoantibodies in patients with dermatomyositis and anti-TIF1-γ autoantibodies, a known risk factor for malignancy. They observed a decreased cancer risk with an increasing number of autoantibodies. Importantly, these findings indicate that more detailed autoantibody phenotyping at diagnosis might better predict cancer risk and also suggest that diversity and kinetics of the host immune response might influence cancer development.
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http://dx.doi.org/10.1172/JCI156025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759773PMC
January 2022

Non-invasive tape-stripping with high-resolution RNA profiling effectively captures a pre-inflammatory state in nonlesional psoriatic skin.

J Invest Dermatol 2021 Nov 19. Epub 2021 Nov 19.

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address:

Tape stripping is a minimally invasive, non-scarring method that can be utilized to assess gene expression in skin but is infrequently used given technical constraints. By comparing different tape stripping technologies and full thickness skin biopsy results of lesional and non-lesional psoriatic skin from the same patients, we demonstrate that tape stripping with optimized high-resolution transcriptomic profiling can be used to effectively assess and characterize inflammatory responses in skin. Upon comparison with single-cell RNA-seq data from psoriatic full thickness skin biopsies, we illustrate that tape-stripping efficiently captures the transcriptome of the upper layers of the epidermis with sufficient resolution to assess the molecular components of the feed-forward immune amplification pathway in psoriasis. Notably, non-lesional psoriatic skin sampled by tape stripping demonstrates activated, pro-inflammatory changes when compared to healthy control skin, suggesting a pre-psoriatic state, which is not captured on full-thickness skin biopsy transcriptome profiling. This work illustrates an approach to assess inflammatory response in the epidermis by combining non-invasive sampling with high throughput RNA sequencing, providing a foundation for biomarker discoveries and mechanism of action studies for inflammatory skin conditions.
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http://dx.doi.org/10.1016/j.jid.2021.09.038DOI Listing
November 2021

Comparison of Lesional Juvenile Myositis and Lupus Skin Reveals Overlapping Yet Unique Disease Pathophysiology.

Arthritis Rheumatol 2021 06 2;73(6):1062-1072. Epub 2021 May 2.

University of Michigan, Ann Arbor.

Objective: Skin inflammation heralds systemic disease in juvenile myositis, yet we lack an understanding of pathogenic mechanisms driving skin inflammation in this disease. We undertook this study to define cutaneous gene expression signatures in juvenile myositis and identify key genes and pathways that differentiate skin disease in juvenile myositis from childhood-onset systemic lupus erythematosus (SLE).

Methods: We used formalin-fixed paraffin-embedded skin biopsy samples from 15 patients with juvenile myositis (9 lesional, 6 nonlesional), 5 patients with childhood-onset SLE, and 8 controls to perform transcriptomic analysis and identify significantly differentially expressed genes (DEGs; q ≤ 5%) between patient groups. We used Ingenuity Pathway Analysis (IPA) to highlight enriched biologic pathways and validated DEGs by immunohistochemistry and quantitative real-time polymerase chain reaction.

Results: Comparison of lesional juvenile myositis to control samples revealed 221 DEGs, with the majority of up-regulated genes representing interferon (IFN)-stimulated genes. CXCL10, CXCL9, and IFI44L represented the top 3 DEGs (fold change 23.2, 13.3, and 13.0, respectively; q < 0.0001). IPA revealed IFN signaling as the top canonical pathway. When compared to childhood-onset SLE, lesional juvenile myositis skin shared a similar gene expression pattern, with only 28 unique DEGs, including FBLN2, CHKA, and SLURP1. Notably, patients with juvenile myositis who were positive for nuclear matrix protein 2 (NXP-2) autoantibodies exhibited the strongest IFN signature and also demonstrated the most extensive Mx-1 immunostaining, both in keratinocytes and perivascular regions.

