Öz
Amaç
Romatoid artrit (RA) hastalık aktivitesini öngörmek için pek çok belirleyici öne sürülmesine rağmen, bu belirteçlerin çoğu RA’ya özgü değildir ve düzeyleri birçok başka faktörden etkilenebilir. RA’da hastalık aktivitesini tahmin etmek için ideal belirteçlere olan ihtiyaç devam etmektedir. Netrin-1’in RA hastalık aktivitesi ile ilişkisi daha önce değerlendirilmemiştir. Bu çalışmada RA hastalarında netrin-1 molekülünün plazma düzeylerinin ve bunun RA hastalık aktivitesi ile ilişkisinin araştırılması amaçlandı.
Yöntem
Bu çalışmaya 60 RA hastası ile yaş ve cinsiyet uyumlu 41 sağlıklı gönüllü birey dahil edilmiştir. Kantitatif sandviç enzim immünoassay yöntemi ile analiz yapan bir ELISA kiti netrin-1 değerlerinin hesaplanmasında kullanıldı. Hastalık aktivitesini ölçmek için hastalık aktivite skoru-28 (DAS-28) ve Klinik Hastalık Aktivite İndeksi (CDAI), hastalığa bağlı yaşam kalitesinde bozulmayı ölçmek için Romatoid Artrit Hastalığın Etkisi (RAID) skoru hesaplandı.
Bulgular
Netrin-1 serum düzeyleri RA ve sağlıklı kontrollerde benzer bulunmuştur [sırasıyla 64,4 (35,8-551,4), 65 (35,8-436,6), p=0,786]. Netrin-1 ile düzeyleri DAS-28-CRP, DAS-28-ESR, CDAI ve RAID arasında anlamlı bir korelasyon ilişkisi tespit edilmemiştir (p>0,05).
Sonuç
Netrin-1 RA hasta serumlarında yüksek değildir ve düzeylerinin RA hastalık aktive skorları ile korelasyon ilişkisi yoktur.
Anahtar Kelimeler: Romatoid artrit, netrin-1, hastalık aktivitesi, fibrozis
Kaynakça
Min HK, Kim KW, Lee SH, Kim HR. Roles of mast cells in rheumatoid arthritis. Korean J Intern Med. 2020;35:12-24.
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;28:1127-34.
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;518:3237-53.
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;22:715-22.
Broutier L, Creveaux M, Vial J, et al. Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. EMBO Mol Med. 2016;8:96-104.
VanGils JM, Derby MC, Fernandes LR, et al. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol. 2012;13:136-43.
Ramkhelawon B, Hennessy EJ, M´enager M, et al. Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med. 2014;20:377-84.
Mediero A, Ramkhelawon B, Perez-Aso M, Moore KJ, Cronstein BN. Netrin-1 is a critical autocrine/paracrine factor for osteoclast differentiation. J Bone Miner Res. 2014;30:837-54.
Ngoc PL, Komatsuzaki K, Fraser IP, et al. Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci USA. 2005;102:14729-34.
Mediero A, Wilder T, Ramkhelawon B, Moore KJ, Cronstein BN. Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis. FASEB J. 2016;30:3835-44.
Maraş Y, Kor A, Oğuz EF, Sarı A, Gök K, Akdoğan A. Serum netrin-1 levels in systemic sclerosis patients with capillary abnormalities. Egypt Rheumatol. 2023;45:51-4.
Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-81.
Van Riel PL, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34:40-4.
Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005;23:100.
Gossec L, Dougados M, Rincheval N, et al. Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative. Ann Rheum Dis. 2009;68:1680-5.
Chen T, Chen D, Li F, Tan Z. Netrin-1 with stem cells promote angiogenesis in limb ischemic rats. J Surg Res. 2014;192:664-9.
Bai J, Hao J, Zhang X, Cui H, Han J, Cao N. Netrin-1 attenuates the progression of renal dysfunction by blocking endothelial-to-mesenchymal transition in the 5/6 nephrectomy rat model. BMC Nephro. 2016;17:1-9.
Nagoshi H, Taki T, Chinen Y, et al. Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance. Genes Chromosomes Cancer. 2015;54:788-95.
Kefeli U, Kefeli AU, Cabuk D, et al. Netrin-1 in cancer: Potential biomarker and therapeutic target? Tumour Biol. 2017;39:1010428317698388.
Chaturvedi V, Murray MJ. Netrins: evolutionarily conserved regulators of epithelial fusion and closure in development and wound healing. Cells Tissues Organs. 2022;211:193-211.
Bruikman CS, Vreeken D, Hoogeveen RM, et al. Netrin-1 and the grade of atherosclerosis are inversely correlated in humans. Arterioscler Thromb Vasc Biol. 2020;40:462-72.
Mediero A, Ramkhelawon B, Wilder T, et al. Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis. Ann Rheum Dis. 2016;75:1706-13.
Maruyama K, Kawasaki T, Hamaguchi M, et al. Bone-protective Functions of Netrin 1 Protein. J Biol Chem. 2016;291:23854-68.
Atalar E, Gök K, Oğuz EF, Kor A, Maraş Y. Plasma netrin-1 levels in Familial Mediterranean fever: a potential biomarker?. J Exp Clin Med. 2022;39:1202-6.
Ajeganova S, Huizinga TW. Rheumatoid arthritis: Seronegative and seropositive RA: alike but different?. Nat Rev Rheumatol. 2015;11:8-9.
Ruof J, Stucki G. Validity aspects of erythrocyte sedimentation rate and C reactive protein in ankylosing spondylitis: a literature review. J Rheumatol. 1999;26:966-70.
Kerget B, Afşin DE, Kerget F, et al. Association of plasma netrin-1 level with inflammatory balance and comorbidities in patients with acute exacerbation of COPD. Tuberk Toraks. 2021;69:30-8.
Sun H, Zhu Y, Pan H, Chen X, Balestrini JL, Lam TT. Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and bleomycin-Induced Pulmonary Fibrosis. Arthritis Rheumatol. 2016;68:1251-61.
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. J Clin Invest. 2021;131:e136542.
Bhattacharya S, Aggarwal A. M2 macrophages and their role in rheumatic diseases. Rheumatol Int. 2019;39:769-80.
Funes SC, Rios M, Escobar-Vera J, Kalergis AM. Implications of macrophage polarization in autoimmunity. Immunology. 2018;154:186-95.
Ranganathan P, Mohamed R, Jayakumar C, Ramesh G. Guidance cue netrin-1 and the regulation of inflammation in acute and chronic kidney disease. Mediators Inflamm. 2014;2014:525891.
Zhang Y, ChenP, Di G, Qi X, Zhou Q, Gao H. Netrin-1 promotes diabetic corneal wound healing through molecular mechanisms mediated via the adenosine 2B receptor. Sci Rep. 2018;8:1-12.
Ranganathan PV, Jayakumar C, Ramesh G. Netrin-1-treated macrophages protect the kidney against ischemia-reperfusion injury and suppress inflammation by inducing M2 polarization. Am J Physiol Renal Physiol. 2013;304:948-57.
