Test Details
Methodology
Roche Diagnostics Electrochemiluminescence Immunoassay (ECLIA)
Use
This test is used for measurement of YKL-40 in EDTA plasma.
Limitations
This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.
Custom Additional Information
YKL-40 is a highly conserved glycoprotein product of the Chitinase-3-Like Protein 1 (CHI3L1) gene. YKL-40 is named after the three N-terminal amino acids (tyrosine (Y), lysine (K) and leucine (L)) and the protein’s molecular weight (40 kDa).1,2 YKL-40 can be secreted by various types of cells including macrophages, neutrophils, chondrocytes, synoviocytes, smooth muscle cells, fibroblast-like cells and tumor cells and may serve a role in apoptosis and remodeling or degradation of the extracellular matrix.2,3 Most prominently, YKL-40 levels positively correlate with inflammation that occurs in the setting of various diseases, including diabetes mellitus, inflammatory bowel disease (IBD), acute kidney injury, chronic kidney disease, rheumatoid arthritis (RA), Alzheimer’s disease (AD), multiple sclerosis (MS) and coronary artery disease.1-4
Given its broad presentation due to inflammation from a wide variety of diseases, YKL-40 can be considered a broadly applicable, highly-sensitive marker of inflammatory process associated with disease onset and activity throughout the body, unlike C-reactive protein (CRP), which is only produced by the liver. However, like Neurofilament light chain (NfL), that broad applicability necessitates a clinical context and symptomology for YKL-40 to be understood and interpreted. This means that YKL-40 is unlikely to be diagnostic for any particular disease, but rather YKL-40 levels can lend evidence toward a diagnosis of a variety of conditions within the context of the clinical workup or facilitate monitoring of therapeutic efficacy or disease status.
• RA disease and therapeutic monitoring: A meta-analysis5 of 11 studies of circulating YKL-40 levels6-14 concluded that measurements of YKL-40 are significantly higher in RA patients relative to healthy controls and that YKL-40 levels positively correlated with both RA disease activity and rheumatoid factor level. Another meta-analysis by Tizaoui et al. reported that nine studies15-20 showed YKL-40 can be used to monitor therapeutic efficacy as measured levels decreased in patients on treatment.
• Kidney transplant: In patients undergoing deceased donor kidney transplantation, lower levels of YKL-40 correlated with immediate graft function.21 Additionally, YKL-40 urine levels collected within hours of transplant predicted need for dialysis.21 In the event of delayed graft function, elevated donor urine YKL-40 concentration was associated with a lower risk of graft failure.22
• Colorectal cancer: A 2022 meta-analysis23 of nine studies24-32 employing blood YKL-40 measurements concluded that collectively the published literature shows that elevated YKL-40 levels is related to worse prognosis for patients and therefore might be useful as a reliable indicator throughout treatment and disease course.
• AD and dementia: In pre-clinical AD subjects, YKL-40, along with GFAP (glial fibrillary acid protein), were shown to be significantly elevated relative to healthy controls.33 More generally, in a study with groups of patients diagnosed with AD, frontotemporal dementia, Lewy body dementia, or vascular dementia, YKL-40 was significantly elevated in all groups relative to healthy controls34 and elevated plasma YKL-40 levels are associated with poorer cognition and lower brain volume.35
There have also been reported studies for the use of YKL-40 in MS, IBD and diabetic neuropathy, but the clinical data are not as conclusive.
Specimen Requirements
Specimen
Plasma (EDTA)
Volume
1 mL
Minimum Volume
0.7 mL (Note: This volume does not allow for repeat testing.)
Container
Lavender-top (EDTA) tube
Collection Instructions
Draw blood in lavender-top (EDTA) tube. Invert to mix with preservatives. Centrifuge and transfer to a labeled plastic transport tube.
