Int J Biol Sci 2022; 18(9):3731-3746. doi:10.7150/ijbs.67587 This issue


The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review

Kalthoum Tizaoui1,*, Jae Won Yang2,*, Keum Hwa Lee3, Ji Hong Kim3, Minseok Kim4, Sojung Yoon4, Yeonwoo Jung4, Joon Beom Park4, Kitae An4, Hyeok Choi4, Donggyu Song4, HyunTaek Jung4, Seongmin Ahn4, Taeho Yuh4, Hee Min Choi4, Jae Ha Ahn4, Younjuong Kim4, Sanghyun Jee4, Hyeongsun Lee4, Soohwa Jin4, Jun-Gu Kang4, Bohyun Koo4, Joo Yeop Lee4, Kyoung Min Min4, Wonseok Yoo4, Hyeong Jun Rhyu4, Yeonjung Yoon4, Min Ho Lee4, Sung Eun Kim4, Jimin Hwang5, Ai Koyanagi6,7, Louis Jacob6,8, Seoyeon Park4, Jae Il Shin3✉, Lee Smith9✉

1. Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia.
2. Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
3. Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
4. Yonsei University College of Medicine, Seoul, Republic of Korea.
5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
6. Parc Sanitari Sant Joan de Deu/CIBERSAM, ISCIII, Universitat de Barcelona, Fundacio Sant Joan de Deu, Sant Boi de Llobregat, Barcelona, Spain.
7. ICREA, Pg. Lluis Companys 23, Barcelona, Spain.
8. Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.
9. The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Tizaoui K, Yang JW, Lee KH, Kim JH, Kim M, Yoon S, Jung Y, Park JB, An K, Choi H, Song D, Jung H, Ahn S, Yuh T, Choi HM, Ahn JH, Kim Y, Jee S, Lee H, Jin S, Kang JG, Koo B, Lee JY, Min KM, Yoo W, Rhyu HJ, Yoon Y, Lee MH, Kim SE, Hwang J, Koyanagi A, Jacob L, Park S, Shin JI, Smith L. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review. Int J Biol Sci 2022; 18(9):3731-3746. doi:10.7150/ijbs.67587. Available from

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Graphic abstract

YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.

Keywords: YKL-40, Autoimmune disease, Pathogenesis, Diagnostic marker, Biomarker