Krebs von den Lungen-6(KL-6)
Proven marker ofIntersticial Lung Disease

BACKGROUND
Krebs von den Lungen-6 (KL-6) is a high-molecular mucin-like glycoprotein, encoded by MUC1 gene.
KL-6/MUC1 regulates cell-cell interactions and shows also chemotactic activity. It is distributed mainlyon the cell surface of type II alveolar epithelial cells(AECs). During the inflammatory storm, thedisulfide bonds on the surface of the epithelial cell
membrane may be damaged and KL-6 released
into the pulmonary epithelia lining fluid and bloodcirculation. Increased levels of KL-6 in patientswith IPF are due to higher production of KL-6 byregenerating alveolar type II pneumocytes and by
its increased release following alveolar damage inthe affected lung.
Reference: Ishikawa N, Hattori N, Yokoyama A, Kohno N.
Utility of KL-6/MUC1 in the clinical management ofinterstitial lung diseases. Respir Investig. 2012 Mar;50(1):313. doi: 10.1016/j.resinv.2012.02.001. Epub 2012 Mar 8.
PMID: 22554854.

PRESENCE OF KL-6 IN THE LUNGS
KL-6 is mildly presented in the type II pneumocytes and respiratory bronchiolar epithelial cells andweakly in the basal cells of the bronchiolar epithelium of healthy lungs. No KL-6 expression wasobserved on type I pneumocytes, goblet cells and mucous cells of the bronchial glands. KL-6 is strongly
expressed by the altered and/or regenerating type II pneumocytes in tissue sections obtained from thepatients with IPF.

KL-6 AND INTERSTITIAL LUNG DISEASE (ILD): DIAGNOSIS AND DISEASE ACTIVITY
Interstitial lung disease represents a range ofheterogeneous difussed parenchymal disorders often
characterized by fibrosis of the lungs at advanced
stages, and effecting the alveolar space andpulmonary interstitium. Interstitial Pulmonary
Fibrosis (IPF) is one of IDLs, that is caused by the lossof function of alveoli, bronchioles and pulmonary
interstitium, and its scarring resulting in thedecrease of lung capacity. IPF represents
progressive fibrosing ILD, which could develop also
in the other ILDs. The swiftness of treatment andthe disease activity are vital for good patient prognosis. Increased serum levels of KL-6 were observedin IPF patients in many clinical studies. The comparison of serum KL-6 determined by BioLab Assays
Human KL-6 ELISA kit in healty individuals, patients with sarcoidosis, COPD and IPF reports serum KL-6levels typical for the groups (BioLab Assays in-house data).

Serum_KL_6
100Sensitivity

80604020AUC = 0,969
P < 0,001

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20

40

60

80

100

100-Specificity

Risk serum KL-6 values: over 250 U/ml
(95percentil of healthy individuals)

ROC analysis COPD vs IPF: cut-off 385 U/ml,clinical specificity 90%, clinical sensitivity 92,3 %,AUC 0,969, 95% confidence interval 0,842 to 0,999

Over differentiation among various IDLs, thechallenge is the identification of individuals withextensive lung fibrosis, and progressive fibrosing IDL
respectively. The study from He et al. referredcomparison among non-Interstitial Lung Disease(non-ILD), Interstitial Lung Disease (ILD-all), andseparately non-progressive fibrosing ILD (ILDinactive) against progressive fibrosing ILD (ILDactive).

Reference: He Q, Tang Y, Huang J, Rao Y, Lu Y. The value of KL-6
in the diagnosis and assessment of interstitial lung disease. Am JTransl Res. 2021 Aug 15;13(8):9216-9223. PMID: 34540037;
PMCID: PMC8430136.

KL-6 AND INTERSTITIAL LUNG DISEASE (ILD): MORTALITY IN PATIENTS WITH ACUTE
EXACERBATIONThe changes in blood KL-6 levels within 1 week
hospitalisation were higher in non-survivals.
Patients with remarkable increase in KL-6(≥ 10%) showed significantly worse survival (inhospital mortality: 63.2 vs. 6.1%, mediansurvival: 42 vs. 142 days; P < 0.001) than thosewithout.
Reference: Choi, M.G., Choi, S.M., Lee, J.H. et al. Changes
in blood Krebs von den Lungen-6 predict the mortality ofpatients with acute exacerbation of interstitial lungdisease. Sci Rep 12, article 4916 (2022). PMID: 35318424
https://doi.org/10.1038/s41598-022-08965-9

KL-6 AND SURFACTANT PROTEIN A: A COMPARISON AMONG IPF MARKERS
KL-6 and Surfactant protein A (SP-A) are both claimed to be sensitive markers for interstitial lungdisease (ILD). The study by Ohnishi et. al. compared these two markers finding out that the sensitivity,specificity, and diagnostic accuracy were 93.9%, 96.3%, and 95.7% for KL-6; 81.8%, 86.6%, and 85.2%
for SP-A, respectively. The serum levels of SP-A but not of KL-6 were higher in bacteria pneumonia
group than in healthy individuals, which suggests serum SP-A as the sensitive marker in acuterespiratory distress syndrome (ARDS), while KL-6 is the most efficient marker for IDL.

ILD groups
IPF: Interstitial pulmonary disease; CVD-IP: collagen vasculardisease-associated interstitial pneumonitis
Control groups
Bac. Pneu.: Bacterial pneumonia; Health.: Healthy individuals
Reference: Ohnishi H, Yokoyama A, Kondo K, Hamada H, AbeM, Nishimura K, Hiwada K, Kohno N. Comparative study ofKL-6, surfactant protein-A, surfactant protein-D, andmonocyte chemoattractant protein-1 as serum markers forinterstitial lung diseases. Am J Respir Crit Care Med. 2002 Feb
1;165(3):378-81. doi: 10.1164/ajrccm.165.3.2107134. PMID:11818324.

serum KL-6 is the most sensitive and specific serum marker of interstitial lungdisease (IDL), the release of KL-6 results from alveolar epithelial cell damage
and destruction, a recent meta-analysis observed KL-6 diagnostic sensitivity(0.85, 95% CI, 0.77–0.91) and specificity (0.97, 95% CI, 0.90–0.99) for interstitiallung disease

KL-6

KL-6 levels reflect the severity of interstitial lung disease associated withfibrosing progression of the disease
KL-6 levels are associated with the presence of connective tissue disease in IDLrelated autoimmune diseases: rheumatic arthritis, inflammatory myositis,
Sjoengren's syndrome or systemic lupus erythermatosus (SLE)changes in serum Krebs von den Lungen-6 predict the mortality for patients withacute exacerbation in interstitial lung disease, and for patients with IPF

Human KL-6 ELISA

Cat.No. BA1017
Sandwich ELISA: capture MAb / detection MAbSize: 96 wells
Calibration range: 0.156 – 10 U/ml
Sample type: serum, plasma, BALF
Regulatory status: RUO