Stability Requirements
| Termperature | Period |
|---|---|
| Room temperature | 14 days |
| Refrigerated | 14 days |
| Frozen | 14 days |
| Freeze/thaw cycles | Stable x3 |
Reference Range
| Age (years) | ng/mL |
| 0 to 19 y | Not established |
| 20 to 29 y | 0.0–39.2 |
| 30 to 39 y | 0.0–51.2 |
| 40 to 49 y | 0.0–66.6 |
| 50 to 59 y | 0.0–104.0 |
| 60 to 69 y | 0.0–196.0 |
| 70 to 79 y | 0.0–222.0 |
| >79 y | 0.0–396.0 |
Storage Instructions
Room temperature
Footnotes
1. Tizaoui K, Yang JW, Lee KH, et al. The Role of YKL-40 in the Pathogenesis of Autoimmune Diseases: A Comprehensive Review. Int J Biol Sci. 2022 May 21;18(9):3731-3746. PubMed 35813465
2. Liu D, Hu X, Ding X, Li M, Ding L. Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review. Int J Mol Sci. 2024 Dec 15;25(24):13437. PubMed 39769202
3. Blazevic N, Rogic D, Pelajic S, et al. YKL-40 as a Biomarker in Various Inflammatory Diseases: A Review. Biochem Med (Zagreb). 2024 Feb 15;34(1):010502. Epub 2023 Dec 15. PubMed 38125621
4. Kjaergaard AD, Johansen JS, Bojesen SE, Nordestgaard BG. Role of Inflammatory Marker YKL-40 in the Diagnosis, Prognosis and Cause of Cardiovascular and Liver Diseases. Crit Rev Clin Lab Sci. 2016 Dec;53(6):396-408. PubMed 27187575
5. Lee YH, Song GG. YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-Analysis. J Rheum Dis. 2019;26(4):257-263. doi.org/10.4078/jrd.2019.26.4.257
6. Turkyilmaz AK, Devrimsel G, Kirbas A, et al. Relationship between pulse wave velocity and serum YKL-40 level in patients with early rheumatoid arthritis. Rheumatol Int. 2013 Nov;33(11):2751-2756. PubMed 23797781
7. 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 Feb;33(2):341-346. PubMed 22451025
8. Nielsen KR, Steffensen R, Boegsted M, et al. Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects. Arthritis Res Ther. 2011 Jun 29;13(3):R109. PubMed 21714862
9. Johansen JS, Kirwan JR, Price PA, Sharif M. Serum YKL-40 concentrations in patients with early rheumatoid arthritis: relation to joint destruction. Scand J Rheumatol. 2001;30(5):297-304. PubMed 11727845
10. Janckila AJ, Neustadt DH, Yam LT. Significance of serum TRACP in rheumatoid arthritis. J Bone Miner Res. 2008 Aug;23(8):1287-1295. PubMed 18410226
11. Vos K, Steenbakkers P, Miltenburg AM, et al. Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2000 Jul;59(7):544-548. PubMed 10873965
12. Jafari-Nakhjavani MR, Ghorbanihaghjo A, Bagherzadeh-Nobari B, Malek-Mahdavi A, Rashtchizadeh N. Serum YKL-40 levels and disease characteristics in patients with rheumatoid arthritis. Caspian J Intern Med. 2019 Winter;10(1):92-97. PubMed 30858947
13. Basok BI, Kucur M, Kizilgul M, et al. Increased chitotriosidase activities in patients with rheumatoid arthritis: a possible novel marker? J Med Biochem. 2014;33:245-251. doi: 10.2478/jomb-2014-0010
14. Matsumoto T, Tsurumoto T. Serum YKL-40 levels in rheumatoid arthritis: correlations between clinical and laborarory parameters. Clin Exp Rheumatol. 2001 Nov-Dec;19(6):655-660. PubMed 11791636
15. Johansen J, Stoltenberg M, Hansen M, et al. Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity. Rheumatology (Oxford). 1999 Jul;38(7):618-626. PubMed 10461474
16. Volck B, Johansen J, Stoltenberg M, et al. Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology. Osteoarthritis Cartilage. 2001 Apr;9(3):203-214. PubMed 11300743
17. den Broeder AA, Jootsen LAB, Saxne T, et al. Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis. 2002 Apr;61(4):311-318. PubMed 11874832
18. Knudsen LS, Hetland ML, Johansen JS, et al. Changes in Plasma IL-6, Plasma VEGF and Serum YKL-40 During Treatment with Etanercept and Methotrexate or Etanercept alone in Patients with Active Rheumatoid Arthritis despite Methotrexate Therapy. Biomark Insights. 2009 Sep 23;4:91-95. PubMed 20029652
