Evaluation of netrin 1 as a new biomarker in the differentiation of psoriatic arthritis from psoriasis

Abstract

This study aimed to evaluate the utility of netrin 1, CRP (C-reactive protein), and ESR (erythrocyte sedimentation rate) biomarkers for distinguishing between psoriatic arthritis (PsA) and psoriasis. This study included 44 patients with PsA and 44 with psoriasis. CASPAR (-Classification criteria for psoriatic arthritis) was used to classify PsA patients, and the PASI (-Psoriasis Area and Severity Index) was used to determine the degree of psoriatic plaques. Serum netrin 1 levels were measured using a commercial, ready-to-use ELISA kit that employs a quantitative immunoassay. Serum netrin 1 and ESR levels were similar between the PsA and psoriasis groups, but the median netrin 1 values were significantly higher in the PsA subtype with axial involvement than in the non-PsA subtype (respectively, 69.9 [64.0–97.6], 58.7 [56.2–64.0], p: 0.002). CRP levels were significantly higher in the PsA group than in the psoriasis group (B: − 0.134, OR [95% CI]: 0.874 [0.783–0.977], p: 0.018). A cut-off value of 12.05 for CRP was found to have a specificity of 27.3% and a sensitivity of 97.7% in distinguishing patients with PsA from those with psoriasis (AUC [95% CI]: 0.699 [0.590–0.809], p: 0.01). Netrin 1 is not a significant biomarker for distinguishing PsA from psoriasis, but it may be a potential biomarker for identifying the PsA subtype with axial involvement. Although CRP is a sensitive biomarker for distinguishing PsA from psoriasis, its specificity is low.

Introductıon

Psoriatic arthritis (PsA), a chronic inflammatory disease, is observed in approximately one-third of patients with psoriasis and affects approximately 0.7% of the general population^1,2. PsA characteristically affects the axial skeleton, peripheral joints, and entheseal areas. It can present with various clinical symptoms, and diagnosis and treatment are often delayed due to the absence of disease-specific clinical signs and symptoms. PsA causes destructive and progressive joint damage, leading to permanent loss of function and decreased quality of life^3,4. Although PsA may develop in one-third of patients with psoriasis, the prevalence of undiagnosed PsA in the setting of psoriasis is approximately 10–15%⁴. Although classification criteria for PsA are used in academic studies, there are currently no accepted criteria or biomarkers for diagnosing PsA⁴. Clinical symptoms in PsA are not specific for the disease, and acute-phase reactants may be normal, particularly in those with axial involvement. Although clinical features such as nail changes, psoriatic plaques on the scalp and intergluteal-perianal area, and the extent of psoriatic lesions may predict the development of PsA in psoriasis, these predictors are not sufficient to distinguish between psoriasis and PsA^5–7.

Numerous biomarker studies have aimed to distinguish PsA from psoriasis. These studies have evaluated cartilage oligomeric metalloproteinase, MMP3 (matrix metalloproteinase-3 ), receptor activator of nuclear kappa-B ligand, osteoprotegerin, dickkopf-1, human leukocyte antigen, anti-cyclic citrullinated peptide, anti-mutated citrullinated vimentin, anti-A disintegrin and thrombospondin motif metalloproteinase-5, anti-cathelicidin LL37, C.X.C motif chemokine ligand 10, and calprotectin molecules as biomarkers. However, the results showed that none of these biomarkers has a specific diagnostic value for PsA⁸. Acute phase reactants, such as CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate), are primarily used as indicators of disease activity. Still, their specificity in distinguishing between PsA and psoriasis is considered low⁹.