Conclusion: Lesional juvenile myositis skin demonstrates a striking IFN signature similar to that previously reported in juvenile myositis muscle and peripheral blood. Further investigation into the association of a higher IFN score with NXP-2 autoantibodies may provide insight into disease endotypes and pathogenesis.
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http://dx.doi.org/10.1002/art.41615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274390PMC
June 2021

The Role of Cutaneous Type I IFNs in Autoimmune and Autoinflammatory Diseases.

J Immunol 2020 12;205(11):2941-2950

Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109

IFNs are well known as mediators of the antimicrobial response but also serve as important immunomodulatory cytokines in autoimmune and autoinflammatory diseases. An increasingly critical role for IFNs in evolution of skin inflammation in these patients has been recognized. IFNs are produced not only by infiltrating immune but also resident skin cells, with increased baseline IFN production priming for inflammatory cell activation, immune response amplification, and development of skin lesions. The IFN response differs by cell type and host factors and may be modified by other inflammatory pathway activation specific to individual diseases, leading to differing clinical phenotypes. Understanding the contribution of IFNs to skin and systemic disease pathogenesis is key to development of new therapeutics and improved patient outcomes. In this review, we summarize the immunomodulatory role of IFNs in skin, with a focus on type I, and provide insight into IFN dysregulation in autoimmune and autoinflammatory diseases.
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http://dx.doi.org/10.4049/jimmunol.2000596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694882PMC
December 2020

Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis activity.

Rheumatology (Oxford) 2019 02;58(2):321-330

Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objectives: We used an unbiased proteomics approach to identify candidate urine biomarkers (CUBMs) predictive of LN chronicity and pursued their validation in a larger cohort.

Methods: In this cross-sectional pilot study, we selected urine collected at kidney biopsy from 20 children with varying levels of LN damage (discovery cohort) and performed proteomic analysis using isobaric tags for relative and absolute quantification (iTRAQ). We identified differentially excreted proteins based on degree of LN chronicity and sought to distinguish markers exhibiting different relative expression patterns using hierarchically clustered log10-normalized relative abundance data with linked and distinct functions by biological network analyses. For each CUBM, we performed specific ELISAs on urine from a validation cohort (n = 41) and analysis of variance to detect differences between LN chronicity, with LN activity adjustment. We evaluated for CUBM expression in LN biopsies with immunohistochemistry.

Results: iTRAQ detected 112 proteins in urine from the discovery cohort, 51 quantifiable in all replicates. Simple analysis of variance revealed four differentially expressed, chronicity-correlated proteins (P-values < 0.05). Further correlation and network analyses led to selection of seven CUBMs for LN chronicity. In the validation cohort, none of the CUBMs distinguished LN chronicity degree; however, urine SERPINA3 demonstrated a moderate positive correlation with LN histological activity. Immunohistochemistry further demonstrated SERPINA3 staining in proximal tubular epithelial and endothelial cells.

Conclusion: We identified SERPINA3, a known inhibitor of neutrophil cathepsin G and angiotensin II production, as a potential urine biomarker to help quantify LN activity.
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http://dx.doi.org/10.1093/rheumatology/key301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343468PMC
February 2019

Urine S100 proteins as potential biomarkers of lupus nephritis activity.

Arthritis Res Ther 2017 Oct 24;19(1):242. Epub 2017 Oct 24.

Department of Rheumatology, Cincinnati Children's Hospital Medical Center, MLC 4010, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

Background: Improved, noninvasive biomarkers are needed to accurately detect lupus nephritis (LN) activity. The purpose of this study was to evaluate five S100 proteins (S100A4, S100A6, S100A8/9, and S100A12) in both serum and urine as potential biomarkers of global and renal system-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE).

Methods: In this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy control subjects using commercial enzyme-linked immunosorbent assays. Patients were divided into cohorts on the basis of biospecimen availability: (1) longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, and (4) cross-sectional urine. Global and renal disease activity were defined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K renal domain score. Nonparametric testing was used for statistical analysis, including the Wilcoxon signed-rank test, Kruskal-Wallis test, Mann-Whitney U test, and Spearman's rank correlation coefficient.

