Login Register Cart 0
Mini-Review Article

An Update on the Emerging Role of Wnt/β-catenin, SYK, PI3K/AKT, and GM-CSF Signaling Pathways in Rheumatoid Arthritis

Author(s): Pradyuman Prajapati and Gaurav Doshi*

Volume 24, Issue 17, 2023

Published on: 11 December, 2023

Page: [1298 - 1316] Pages: 19

DOI: 10.2174/0113894501276093231206064243

Price: $65

Open Access Journals Promotions 2
Abstract

Rheumatoid arthritis is an untreatable autoimmune disorder. The disease is accompanied by joint impairment and anomalies, which negatively affect the patient’s quality of life and contribute to a decline in manpower. To diagnose and treat rheumatoid arthritis, it is crucial to understand the abnormal signaling pathways that contribute to the disease. This understanding will help develop new rheumatoid arthritis-related intervention targets. Over the last few decades, researchers have given more attention to rheumatoid arthritis. The current review seeks to provide a detailed summary of rheumatoid arthritis, highlighting the basic description of the disease, past occurrences, the study of epidemiology, risk elements, and the process of disease progression, as well as the key scientific development of the disease condition and multiple signaling pathways and enumerating the most current advancements in discovering new rheumatoid arthritis signaling pathways and rheumatoid arthritis inhibitors. This review emphasizes the anti-rheumatoid effects of these inhibitors [for the Wnt/β-catenin, Phosphoinositide 3-Kinases (PI3K/AKT), Spleen Tyrosine Kinase (SYK), and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) signaling pathways], illustrating their mechanism of action through a literature search, current therapies, and novel drugs under pre-clinical and clinical trials.

Keywords: Rheumatoid arthritis, Wnt/β-catenin, phosphoinositide 3- kinases (PI3K/AKT), spleen tyrosine kinase (SYK), granulocyte- macrophage colony stimulating factor (GM-CSF), autoimmune disorder, novel targets, inflammation.