Netrin 1, a laminin-like matrix protein, functions as an axonal guidance protein and, when bound to its receptors, adenosine A2B or Unc5b, acts as a chemorepulsant, suppressing mononuclear cell migration^10–12. Netrin 1 promotes angiogenesis via the VEGF receptor and ERK1/2¹³. Netrin 1 production parallels the levels of tumour necrosis factor (TNF)-alpha (α), a molecule involved in inflammatory pathways¹⁴. There is also preclinical evidence that netrin 1 may affect the Th17/Treg balance¹⁵. Cytokines such as TNF-α and interleukin-17 (IL-17), as well as angiogenesis, play essential roles in the development and progression of PsA and psoriasis¹⁶. Due to its close relationship with these pathways, netrin 1 may have potential roles in the pathogenesis of PsA and psoriasis.

Netrin 1, a non-canonical angiogenic factor, can influence vessel formation, suggesting a mechanistic link between the intense vascularisation and endothelial activity in psoriatic plaques¹³. Bioinformatic analyses indicate that signalling components related to the netrin/DCC pathway are included in psoriasis-associated gene networks and may play a role in immune cell-keratinocyte interactions, as well as tissue remodelling¹⁷. However, given the essential role of netrin 1 in neuronal axon guidance, the possibility that this molecule may also contribute to the transport or rerouting of nerve fibres in psoriatic plaques is noteworthy. Increased nerve density and neuropeptide levels (e.g., substance P, CGRP) are known to be present in psoriatic skin lesions. Netrin 1 mediates peripheral pain sensitization by increasing the levels of these neuropeptides in nerve cells¹⁸. These data suggest that netrin 1 may modulate neuroimmune communication between psoriatic plaques and nerve fibres.

Experimental studies suggest that netrin 1 may play contradictory roles in the development of arthritis^19,20. Clinical studies in humans with rheumatic diseases show that serum netrin 1 levels are similar in patients with FMF (Familial Mediterranean fever), primary Sjögren syndrome, and RA (rheumatoid arthritis) compared to healthy controls, and that netrin 1 serum levels do not change with the activity of these diseases. However, although the pathophysiological mechanism of action is not yet precise, netrin 1 levels appear to be associated with diseases such as rheumatoid interstitial lung disease and systemic sclerosis, which are characterised by fibrotic processes^21–25.

Early diagnosis of PsA is a critical therapeutic window, as delayed diagnosis can result in irreversible joint damage due to the rapidly progressive nature of the disease. This study aimed to test the utility of netrin 1 as a biomarker, along with CRP and ESR, in differentiating PsA from psoriasis. Furthermore, the relationship between netrin 1 and the activation of PsA disease, as well as peripheral or axial skeletal involvement, was examined in light of current literature and our patient data.

Materıals and methods

Study design

This study was designed as an analytical cross-sectional case/control study. Exclusion criteria included active/chronic infectious disease, current or past malignancy, pregnancy, and rheumatologic diseases other than PsA. The PsA group consisted of 44 patients with PsA registered in the rheumatology department, and the psoriasis group consisted of 44 patients registered in the dermatology department. PsA patients were classified according to CASPAR (Classification criteria for psoriatic arthritis) criteria²⁶. Forty-four psoriasis patients with similar age, gender, and comorbidity profiles to the PsA group were assigned to the psoriasis group. Patients with histopathological and clinical findings consistent with psoriasis were included in the psoriasis group. The PASI (Psoriasis Area and Severity Index) was used to assess the severity and extent of psoriatic plaques in patients with psoriasis²⁷. DAS28 (modified disease activity score 28)-ESR (0–9.4, range) and BASDAI (-Bath ankylosing spondylitis disease activity index) (0–10, range) scores were used to estimate disease activity in the PsA group^28,29. The automatic DAS28-ESR calculation program from the online database of the website https://trasdonline.org/hesaplayicilar.php?type=das28 was used to calculate the DAS28-ESR. Signed informed consent forms were obtained from all participants included in the study groups before the commencement of the study. The presence of axial involvement in PsA patients was determined by the visualization of sacroiliitis or spondylitis on fat-suppressed T2 or STIR sequences of magnetic resonance (MR) images. Ethical approval was obtained for the study, dated August 16, 2023, and numbered E1-23–3892.