Results: All urine S100 proteins were elevated in patients with active LN compared with patients with active extrarenal disease and healthy control subjects. All urine S100 protein levels decreased with LN improvement, with S100A4 demonstrating the most significant decrease. Urine S100A4 levels were also higher with proliferative LN than with membranous LN. S100A4 staining in the kidney localized to mononuclear cells, podocytes, and distal tubular epithelial cells. Regardless of the S100 protein tested, serum levels did not change with cSLE improvement.

Conclusions: Higher urine S100 levels are associated with increased LN activity in cSLE, whereas serum S100 levels do not correlate with disease activity. Urine S100A4 shows the most promise as an LN activity biomarker, given its pronounced decrease with LN improvement, isolated elevation in urine, and positive staining in resident renal cells.
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http://dx.doi.org/10.1186/s13075-017-1444-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655804PMC
October 2017

Tocilizumab for treating juvenile idiopathic arthritis.

Expert Opin Biol Ther 2016 27;16(4):559-66. Epub 2016 Feb 27.

a Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , University of Cincinnati College of Medicine , Cincinnati , OH , USA.

Introduction: Based on the known relevance of IL-6 in juvenile idiopathic arthritis (JIA) pathophysiology, tocilizumab has been investigated and approved for use in the treatment of systemic and polyarticular JIA. Tocilizumab is a humanized monoclonal antibody that inhibits signaling through both membrane bound and soluble IL-6R.

Areas Covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of tocilizumab in JIA and to provide our opinion on the place of tocilizumab in current treatment regimens. A literature search for all relevant clinical trials and studies with regards to tocilizumab, JIA and IL-6 was performed through PubMed, in addition to a review of recent conference abstracts.

Expert Opinion: Tocilizumab has an important and evolving role in controlling disease activity in patients with JIA. It has proven useful even in patients whose JIA has previously been refractory to other biologic disease modifying anti-rheumatic drugs (DMARDs) and also appears quite effective as monotherapy. Tocilizumab is relatively well tolerated amongst JIA patients, with systemic JIA patients experiencing more serious adverse events overall.
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http://dx.doi.org/10.1517/14712598.2016.1150997DOI Listing
October 2016

Concurrent Respiratory Viruses and Kawasaki Disease.

Pediatrics 2015 Sep 24;136(3):e609-14. Epub 2015 Aug 24.

Sections of Infectious Diseases, and

Background: The diagnosis of Kawasaki disease (KD) remains challenging without a definitive diagnostic test and currently is guided by using clinical patient characteristics and supported by laboratory data. The role of respiratory viruses in the pathogenesis of KD is not fully understood.

Methods: Charts of patients with KD admitted to Children's Hospital Colorado from January 2009 to May 2013 were retrospectively reviewed. Patients with KD who had a nasopharyngeal wash submitted for multiplex polymerase chain reaction (PCR) viral testing were included. Clinical characteristics, laboratory data, and outcomes of patients with and without positive respiratory viral PCR results were compared.

Results: Of 222 patients with KD admitted to the hospital, 192 (86%) had a respiratory viral PCR test performed on or shortly after admission. Ninety-three (41.9%) of the 192 patients with KD had a positive respiratory viral PCR, and the majority were positive for rhinovirus/enterovirus. No statistically significant differences were found in the clinical characteristics and laboratory values between the groups with and without positive respiratory viral PCR findings. Both groups had the same frequency of upper respiratory and gastrointestinal symptoms and had the same incidence of admission to the PICU, intravenous immunoglobulin-resistant disease, and coronary artery lesions.

Conclusions: No differences in clinical presentations or outcomes in children with KD stratified according to positive or negative respiratory viral PCR testing were observed. A positive respiratory viral PCR or presence of respiratory symptoms at the time of presentation should not be used to exclude a diagnosis of KD.
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http://dx.doi.org/10.1542/peds.2015-0950DOI Listing
September 2015
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