YIM-O13. Development of novel protein biomarkers for the prediction of response to treatment in juvenile idiopathic arthritis

Abstract Background Oligo-articular juvenile idiopathic arthritis (Oligo JIA) is the most common subtype of juvenile idiopathic arthritis. Intra-articular corticosteroid (IAC) injection is a mainstay treatment of oligo JIA providing pain relief, improving mobility and preventing further joint destruction in the majority of patients. In 2015, production of triamcinolone hexacetonide (TH) an intra-articular corticosteroid was discontinued in the United States leading to use of triamcinolone acetonide (TA) as an alternative. In this study, we compared response to treatment in children with oligo JIA who underwent therapy with intra-articular TA and TH injection. Methods Our study is a retrospective chart review of children with oligo JIA who were treated with IAC injections with TH between January 2012 and June 2015 and TA between J uly 2015 and December 2018. The two groups were followed at John R. Oishei Children’s Hospital of Buffalo and were evaluated for response to treatment, side effects and predictors of response including duration of disease before treatment, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Response to treatment was defined as at least 6 months follow up without evidence of active arthritis in injected joints. Patients were considered to be non-responders if they continued to show active arthritis during their first follow up after joint injection. The primary objective was to evaluate whether there was a significant difference in rate of response between TH and TA. Results Forty-nine patients, 38 female and 11 male with oligo JIA were included in the study. The average age was 6.7 years. A total of 111 joints were injected includin g 78 knees, 13 ankles, 9 wrists, 4 hips, 4 elbows, 2 TMJ and one subtalar joint. In the TA group, 49% (29/59) did not show response to injection compared to 27% (14/52) in the TH group. After 6 months, response rates were better for individuals injected with TH compared to TA (73% vs. 51%). In general, response to intra-articular TH was superior to TA with P = .016 using chi-square test of independence. This difference in outcome was not influenced by other variables such as duration of illness before treatment (P value 0.784) or elevated ESR and CRP. No difference in side effects between the two groups were noted. Conclusion Our results in conjunction with prior published data suggests that TH intra-articular joint injection in oligo JIA is superior to TA, although future controlled trials are necessary for confirmation. An effective, long lasting treatment can have a great impact on the outcome of these children.

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Abstract 14727: Meteorin-like Glial Cell Differentiation Regulator is a Novel Protein Biomarker of Cardiovascular Outcomes in Patients With Diabetes and Vascular Disease: A TECOS Substudy

Circulation ◽

10.1161/circ.142.suppl_3.14727 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lauren K Truby ◽

Jessica A Regan ◽

Maggie Nguyen ◽

Stephani Giamberardino ◽

Robert J Mentz ◽

...

Keyword(s):

Heart Failure ◽

Conditional Logistic Regression ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Specific Protein ◽

Cardiovascular Outcomes ◽

Diabetic Patients ◽

Proteomic Profiling ◽

Protein Biomarkers ◽

Novel Protein

Introduction: To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM). Hypothesis: Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with DM. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling (>700 proteins) on 440 paired cases and matched controls from placebo-assigned participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Cases were defined as having met the primary composite outcome of MACE or incident HFH and matched to controls on baseline prevalent heart failure, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Conditional logistic regression was used to determine the association between log-transformed relative protein expression and incident MACE or HFH. False-discovery-rate (FDR) was used to adjust for multiple comparisons. Results: We identified three specific proteins that were significantly associated with prevalent MACE or HFH: METRNL, Notch 3, and ROR1 (OR 2.1, 1.6, 1.7 and q-value 0.01, 0.02, and 0.05 respectively) (Figure 1). METRNL, in particular, performed similarly to the established biomarker NT-proBNP (Figure 1). When MACE and HFH were analyzed separately, METRNL, in particular, remained strongly associated with both outcomes (OR 2.0, p<0.001 and OR 2.7, p=0.05). Conclusions: Three novel protein biomarkers, in particular METRNL (a circulating adipokine that regulates insulin-sensitivity), may identify diabetic patients at high risk for subsequent HF and MACE. Additional studies are needed to replicate these findings and uncover the biologic mechanism linking adipokine signaling and heart failure.

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Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau

Neuropsychopharmacology ◽

10.1038/s41386-020-00840-3 ◽

2020 ◽

Vol 46 (1) ◽

pp. 98-115 ◽

Cited By ~ 2

Author(s):

Sruti Rayaprolu ◽

Lenora Higginbotham ◽

Pritha Bagchi ◽

Caroline M. Watson ◽

Tian Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Network ◽

Protein Biomarkers ◽

Cellular Processes ◽

Complex Protein ◽

Underlying Mechanisms ◽

Novel Protein

AbstractThe repeated failures of amyloid-targeting therapies have challenged our narrow understanding of Alzheimer’s disease (AD) pathogenesis and inspired wide-ranging investigations into the underlying mechanisms of disease. Increasing evidence indicates that AD develops from an intricate web of biochemical and cellular processes that extend far beyond amyloid and tau accumulation. This growing recognition surrounding the diversity of AD pathophysiology underscores the need for holistic systems-based approaches to explore AD pathogenesis. Here we describe how network-based proteomics has emerged as a powerful tool and how its application to the AD brain has provided an informative framework for the complex protein pathophysiology underlying the disease. Furthermore, we outline how the AD brain network proteome can be leveraged to advance additional scientific and translational efforts, including the discovery of novel protein biomarkers of disease.