Biochemical analyses for serum netrin 1 measurement

Venous blood samples were separated into vacuum tubes and centrifuged at 1300 × g for 10 min. They were then stored at − 80 °C until measurement. Using a quantitative immunoassay method, a ready-to-use commercial ELISA kit (catalogue no. E-EL-H2328, Elabscience; lot no. GZWTKZ5SWK, Texas, USA) was employed to measure serum netrin 1. For netrin 1 measurement, serum samples and standards added to micro ELISA plate wells were incubated with specific netrin 1 antibodies at 37 °C for approximately 90 min. HRP (Avidin-Horseradish Peroxidase) and biotin-rich human detection antibodies specific for netrin 1 were added to the solution, and the resulting samples were incubated at 37 °C for 30 min. Following incubation, free components were separated by washing, and equal amounts of the resulting substrates were added to each well. Following incubation, a blue color appeared in the wells containing HRP conjugate, biotin-rich detection antibodies, and human netrin 1. The enzyme–substrate reaction was completed by adding stop solution, and the color of the reaction turned yellow in the final step. Optical density levels were used as an indirect indicator to calculate netrin 1 concentrations, and a spectrophotometric microplate reader with a wavelength of 450 nm was employed for this purpose. Serum human netrin 1 levels were calculated using optical density standard curves. The sensitivity of the commercial kit used for netrin 1 ranged from 31.25 to 2000 pg/mL. Netrin 1 levels were measured in a single measurement as recommended in the package insert of the ready-to-use commercial ELISA kit. The inter- and intra-assay variability of the commercial kit used for netrin 1 estimation was < 10% in detecting netrin 1 levels.

Statistical analysis

Shapiro/Wilk-Kolmogorov/Smirnov tests and histogram/probability curves were analytical tests used to assess the normal distribution of continuous variables. Analytical results in descriptive statistics were presented as mean ± SD (standard deviation) for normally distributed variables and as median [interquartile range (IQR), (25–75%)] for non-normally distributed variables. Analytical results for pairwise comparisons were calculated using the Independent Samples T-Test for normal distributions and the Mann–Whitney U test for non-normal distributions. Correlation tests for continuous variables were performed using Spearman or Pearson correlation analyses. Analytical comparisons involving multiple groups were performed using the One-way ANOVA post hoc Tukey test for normal distributions and the independent samples Kruskal–Wallis test for non-normal distributions. The Bonferroni correction was used to calculate P-values for multiple comparisons. Fisher’s or chi-square tests were used to perform analytical tests for categorical variables. The predictive effect of categorical dependent variables on continuous independent variables was assessed using binary logistic regression analysis. ROC analysis was used to determine the diagnostic accuracy of the biomarkers, and the results are presented with 95% confidence intervals for the AUC. The Youden index was used to determine the optimal cut-off values, and the results are presented as diagnostic accuracy criteria (sensitivity/specificity) for the cut-off values. All statistical calculations were performed using SPSS (Statistical Packages for the Social Sciences) version 22.0. For statistical calculations, results with a P value of < 0.05 were considered significant.

Results

Table 1 shows the comparative results of demographic, laboratory, and clinical data for the groups. No significant difference was found between the PsA and psoriasis groups in terms of median netrin 1 values [respectively, 60.8 (56.2–66.6), 59.3 (55.0–66.7), p: 0.488]. Median values for CRP [respectively, 5.9 (2.2–12.4), 2.4 (0.5–5.0), p: 0.001] and ESR [respectively, 15 (6–24.7), 7 (5–15), p: 0.023] were significantly higher in the PsA group compared to the psoriasis group.

Table 1.

Pairwise comparisons of demographic, laboratory and clinical data of the groups.

