BackgroundAlthough many predictors have been proposed to predict rheumatoid arthritis (RA) disease activity, most of these markers are not specific to RA and their levels can be affected by many other factors. The need for ideal markers to predict disease activity in RA continues. The association of netrin-1 with RA disease activity has not been evaluated before.ObjectivesThis study aimed to investigate the plasma levels of the netrin-1 molecule in RA patients and its relationship with RA disease activity.MethodsSixty RA patients and 41 age and sex-matched healthy volunteers were included in this study. An ELISA kit (Elabscience, Texas, USA; catalog number: E-EL-H2328; lot number: GZWTKZ5SWK) analyzed by quantitative sandwich enzyme immunoassay method was used to calculate netrin-1 values. Disease Activity Score-28 (DAS-28) and Clinical Disease Activity Index (CDAI) were calculated to measure disease activity, and Rheumatoid Arthritis Disease Impact (RAID) score was calculated to measure disease-related deterioration in the quality of life.ResultsNetrin-1 serum levels were similar in RA and healthy controls (respectively, 64.4 [35.8-551.4] and 65 [35.8-436.6], p:786). No significant correlation was found between levels of Netrin-1 and DAS-28-CRP, DAS-28-ESR, CDAI, and RAID scores (p>0.05).ConclusionNetrin-1 is not elevated in RA patient serum and its levels are not correlated with RA disease activation scores.References[1] Min HK, Kim KW, Lee SH, Kim HR. Roles of mast cells in rheumatoid arthritis. Korean J Intern Med 2020;35:12-24.[2] da Mota LMH, dos Santos Neto LL, de Carvalho JF.. Autoantibodies and other serological markers in rheumatoid arthritis: predictors of disease activity?. Clin Rheumatol 2009;28:1127-1134.[3] Bradford D, Faull RL, Curtis MA, Cooper HM. Characterization of the netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain. J Comp Neurol 2010;518:3237-3253.[4] Schubert T, Denk A, Mägdefrau U, et al. Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthritis and osteoarthritis. Int J Immunopathol Pharmacol 2009;22:715-722.[5] Maraş Y, Kor A, Oğuz EF, Sari A, Gök K, Akdoğan A. Serum netrin-1 levels in systemic sclerosis patients with capillary abnormalities. Egypt. Rheumatol 2023;45:51-54.Table 1.The relationship between disease activity, treatment status, and serum Netrin-1 levelsNetrin-1 level, pg/mL, median (min-max)DAS28 disease activitypControl (n=41)Remission(n=35)Low(n=11)Moderate(n=11)High(n=3)65 (35.8-436.6)67.7 (38.1 – 551.4)61.2 (35.9 – 305.6)60.8 (36.2 – 133.5)70.6 (52.3 – 187.1)0.809CDAI disease activitypControl(n=41)Remission(n=17)Low(n=24)Moderate(n=14)High(n=5)65 (35.8-436.6)54.1 (38.1 – 501.9)87.5 (35.9 – 551.4)58.4 (41.6 – 133.5)73.1 (41.8– 187.1)0.240Treatment statuspTreatment naïve(n=5)cDMARD alone(n=43)bDMARD with or without cDMARD(n=12)70.6 (46.9 – 501.9)57.3 (35.9 – 551.4)71.3 (41.8 – 273.4)0.735DAS28: Disease Activity Score 28, CDAI: Clinical Disease Activity Index, cDMARD: conventional disease-modifying rheumatic drug, bDMARD: biologic disease-modifying rheumatic drug, tsDMARD: target specific disease- modifying rheumatic drugTable 2.Netrin-1 levels in RA patients according to clinical characteristicsnNetrin-1, pg/mL, median (min-max)pGenderFemale4271.8 (35.9-501.9)0.302Male1855.0 (36.3-551.4)SeropositivitySeropositive4464.4 (35.9-551.4)0.757Seronegative1665.5 (38.1-273.4)RF positivityAbsent3161.1 (35.8-551.4)0.819Present2967.6 (32.3-501.9)Anti-CCP positivity, nAbsent4570.5 (35.8-551.4)0.453Present1557.3 (36.3-305.6)Interstitial lung disease, nAbsent5661.0 (35.9-501.9)0.083Present4284.4 (41.8-551.4)Lung nodulesAbsent5561.2 (35.9-551.4)0.402Present575.3 (41.8-295.4)Hand deformityAbsent2160.1 (35.8-305.6)0.361Present3770.5 (38.5-551.3)RA: rheumatoid disease, RF: rheumatoid factor; anti-CCP: anti-citrullinated peptideAcknowledgements:NIL.Disclosure of InterestsNone Declared.

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