Chitinase-3-like Protein 1 (YKL-40): A New Biomarker of Inflammation in Pyoderma Gangrenosum
Keywords:pyoderma gangrenosum, chitinase-3-like protein 1, YKL-40, biomarker, inflammation
Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis with unclear aetiopathology, considered as an autoinflammatory disease, associated with other immune-mediated disorders. Chitinase-3-like protein 1 (YKL-40) is an inflammatory biomarker secreted by a wide variety of cells, including neutrophils. To evaluate YKL-40 serum level in relation to clinicopathological data, 48 patients with PG and 40 healthy controls were enrolled in the study. Skin lesions were measured to calculate the affected area. Inflammatory parameters (C-reactive protein, white blood cell count with neutrophils) were determined from blood samples. YKL-40 and IL-6 levels were measured in serum by enzyme-linked immunosorbent assay. YKL-40 serum level was significantly higher in patients with PG than in controls (58.4 vs 36.4 ng/ml, respectively; p < 0.00001). The positive correlation between YKL-40 level and IL-6 level was observed (r=0.48, p = 0.0006) along with a trend towards significance of relationship between YKL-40 level and C-reactive protein (r=0.28, p = 0.052). YKL-40 can be considered a valuable biomarker of inflammation in PG.
Ruocco E, Sangiuliano S, Gravina A, Miranda A, Nicoletti G. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatology Venereol 2009; 23: 1008-1017.
Ahronowitz I, Harp J, Shinkai K. Etiology and management of pyoderma gangrenosum: A comprehensive review. Am J Clin Dermatol 2012; 13: 191-211.
Adachi Y, Kindzelskii AL, Cookingham G, Shaya S, Moore EC, Todd 3rd RF, et al. Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenesum. J Invest Dermatol 1998; 111: 259-268.
Satoh TK, Mellett M, Contassot E, French LE. Are neutrophilic dermatoses autoinflammatory disorders? Br J Dermatol 2018; 178: 603-613.
Marzano AV, Ortega-Loayza AG, Heath M, Morse D, Genovese G, Cugno M. Mechanisms of inflammation in neutrophil-mediated skin diseases. Front Immunol 2019; 10: 1059.
Ashchyan HJ, Nelson CA, Stephen S, James WD, Micheletti RG, Rosenbach M. Neutrophilic dermatoses: pyoderma gangrenosum and other bowel- and arthritis-associated neutrophilic dermatoses. J Am Acad Dermatol 2018; 79: 1009-1022.
Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inﬂammation, tissue remodelling, ﬁbroses and cancer. Dan Med Bull 2006; 53: 172-209.
Hakala BE, White C, Recklies AD. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 1993; 268: 25803-25810.
Shackelton LM, Mann DM, Millis AJ. Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodeling. J Biol Chem 1995; 270: 13076-13083.
Volck B, Price PA, Johansen JS, Sørensen O, Benfield TL, Nielsen HJ, et al. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Physicians 1998; 110: 351-360.
Renkema GH, Boot RG, Au FL, Donker-Koopman WE, Strijland A, Muijsers AO, et al. Chitotriosidase a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. Eur J Biochem 1998; 251: 504-509.
Zhao T, Su Z, Li Y, Zhang X, You Q. Chitinase-3 like-protein-1 function and its role in diseases. Signal Transduct Target Ther 2020; 5: 201.
Johansen JS, Olee T, Price PA, Hashimoto S, Ochs RL, Lotz M. Regulation of YKL-40 production by human articular chondrocytes. Arthritis Rheum 2001; 44: 826-837.
Kzhyshkowska J, Mamidi S, Gratchev A, Kremmer E, Schmuttermaier C, Krusell L, et al. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Blood 2006; 107: 3221-3228.
De Ceuninck F, Pastoureau P, Bouet F, Bonnet J, Vanhoutte PM. Purification of guinea pig YKl40 and modulation of its secretion by cultured articular chondrocytes. J Cell Biochem 1998; 69: 414-424.
Millis AJ, Hoyle M, Reich E, Mann DM. Isolation and characterization of a Mr = 38,000 protein from differentiating smooth muscle cells. J Biol Chem 1985; 260: 3754-3761.
Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang M-J, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol 2011; 73: 479-501.
Prakash M, Bodas M, Prakash D, Nawani N, Khetmalas M, Mandal A, et al. Diverse pathological implications of YKL-40: answers may lie in 'outside-in' signaling. Cell Signal 2013; 25: 1567-1573.
Kastrup J. Can YKL-40 be a new inflammatory biomarker in cardiovascular disease? Immunobiology 2012; 217: 483-491.
Roslind A, Johansen JS. YKL-40: a novel marker shared by chronic inflammation and oncogenic transformation. Methods Mol Biol 2009; 511: 159-184.
