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

Kalthoum Tizaoui^1,*, Jae Won Yang^2,*, 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 Koyanagi^6,7, Louis Jacob^6,8, Seoyeon Park⁴, Jae Il Shin^3✉, Lee Smith^9✉

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.

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Citation:
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 https://www.ijbs.com/v18p3731.htm

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