Increased serum AXL associated with radiographic knee osteoarthritis severity

Increased serum AXL associated with radiographic knee osteoarthritis severity, finds a new study published in the international journal of rheumatic diseases.

Shao Zhenghai conducted a study (at Shanghai Kaiyuan Orthopedic Hospital, Shanghai, China) to investigate the expression and clinical significance of serum soluble AXL in patients with radiographic knee osteoarthritis (KOA).

KOA is a global issue in the elderly population and early diagnosis is required to begin possible treatment. A broad range of mechanical and biochemical inflammatory mediators (pro-inflammatory cytokines, growth factors, and matrix metalloproteinase) contribute to the pathogenesis of KOA.

The radiography imaging technique is viewed as a gold standard method for diagnosis of KOA, but the current imaging technique is suffering from lack of sensitivity and specificity. Therefore there is an urgency to develop a potential alternative tool for the diagnosis of KOA.

The receptor tyrosine kinase AXL is a 140 kDa protein that belongs to a tyrosine kinase receptor (TAM) subfamily, together with Tyro3 and Mer. The TAM receptors (AXL, Tyro3, and Mer) play a critical role in innate immune homeostasis and vitamin K-dependent ligand growth arrest-specific protein 6 (GAS6) can bind all 3 receptors with the highest affinity for AXL. Transmembrane protein AXL can be cleaved proteolytically at its extracellular membrane domain and subsequently released as soluble AXL, which can be detected in serum or plasma.

The study hypothesized that endogenous AXL concentration may be correlated with the severity of KOA and can predict the development and progression of KOA as seen on radiography of the knee.

183 patients with KOA were selected and divided based on the Kellgren-Lawrence (KL) score into KL 0 subgroups (n = 42), KL I-II subgroups (n = 90), and KL III-IV subgroups (n = 51).

The evaluation of KL grade and double-blind measurement of joint structure were carried out by 2 experienced rheumatologists. When the evaluation of the 2 specialists was different, the joint KL grade and joint structure were evaluated by senior specialists in the Department of Radiology.

Whole blood was collected from fasting participants in the morning. Blood samples were centrifuged (15 000 × g for 10 minutes at 4°C) to separate serum. The processed serum supernatant was then aliquoted into a 1.5 mL Eppendorf tube and stored at −80°C for further analysis.

Healthy volunteers (n = 170) in their hospital were selected with matched age and gender as the control group. AXL level in serum was detected by enzyme-linked immunosorbent assay.

Results:

• There was no significant difference in age and gender between the control group and OA group.

• The mean body mass index (BMI) and erythrocyte sedimentation rate (ESR) were significantly higher in OA patients with respect to healthy controls (both P < .05).

• Analysis of biochemical parameters revealed significantly higher serum CRP, COMP, MMP-13, TGF-β1 and Gas6 levels in the OA group compared to control group (all P < .05).

• The serum AXL level was significantly higher in the OA patients (43.45 [36.61-50.33] ng/mL, coefficient of variation [CV]: 0.213) compared with that in the healthy control (27.38 [24.25-29.82] pg/mL, CV: 0.155) (P < .001)

• Among OA patients, serum AXL levels were significantly higher in subjects with KL I-II grade compared to subjects with KL 0 grade, higher in subjects with KL III-IV compared to subjects with KL I-II grade (both P < .001)

• The optimal cut-off value of serum AXL level was obtained by ROC curve as 33.375 ng/mL, which was used to distinguish healthy controls and all osteoarthritis (including KL 0 to IV)

The author concluded that Serum AXL levels were significantly elevated in KOA patients and have a positive correlation between serum AXL levels with the degree of severity in KOA patients. Measurement of AXL level in the serum can be used as an alternative biomarker to assess the progression of OA in addition to the use of traditional methods for assessing the risk and severity of KOA.

Further reading:

Increased serum AXL is associated with radiographic knee osteoarthritis severity. Shao Zhenghai.

International Journal of Rheumatic Dis. 2022;25:32–37.

DOI: 10.1111/1756-185X.14239