19. Väänänen T, Vuoltteenaho K, Kautiainen H, et al. Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial. PLoS One. 2017 Aug 25;12(8):e0183294. PubMed 28841649
20. Knudsen L, Østergaard M, Baslund B, et al. Plasma IL‐6, plasma VEGF, and serum YKL‐40: relationship with disease activity and radiographic progression in rheumatoid arthritis patients treated with infliximab and methotrexate. Scand J Rheumatol. 2006 Nov-Dec;35(6):489-491. PubMed 17343261
21. Schmidt IM, Hall IE, Kale S, et al. Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. J Am Soc Nephrol. 2013 Feb;24(2):309-319. Epub 2013 Jan 4. PubMed 23291472
22. Puthumana J, Hall IE, Reese PP, et al. YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation. J Am Soc Nephrol. 2017 Feb;28(2):661-670. Epub 2016 Jul 22. PubMed 27451287
23. Wang J, Qi S, Zhu YB, Ding L. Prognostic value of YKL-40 in colorectal carcinoma patients: A meta-analysis. World J Clin Cases. 2022 Mar 6;10(7):2184-2193. PubMed 35321165
24. Cintin C, Johansen JS, Christensen IJ, Price PA, Sørensen S, Nielsen HJ. Serum YKL-40 and colorectal cancer. Br J Cancer. 1999 Mar;79(9-10):1494-1499. PubMed 10188896
25. Cintin C, Johansen JS, Christensen IJ, Price PA, Sørensen S, Nielsen HJ. High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer. 2002 Jul15;95(2)267-274. PubMed 12124825
26. Fuksiewicz M, Kotowicz B, Rutkowski A, Achinger-Kawecka J, Wagrodzki M, Kowalska MM. The Assessment of Clinical Usage and Prognostic Value of YKL-40 Serum Levels in Patients With Rectal Cancer Without Distant Metastasis. Technol Cancer Res Treat. 2018 Jan 1;17:1533033818765209. PubMed 29642772
27. Hermunen K, Soveri LM, Boisen MK, et al. Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer. Acta Oncol. 2020 Dec;59(12):1416-1423. PubMed 32790589
28. Liu X, Zhang Y, Zhu Z, Ha M, Wang Y. Elevated pretreatment serum concentration of YKL-40: an independent prognostic biomarker for poor survival in patients with colorectal cancer. Med Oncol. 2014 Aug;31(8):85. PubMed 24996799
29. Oh IH, Pyo JS, Son BK. Prognostic Impact of YKL-40 Immunohistochemical Expression in Patients with Colorectal Cancer. Curr Oncol. 2021 Aug 19;28(4):3139-3149. PubMed 34436040
30. Peltonen R, Gramkow MH, Dehlendorff C, Osterlund PJ, Johansen JS, Isoniemi H. Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases. PLoS One. 2020 Aug 5;15(8):e0236569. PubMed 32756596
31. Tarpgaard LS, Guren TK, Glimelius B, et al. Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study. PLoS One. 2014 Feb 3;9(2):e87746. PubMed 24498368
32. Yang F, Liu X, Peng Q. The expression and significance of YKL-40, RSK4 and cyclinD1 in colon cancer. Zhongguo. Laonianxue Zhazhi. 2021;41:3938-3943.
33. Prins S, de Kam ML, Teunissen CE, Groeneveld GJ. Inflammatory plasma biomarkers in subjects with preclinical Alzheimer’s disease. Alzheimers Res Ther. 2022 Aug 3;14(1):106. PubMed 35922871
34. Villar-Piqué A, Schmitz M, Hermann P, et al. Plasma YKL-40 in the spectrum of neurodegenerative dementia. J Neuroinflammation. 2019 Jul 12;16(1):145. PubMed 31299989
35. Pase MP, Himali JJ, Puerta R, et al. Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia. Neurology. 2024 Feb 27;102(4):e208075. PubMed 38290090
LOINC® Map
| Order Code | Order Code Name | Order Loinc | Result Code | Result Code Name | UofM | Result LOINC |
|---|---|---|---|---|---|---|
| 140600 | YKL-40 (CHI3L1) Plasma | 48663-9 | 140601 | YKL-40 (CHI3L1) Plasma | ng/mL | Pending |
| Order Code | 140600 | |||||
| Order Code Name | YKL-40 (CHI3L1) Plasma | |||||
| Order Loinc | 48663-9 | |||||
| Result Code | 140601 | |||||
| Result Code Name | YKL-40 (CHI3L1) Plasma | |||||
| UofM | ng/mL | |||||
| Result LOINC | Pending |