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431 Galectin-3 as a Biomarker and Potential Therapeutic Target in Biliary Atresia
- Dor Yoeli, Yuhuan Luo, Alexander Chaidez, Zhaohui Wang, Megan A. Adams, Christene A. Huang, Cara L. Mack, Nalu Navarro-Alvarez
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, p. 84
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OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p < 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p < 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p > 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.
4371 The Role of B Cells in Keloid Formation
- Jaclyn B Anderson, Alexander B Harrant, Nalu Navarro-Alvarez, Zhaohui Wang, Adrie van Bokhoven, Whitney High, Tae W Chong, Christene A. Huang
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 18-19
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OBJECTIVES/GOALS: Recent studies indicate B cells are involved in dermal fibroblast activation and collagen deposition in the skin. However, B cell distribution in epidermal and dermal layers is unknown. Here, We aim to characterize the distribution of B cells residing in normal skin and keloidal scars. METHODS/STUDY POPULATION: One abdominal normal skin sample and two keloid samples (ear and shoulder) were obtained from the University of Colorado Biorepository Core Facility and from the Plastic Surgery Clinics. Five micron sections from formalin-fixed paraffin-embedded samples were prepared for multiplex fluorescence immunohistochemistry by the Human Immunology & Immunotherapy Initiative. We stained for CD20+, CD19+, and DAPI. Slides were imaged using Vectra®3 scanning system from PerkinElmer. Images were analyzed in InForm®Tissue Finder, phenotpr, phenoptrReports by Akoya biosciences. RESULTS/ANTICIPATED RESULTS: We found a significant increase in the percentage of CD20+ and CD19+ B cells in keloid skin compared to normal skin tissue (14.50% and 14.20% vs 6.47% and 7.56% of the total cells), respectively. Interestingly, we found that in the epidermis of keloid skin CD20+ cell were more abundant (14.46%) whereas in the epidermis normal skin CD20+ cells were less predominant (5.14%). In the dermis of keloid skin, CD20+ and CD19+ were in equal proportions (13%) whereas in normal skin CD19+ cells were more predominant (10.44%) compared to CD20+ cells (7.04%). Dual positive B cells, CD19+/CD20+ cells, were more abundant in keloid dermis (11.06%) compared to normal skin dermis (1.24%). DISCUSSION/SIGNIFICANCE OF IMPACT: B cells are involved in fibroblast activation in diseases such as scleroderma and rheumatoid arthritis. With the increase of CD19+/CD20+ B cells in keloids, the role of B cells in keloid pathogenesis warrants further study. CD27 staining may determine if these are activated or follicular B cells.