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Identification of Novel Protein Biomarkers of Preterm Birth in Human Cervical−Vaginal Fluid

Journal of Proteome Research ◽

10.1021/pr0605421 ◽

2007 ◽

Vol 6 (4) ◽

pp. 1269-1276 ◽

Cited By ~ 78

Author(s):

Leonardo Pereira ◽

Ashok P. Reddy ◽

Thomas Jacob ◽

Archana Thomas ◽

Kimberly A. Schneider ◽

...

Keyword(s):

Preterm Birth ◽

Vaginal Fluid ◽

Protein Biomarkers ◽

Novel Protein

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Molecular biomarkers for prediction of response to treatment and survival in triple negative breast cancer patients from Egypt

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2015.07.014 ◽

2015 ◽

Vol 99 (2) ◽

pp. 303-311 ◽

Cited By ~ 14

Author(s):

Abeer Bahnassy ◽

Marwa Mohanad ◽

Manal F. Ismail ◽

Sabry Shaarawy ◽

Ahmed El-Bastawisy ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Biomarkers ◽

Response To Treatment ◽

Breast Cancer Patients ◽

Prediction Of Response

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Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

Clinical Science ◽

10.1042/cs20130301 ◽

2014 ◽

Vol 126 (12) ◽

pp. 857-867 ◽

Cited By ~ 16

Author(s):

Hui-juan Wang ◽

Bao-zeng Wang ◽

Peng-jun Zhang ◽

Jie Deng ◽

Zhi-rui Zhao ◽

...

Keyword(s):

Serum Protein ◽

Sofa Score ◽

Predictive Value ◽

Mirna Target ◽

Target Genes ◽

Apache Ii Score ◽

Protein Biomarkers ◽

Combined Analysis ◽

Better Than ◽

Novel Protein

Four novel protein biomarkers encoded by the miRNA target genes were identified for patients with sepsis. The combined analysis of the four proteins indicated that their predictive value for sepsis prognosis was better than the values for the SOFA score and APACHE II score.

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Prediction of Response to Treatment with Lenalidomide in Patients with Non-Del 5q Myelodysplastic Syndrome by Gene Expression Profiling Remains Difficult.

Blood ◽

10.1182/blood.v114.22.2781.2781 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2781-2781

Author(s):

Wolf-Karsten Hofmann ◽

Florian Nolte ◽

Ouidad Benlasfer ◽

Eckhard Thiel ◽

Gerhard Ehninger ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Clinical Response ◽

Expression Profiling ◽

Research Funding ◽

Bone Marrow Cells ◽

Response To Treatment ◽

Specific Gene ◽

Prediction Of Response

Abstract Abstract 2781 Poster Board II-757 Lenalidomide belongs to a proprietary class of immunmodulatory drugs showing therapeutic activity in patients with myelodysplastic syndrome (MDS), in particular in those having the 5q-abnormality, but also in patients not showing this cytogenetical aberration. In 2008, Ebert et al. (PLos Med. 2, e35) could demonstrate that there is a specific gene expression profile in bone marrow cells collected from MDS-patients either with 5q- syndrome as well as MDS-patients having no 5q-abnormality which is strongly correlated with the clinical response to treatment with lenalidomide. Whereas this finding is not of clinical importance in patients with MDS del 5q (overall response 75 %) it may play a pivotal role for prediction of clinical response to lenalidomide in non-del 5q MDS-patients. Therefore, we have studied gene expression profile (HG-U133plus2.0, Affymetrix, Santa Clara, CA) of routinely isolated low-density mononuclear bone marrow cells from 8 patients with IPSS low/int-1 risk MDS having no deletion on chromosome 5 but were subsequently treated with lenalidomide 5 mg/day. All of the patients were transfusion dependent for red blood cells. The median duration of treatment with lenalidomide was 22 weeks. RNA was extracted by Trizol and quality controlled by using a Bioanalyzer 2100 system (Agilent, Waldborn, Germany) to exclude RNA degradation. Microarray hybridization was performed according to the standard Affymetrix protocol. Data were analyzed by Microarray Analysis Suites 5.0 (MAS 5.0; Affymetrix) and GeneSpring (Agilent Technologies, Santa Clara, CA). For clustering analysis we utilized the gene list of 68 discriminating genes as published by Ebert et al. the molecular analysis did clearly separate two groups of patients having specific gene expression profiles according to the responder/non-responder group as published previously. Furthermore, single sample prediction could discriminate three out of 8 patients to be possible responders to lenalidomide but this was not correlated to the clinical course of those patients while on treatment with lenalidomide. However, none of the MDS-patients receiving lenalidomide did show significant clinical response as defined by reduction of transfusion requirement by 50 % or transfusion independence. In conclusion, prediction of response to lenalidomide in non-del 5q patients by gene expression profiling so far remains critical. Prospective analysis of molecular changes including DNA analysis in larger clinical trials using lenalidomide in non-del 5q MDS-patients are required to establish reliable predictive markers in MDS. Disclosures: Hofmann: Celgene: Research Funding. Platzbecker:Celgene: Research Funding.

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