« Previous Next »
Graphical Abstract

[1]
Lin YJ, Anzaghe M, Schülke S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells 2020; 9(4): 880.
[http://dx.doi.org/10.3390/cells9040880] [PMID: 32260219]
[2]
Littlejohn EA, Monrad SU. Early diagnosis and treatment of rheumatoid arthritis. Primary Care - Clinics in Office Practice 2018; 45(2): 237-55.
[http://dx.doi.org/10.1016/j.pop.2018.02.010]
[3]
Silman AJ, Pearson JE. epidemiology 2020; 265-72.
[4]
van der Woude D, van der Helm-van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2018; 32(2): 174-87.
[http://dx.doi.org/10.1016/j.berh.2018.10.005] [PMID: 30527425]
[5]
Espinoza G, Maldonado G, Narvaez J, Guerrero R, Citera G, Rios C. Beyond rheumatoid arthritis evaluation: What are we missing? Open Access Rheumatol 2021; 13: 45-55.
[http://dx.doi.org/10.2147/OARRR.S298393] [PMID: 33790666]
[6]
Conforti A, Di Cola I, Pavlych V, et al. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmun Rev 2021; 20(2): 102735.
[http://dx.doi.org/10.1016/j.autrev.2020.102735] [PMID: 33346115]
[7]
Kötter I, Stübiger N, Deuter C. [Ocular involvement in rheumatoid arthritis, connective tissue diseases and vasculitis]. Z Rheumatol 2017; 76(8): 673-81. [Ocular involvement in rheumatoid arthritis, connective tissue diseases and vasculitis].
[PMID: 28861674]
[8]
Feist E, Pleyer U. Diseases of the outer eye in rheumatoid arthritis. Z Rheumatol 2010; 69(5): 403-10.
[http://dx.doi.org/10.1007/s00393-009-0577-5] [PMID: 20559644]
[9]
Vignesh APP, Srinivasan R. Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies. Clin Ophthalmol 2015; 9: 393-7.
[PMID: 25750517]
[10]
Hurd ER. Extraarticular manifestations of rheumatoid arthritis. Semin Arthritis Rheum 1979; 8(3): 151-76.
[http://dx.doi.org/10.1016/S0049-0172(79)80005-0] [PMID: 370982]
[11]
Nurmohamed MT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol 2015; 11(12): 693-704.
[http://dx.doi.org/10.1038/nrrheum.2015.112] [PMID: 26282082]
[12]
Romano S, Salustri E, Ruscitti P, Carubbi F, Penco M, Giacomelli R. Cardiovascular and metabolic comorbidities in rheumatoid arthritis. Curr Rheumatol Rep 2018; 20(12): 81.
[http://dx.doi.org/10.1007/s11926-018-0790-9] [PMID: 30397830]
[13]
Ruscitti P, Cipriani P, Liakouli V, et al. Subclinical and clinical atherosclerosis in rheumatoid arthritis: Results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study. Arthritis Res Ther 2019; 21(1): 204.
[http://dx.doi.org/10.1186/s13075-019-1975-y] [PMID: 31481105]
[14]
Tang MW, Garcia S, Gerlag DM, Tak PP, Reedquist KA. Insight into the endocrine system and the immune system: A review of the inflammatory role of prolactin in rheumatoid arthritis and psoriatic arthritis. Front Immunol 2017; 8: 720.
[http://dx.doi.org/10.3389/fimmu.2017.00720] [PMID: 28690611]
[15]
Sparks JA. Rheumatoid arthritis. Ann Intern Med 2019; 170(1): ITC1-ITC16.
[http://dx.doi.org/10.7326/AITC201901010] [PMID: 30596879]
[16]
Pope JE. Management of fatigue in rheumatoid arthritis. RMD Open 2020; 6(1): e001084.
[http://dx.doi.org/10.1136/rmdopen-2019-001084] [PMID: 32385141]
[17]
Cush JJ. Rheumatoid arthritis. Med Clin North Am 2021; 105(2): 355-65.
[http://dx.doi.org/10.1016/j.mcna.2020.10.006] [PMID: 33589108]
[18]
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365(23): 2205-19.
[http://dx.doi.org/10.1056/NEJMra1004965] [PMID: 22150039]
[19]
Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun 2020; 110: 102400.
[http://dx.doi.org/10.1016/j.jaut.2019.102400] [PMID: 31980337]
[20]
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016; 388(10055): 2023-38.
[http://dx.doi.org/10.1016/S0140-6736(16)30173-8] [PMID: 27156434]
[21]
Lu MC, Lai NS, Yu HC, Huang HB, Hsieh SC, Yu CL. Anti–citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor α production. Arthritis Rheum 2010; 62(5): 1213-23.
[http://dx.doi.org/10.1002/art.27386] [PMID: 20213805]
[22]
van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development 2009; 136(19): 3205-14.
[http://dx.doi.org/10.1242/dev.033910] [PMID: 19736321]
[23]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012; 149(6): 1192-205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[24]
Jafari M, Ghadami E, Dadkhah T, Akhavan-Niaki H. PI3k/AKT signaling pathway: Erythropoiesis and beyond. J Cell Physiol 2019; 234(3): 2373-85.
[http://dx.doi.org/10.1002/jcp.27262] [PMID: 30192008]
[25]
Mócsai A, Ruland J, Tybulewicz VLJ. The SYK tyrosine kinase: A crucial player in diverse biological functions. Nat Rev Immunol 2010; 10(6): 387-402.