		PsA	Psoriasis	P value
n (total)		44	44	–
Age, mean ± SD (years)		45 ± 9.6	43 ± 7.9	0.417
Gender female/male, n		24/20	20/24	0.394
Body mass index, mean ± SD		26.9 ± 5.5	27.8 ± 6.9	0.403
Presence of comorbid disease
Chronic obstructive pulmonary disease, n		3	5	0.458
Hypertension, n		2	4	0.398
Diabetes mellitus, n,		2	1	0.557
Coronary artery disease, n		4	3	0.694
Smoking, n (%)		3 (6.8)	5 (11.3)	0.458
Creatinine, median (IQR) [mg/dL]		0.71 (0.61–0.82)	0.70 (0.65–0.81)	0.123
Albumin, median (IQR) [g/dL]		44 (40–47)	45 (42–47)	0.093
Urıc acid, median (IQR) [mg/dL]		5 (4.25–5.5)	5 (3–5.4)	0.366
CRP, median (IQR) [mg/L]		5.9 (2.2–12.4)	2.4 (0.5–5.0)	0.001
ESR, median (IQR) [mm/h]		15 (6–24.7)	7 (5–15)	0.023
Netrin 1, median (IQR) [pg/mL]		60.8 (56.2–66.6)	59.3 (55.0–66.7)	0.488
Sacroiliitis (n:8) or spondylitis (n:2), n total (%)		8 (18.1)	–	–
Dactylitis n (%)		12 (27.2)	–	–
Peripheral arthritis, n (%)		16 (36.3)	–	–
Psoriatic nail changes, n (%)		16 (36.3)	–	–
Hand deformity, n (%)		10 (23)	–	–
Uveitis n (%)		2 (4.5)	–	–
Psoriatic plaque grade, n (%)	None	12 (27.2)	0	–
	Mild	25 (56.8)	19 (43.2)
	Severe	7 (15.9)	25 (56.8)
DAS28-ESR (0–9.4, range), median (IQR)		2.9 (2–3.9)	–	–
BASDAI (0–10, range), median (IQR)		3.2 (1.9–4.2)	–	–

Interquartile range [IQR], Standard deviation [SD], C-reactive protein [-CRP], Disease activity score 28 [-DAS28], Erythrocyte sedimentation rate [-ESR], Bath ankylosing spondylitis disease activity index [-BASDAI]. Significant values are in bold.

The predictive effects of the independent variables CRP, ESR, and netrin 1 on PsA and psoriasis-related variables are shown in Table 2. No significant difference was found between the groups in terms of ESR and netrin 1 (p = 0.349, p = 0.757, respectively). CRP was found to be significantly higher in the PsA group than in the psoriasis group [B (unstandardized Beta): − 0.134, OR (95% CI): 0.874 (0.783–0.977), p: 0.018].

Table 2.

Binary logistic regression analysis results between PsA and psoriasis groups.

	B	Std.error	Wald	OR (CI%95)	P value
Constant	1.371	1.071	1.636		0.201
CRP	− 0.134	0.057	5.633	0.874 (0.783–0.977)	0.018
ESR	− 0.026	0.027	0.878	0.975 (0.924–1.028)	0.349
Netrin 1	− 0.005	0.016	0.096	0.995 (0.964–1.027)	0.757

N: 88, R²: 0.169 (Cox-Snell), R²: 0.225 (Nagelkerke), Model X²(7): 105.692, p: 0.01, Erythrocyte sedimentation rate [-ESR], Unstandardized Beta [B], C-reactive protein [-CRP]. Significant values are in bold.

Figure 1 shows the ROC analysis curve for CRP between PsA and psoriasis groups. A cut-off value of 12.05 for CRP was found to have a specificity of 27.3% and a sensitivity of 97.7% in distinguishing PsA patients from psoriasis [AUC (95%Cl): 0.699 (0.590–0.809), p: 0.01].

Fig. 1.

ROC analysis curve for C-reactive protein.