Jockenhöfer F, Wollina U, Salva KA, Benson S, Dissemond J. The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum. Br J Dermatol 2019; 180: 615-620.
Koutroubakis IE, Petinaki E, Dimoulios P, Vardas E, Roussomoustakaki M, Maniatis AN, et al. Increased serum levels of YKL-40 in patients with inflammatory bowel disease. Int J Colorectal Dis 2003; 18: 254-259.
Erzin Y, Uzun H, Karatas A, Celik AF. Serum YKL-40 as a marker of disease activity and stricture formation in patients with Crohn's disease. J Gastroenterol Hepatol 2008; e357-e362.
Bernardi D, Podswiadek M, Zaninotto M, Punzi L, Plebani M. YKL-40 as a marker of joint involvement in inflammatory bowel disease. Clin Chem 2003; 49: 1685-1688.
Kazakova MH, Batalov AZ, Mateva NG, Kolarov ZG, Sarafian VS. YKL-40 and cytokines - a new diagnostic constellation in rheumatoid arthritis? Folia Med (Plovdiv) 2017; 59: 37-42.
Hirata S, Tanaka Y. Assessment of disease activity in rheumatoid arthritis by multi-biomarker disease activity (MBDA) score. Nihon Rinsho Meneki Gakkai Kaishi 2016; 39: 37-41.
Peltomaa R, Paimela L, Harvey S, Helve T, Leirisalo-Repo M. Increased level of YKL-40 in sera from patients with early rheumatoid arthritis: a new marker for disease activity. Rheumatol Int 2001; 20: 192-196.
Kazakova M, Batalov A, Deneva T, Mateva N, Kolarov Z, Sarafian V. Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. Rheumatol Int 2013; 33: 341-346.
Zivanović S, Rackov LP, Vojvodić D, Vucetić D. Human cartilage glycoprotein 39 - biomarker of joint damage in knee osteoarthritis. Int Orthop 2009; 33: 1165-1170.
Brahe CH, Dehlendorff C, Østergaard M, Johansen JS, Ørnbjerg LM, Hørslev-Petersen K, et al. Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis: post-hoc explorative and validation studies based on the CIMESTRA and OPERA trials. Scand J Rheumatol 2018; 47: 259-269.
Salomon J, Piotrowska A, Matusiak Ł, Dzięgiel P, Szepietowski JC. Chitinase-3-like protein 1 (YKL-40) is expressed in lesional skin in hidradenitis suppurativa. In Vivo 2019; 33: 141-143.
Matusiak Ł, Salomon J, Nowicka-Suszko D, Bieniek A, Szepietowski JC. Chitinase-3-like protein 1 (YKL-40): novel biomarker of hidradenitis suppurativa disease activity? Acta Derm Venereol 2015; 95: 736-737.
Ebrahim A, Mustafa AI, El-Shimi OS, Fathy MA. Serum YKL40: A novel potential link between inflammation and dyslipidemia in acne vulgaris. J Cosmet Dermatol 2020; 19: 1219-1223.
Salomon J, Matusiak Ł, Nowicka-Suszko D, Szepietowski JC. Chitinase-3-like protein 1 (YKL-40) is a biomarker of severity of joint involvement in psoriatic arthritis. Adv Dermatol Allergol 2018; 35: 485-489.
Boyd TA, Eastman PS, Huynh DH, Qureshi F, Sasso EH, Bolce R, et al. Correlation of serum protein biomarkers with disease activity in psoriatic arthritis. Expert Rev Clin Immunol 2020; 16: 335-341.
Seo J, Ahn Y, Zheng Z, Kim BO, Choi MJ, Bang D, et al. Clinical significance of serum YKL-40 in Behçet disease. Br J Dermatol 2016; 174: 1337-1344.
Chen C, Liang Y, Zhang Z, Zhang Z, Yang Z. Relationships between increased circulating YKL-40, IL-6 and TNF-α levels and phenotypes and disease activity of primary Sjögren's syndrome. Int Immunopharmacol 2020; 88: 106878.
Nielsen AR, Plomgaard P, Krabbe KS, Johansen JS, Pedersen BK. IL-6, but not TNF-α, increases plasma YKL-40 in human subjects. Cytokine 2011; 55: 152-155.
Vind I, Johansen JS, Price PA, Munkholm P. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease. Scand J Gastroenterol 2003; 38: 599-605.
Salomon J, Matusiak L, Nowicka-Suszko D, Szepietowski JC. Chitinase-3-like protein 1 (YKL-40) is a new biomarker of inflammation in psoriasis. Mediators Inflamm 2017; 2017: 9538451.
How to Cite
Copyright (c) 2021 Alina Jankowska-Konsur, Magdalena Łyko, Klaudia Rubas, Danuta Nowicka-Suszko, Joanna Maj, Jacek C. Szepietowski
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.