Table 3 compares serum netrin 1 levels in the PsA and psoriasis groups according to the presence of specific clinical presentations or the type of medication used. Netrin 1 levels were unaffected by the presence of most clinical conditions in PsA and psoriasis or the type of medical treatment used. However, median netrin 1 values were significantly higher in axial spondylitis patients with sacroiliitis or spondylitis compared to patients without axial involvement [respectively, 69.9 (64.0–97.6), 58.7 (56.2–64.0), p: 0.002].

Table 3.

Comparison of serum netrin 1 levels in the psoriatic arthritis and psoriasis groups according to the presence of specific clinical presentations or the type of drugs used in treatment.

Clinic or medicines	Groups	Condition	n	Netrin 1, median (IQR) [pg/mL]	P value
Sacroiliitis or spondylitis	PsA	Available	8	69.9 (64.0–97.6)	0.002
		No	36	58.7 (56.2–64.0)
Peripheral arthritis	PsA	Available	16	61.8 (56.3–67.4)	0.354
		No	28	58.7 (55.8–65.3)
Dactylitis	PsA	Available	12	59.7 (56.3–67.4)	0.866
		No	32	60.8 (56.2–65.8)
Hand deformity	PsA	Available	10	62.1 (56.3–67.4)	0.669
		No	34	60.8 (56.2–65.7)
History of uveitis	PsA	Available	2	69.9 (67.4- )	0.076
		No	42	60.4 (56.2–66.05)
Psoriatic plaque	PsA	None	12	61.9 (56.6–66.4)	0.799
		Mild	25	60.4 (55.9–66.7)
		Severe	7	63.3 (56.2–72.4)
	Psoriasis	None	-		0.177
		Mild	19	56.58 (54.21–64.7)
		Severe	25	60.4 (56.64–68.32)
Psoriatic nail changes	PsA	Available	13	60.5 (57.7–69.9)	0.280
		No	31	61.5 (55.6–65.9)
	Psoriasis	Available	5	62.21 (58.29–65.85)	0.471
		No	39	58.79 (54.93–67.76)
Nonsteroidal anti-inflammatory drug	PsA	Available	10	56.9 (54.5–62.2)	0.032
		No	34	61.3 (57.0–67.4)
	Psoriasis	Available	7	58.3 (55.21–67.49)	0.975
		No	37	59.48 (54.97–66.23)
Methotrexate	PsA	Available	17	57.8 (56.2–64.8)	0.323
		No	27	62.2 (56.7–67.2)
	Psoriasis	Available	27	60.4 (55.41–67.76)	0.412
		No	17	58.3 (54.72–64.85)
Anti-TNF	PsA	Available	10	65.8 (59.7–72.7)	0.134
		No	34	58.7 (56.2–64.8)
	Psoriasis	Available	1	–	0.145
		No	43	59.48 (55.21–67.49)
IL-17 blocker	PsA	Available	7	67.2 (60.4–67.7)	0.038
		No	37	58.7 (55.9–65.8)
	Psoriasis	Available	9	59.48 (54.23–65.68)	0.689
		No	35	59.13 (55.21–67.4)

Psoriatic arthritis [PsA], Anti-Tumor necrosis factor [Anti-TNF], Interleukin-17 [IL-17], *P value after Bonferroni: 0.01667. Significant values are in bold.

Table 4 presents the results of Spearman’s correlation analysis between netrin 1 and several continuous variables. No significant correlation was found between netrin 1 and uric acid, DAS28-ESR, BASDAI, CRP, or ESR.

Table 4.

Correlation analysis between netrin 1 and some continuous variables.

r (p)	Uric acid+	DAS28-ESR*	BASDAI*	CRP+	ESR+
Netrin 1	− 0.085 (0.585)	− 0.076 (0.625)	0.121 (0.433)	0.083 (0.594)	0.121 (0.433)

C-reactive protein [CRP], Correlation coefficient [r], Erythrocyte sedimentation rate [-ESR], Bath ankylosing spondylitis disease activity index [-BASDAI], Disease activity score 28 [-DAS28], *Variables belonging to the PsA group (n:44), ⁺Variables for all groups (n:88).

Dıscussıon

This study tested the utility of serum netrin 1, CRP, and ESR as biomarkers in distinguishing PsA from psoriasis. In addition, this study attempted to determine the relationship between netrin 1 and both PsA disease activities and psoriasis plaque severity.

In our study, netrin 1 levels were similar between the study groups. Netrin 1 has not been previously evaluated in patients with PsA or psoriasis. It is well known that PsA and RA share similar clinical features and radiological erosive joint changes³⁰. Although netrin 1 has not been studied in PsA before, previous studies have suggested that netrin 1 may play conflicting roles in the development of arthritis^19,20. Netrin 1 is an important signalling molecule that regulates immune responses and inflammation, and it has been shown to play a role in chronic inflammation within tissues by affecting macrophage migration, survival, and polarisation³¹. Similarly, macrophage-derived netrin 1 has been reported to accumulate specifically in the synovium, causing local retention of macrophages and contributing to the maintenance of chronic inflammation. Conversely, some experimental models have shown that netrin 1 can reduce tissue damage by promoting anti-inflammatory M2 macrophages³². Studies have shown that treating mice meeting the criteria for chronic joint inflammation with eight weeks of arthritis with monoclonal antibodies that inhibit netrin 1 significantly reduced inflammation and joint erosion (p < 0.001)¹⁹.

Unlike the results of netrin 1 supporting joint inflammation, some studies have reported that netrin 1 UNC5B and UNC5C receptor expressions are higher in RA synovial tissues than in healthy controls, and that treatment with netrin 1 reduces cartilage degeneration by inhibiting the migration of synovial fibroblasts²⁰. Clinical studies have shown that serum netrin 1 levels are similar in healthy individuals and RA patients and that serum netrin 1 levels are unaffected by RA disease activity or joint erosion²⁴. Similarly, this study found that serum netrin 1 levels did not change in association with joint damage and disease activity in PsA. Current literature data and our study results indicate conflicting results regarding the role of netrin 1 in the development of arthritis. Further longitudinal clinical and experimental studies may provide a better understanding of the roles of netrin 1 in diseases associated with joint arthritis and damage.

Although we did not provide any evidence in this study, the question “Can netrin 1 receptor levels be differentially expressed in psoriatic plaques?” seems to be an interesting topic. Literature data indicate that netrin 1 and its central receptors (DCC/neogenin, UNC5 family, etc.) may be regulated differently in psoriatic skin and plaques: Results from transcriptional analyses report different expression profiles in the ROBO-DCC-UNC5 pathways in non-lesional and lesional (plaque) psoriatic skin, indicating that there may be regional differences in netrin 1 receptor levels^33,34. Results from functional studies suggest that netrin 1 may modulate monocyte/neutrophil migration, angiogenesis, and inflammatory responses via the UNC5B receptor³⁵; therefore, increasing or decreasing netrin 1 receptor levels in psoriatic plaques has the potential to influence plaque severity by altering cell infiltration, vasculature, and the degree of inflammation. However, comprehensive immunohistochemical (protein-level) studies directly in human psoriatic plaques are still limited; current evidence is primarily based on transcriptome and serum studies. Therefore, further local (IHC/IF) and quantitative proteomic studies are required to define the receptor distribution at the tissue level definitively.

Serum netrin 1 levels have not been previously studied in patient groups with seronegative spondyloarthropathy, of which PsA is a member. Although the sample size in our study was small, median serum netrin 1 values were found to be higher in patients with axial PsA and sacroiliitis/spondylitis (n: 8) than in those without axial involvement (n: 36). Although the etiopathogenesis of PsA is unclear, cytokines such as TNF-α andIL-17 are known to play essential roles in disease development and progression¹⁶. Experimental studies investigating the effect of netrin 1 on tumour development have shown that TNF-α increases netrin 1 production via the TNFRSF1b receptor¹⁴. This close relationship between netrin 1 and TNF may explain the high serum netrin 1 levels in PsA patients with axial involvement in our study. However, further molecular studies are needed to investigate the pathophysiological roles of netrin 1 in the development of axial spondyloarthritis.

In this study, ESR levels were similar, while CRP levels were significantly higher in the PsA group compared to the psoriasis group. ROC analysis showed that CRP had low specificity but high sensitivity in distinguishing PsA from psoriasis. Another study found the ability of CRP to distinguish between PsA and psoriasis to be similar to our results (AUC [95% CI]: 0.71 [0.64–0.78]). Furthermore, this study reported that CRP performed better in differentiating PsA from psoriasis when used in conjunction with biomarkers such as Mac-2 binding protein and Integrin beta-5 (AUC = 0.85)⁹. Current literature data and our study results suggest that the use of CRP alone in the differential diagnosis of PsA is limited due to its high sensitivity but low specificity.

In our study, the lower serum netrin 1 levels found in NSAID users compared to non-users in PsA patients could be explained by NSAIDs suppressing inflammation, reducing the demand for netrin 1, or by NSAIDs indirectly affecting netrin 1 expression. It has been shown that netrin 1 can normally contribute to the resolution of inflammation by restricting neutrophil migration and promoting the resolution phase of macrophages. Conversely, it has been reported that netrin 1 can also inhibit macrophage migration in some tissues, leading to chronic inflammation³². Therefore, the changes in serum netrin 1 levels affected by NSII in our study may reflect both treatment response and disease activity.

In our study, the higher serum netrin 1 levels in PsA patients using IL-17 blockers is consistent with netrin 1 being an anti-inflammatory and macrophage-directed molecule that plays a role in the “resolution” phase of inflammation³². When IL-17 production is suppressed by treatment, pro-inflammatory Th17 signaling decreases, and consequently, tissue resorption and repair responses may be relatively prioritized, reflecting the increased netrin 1 production. Furthermore, some studies have shown an inverse correlation between netrin 1 and IL-17, and that netrin 1 may reduce inflammatory responses by regulating monocyte/macrophage behavior, cell migration, and NF-κB-mediated cytokine production¹⁵. Therefore, it is possible that IL-17 blockade may create an immunological environment that could lead to elevated netrin 1 levels.

Limitations of this study include its cross-sectional nature, the potential effects of the medications used in treatment on biochemical results, and the inability to perform further statistical analyses due to the small sample size of the PsA subgroups. In addition, the lack of a health control group and the need for additional testing of the reliability of the results obtained from this study constitute other essential limitations of this study. However, this study demonstrated that, although there was no significant difference in the overall patient group, netrin 1 levels were significantly higher in the PsA subgroup with axial involvement, and that netrin 1 may be a more valuable biomarker in distinguishing PsA subphenotypes. Furthermore, this study supports previous studies demonstrating that CRP is a low-specific but highly sensitive biomarker distinguishing PsA from psoriasis.

Conclusion

Although CRP is a sensitive biomarker for differentiating PsA from psoriasis, its specificity is low. Netrin 1 is not a significant biomarker for differentiating PsA from psoriasis, but it may be a potential biomarker for identifying PsA patients with axial involvement. These findings require further support through studies focusing on PsA subphenotypes and utilising larger sample sizes.

Author contributions

Collection of laboratory data—AK, MY, FER, FERD—Evaluation of radiographic—AK, SE, SCG, HEK—Design of the study—AK, SCG—Analysis and interpretation of data and writing of the article—AK—Draft and revision of the article—AK, SE.

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval

This study was approved by the 1st Ethics Committee of Ankara Bilkent City Hospital, dated August 16, 2023, and numbered E1-23-3892. All patients were included in the study after providing informed consent beforehand. All stages of this study were conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice, as well as the country’s legal operating procedures.