[http://dx.doi.org/10.1038/nri2765] [PMID: 20467426]
[26]
Shiomi A, Usui T. Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators Inflamm 2015; 2015: 1-13.
[http://dx.doi.org/10.1155/2015/568543] [PMID: 25838639]
[27]
Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982; 31(1): 99-109.
[http://dx.doi.org/10.1016/0092-8674(82)90409-3] [PMID: 6297757]
[28]
Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 2012; 13(12): 767-79.
[http://dx.doi.org/10.1038/nrm3470] [PMID: 23151663]
[29]
Clevers H. Wnt/beta-catenin signaling in development and disease. Cell 2006; 127(3): 469-80.
[http://dx.doi.org/10.1016/j.cell.2006.10.018] [PMID: 17081971]
[30]
Perugorria MJ, Olaizola P, Labiano I, et al. Wnt–β-catenin signalling in liver development, health and disease. Nat Rev Gastroenterol Hepatol 2019; 16(2): 121-36.
[http://dx.doi.org/10.1038/s41575-018-0075-9] [PMID: 30451972]
[31]
Skronska-Wasek W, Mutze K, Baarsma HA, et al. Reduced frizzled receptor 4 expression prevents WNT/β-Catenin–driven alveolar lung repair in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2017; 196(2): 172-85.
[http://dx.doi.org/10.1164/rccm.201605-0904OC] [PMID: 28245136]
[32]
Nusse R, Clevers H. Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities. Cell 2017; 169(6): 985-99.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[33]
Zhu M, Ding Q, Lin Z, et al. New targets and strategies for rheumatoid arthritis: From signal transduction to epigenetic aspect. Biomolecules 2023; 13(5): 766.
[http://dx.doi.org/10.3390/biom13050766] [PMID: 37238636]
[34]
Lie DC, Colamarino SA, Song HJ, et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature 2005; 437(7063): 1370-5.
[http://dx.doi.org/10.1038/nature04108] [PMID: 16251967]
[35]
Miao C, Yang Y, He X, et al. Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different roles in synovial inflammation and bone remodeling. Cell Signal 2013; 25(10): 2069-78.
[http://dx.doi.org/10.1016/j.cellsig.2013.04.002] [PMID: 23602936]
[36]
Rabelo FS, da Mota LMH, Lima RAC, et al. The Wnt signaling pathway and rheumatoid arthritis. Autoimmun Rev 2010; 9(4): 207-10.
[http://dx.doi.org/10.1016/j.autrev.2009.08.003] [PMID: 19683077]
[37]
Sun J, Yan P, Chen Y, et al. MicroRNA-26b inhibits cell proliferation and cytokine secretion in human RASF cells via the Wnt/GSK-3β/β-catenin pathway. Diagn Pathol 2015; 10(1): 72.
[http://dx.doi.org/10.1186/s13000-015-0309-x]
[38]
Gao C, Chen YG. Dishevelled: The hub of Wnt signaling. Cell Signal 2010; 22(5): 717-27.
[http://dx.doi.org/10.1016/j.cellsig.2009.11.021] [PMID: 20006983]
[39]
Sen M. Wnt signalling in rheumatoid arthritis. Rheumatology 2005; 44(6): 708-13.
[http://dx.doi.org/10.1093/rheumatology/keh553] [PMID: 15705634]
[40]
Tsukasaki M, Takayanagi H. Osteoimmunology: Evolving concepts in bone–immune interactions in health and disease. Nat Rev Immunol 2019; 19(10): 626-42.
[http://dx.doi.org/10.1038/s41577-019-0178-8] [PMID: 31186549]
[41]
Świerkot J, Gruszecka K, Matuszewska A, Wiland P. Assessment of the effect of methotrexate therapy on bone metabolism in patients with rheumatoid arthritis. Arch Immunol Ther Exp 2015; 63(5): 397-404.
[http://dx.doi.org/10.1007/s00005-015-0338-x] [PMID: 25837853]
[42]
Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13(2): 156-63.
[http://dx.doi.org/10.1038/nm1538] [PMID: 17237793]
[43]
Wehmeyer C, Frank S, Beckmann D, et al. Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction. Sci Transl Med 2016; 8(330): 330ra35.
[http://dx.doi.org/10.1126/scitranslmed.aac4351] [PMID: 27089204]
[44]
Chen XX, Baum W, Dwyer D, et al. Sclerostin inhibition reverses systemic, periarticular and local bone loss in arthritis. Ann Rheum Dis 2013; 72(10): 1732-6.
[http://dx.doi.org/10.1136/annrheumdis-2013-203345] [PMID: 23666928]
[45]
Marenzana M, Vugler A, Moore A, Robinson M. Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study. Arthritis Res Ther 2013; 15(5): R125.
[http://dx.doi.org/10.1186/ar4305] [PMID: 24432364]
[46]
Rauner M, Stein N, Winzer M, et al. WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production. J Bone Miner Res 2012; 27(3): 575-85.
[http://dx.doi.org/10.1002/jbmr.1488] [PMID: 22162112]
[47]
Sato A, Kayama H, Shojima K, et al. The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis. Sci Rep 2015; 5(1): 10536.
[http://dx.doi.org/10.1038/srep10536] [PMID: 26030277]
[48]
Miao P, Zhou XW, Wang P, et al. Regulatory effect of anti-gp130 functional mAb on IL-6 mediated RANKL and Wnt5a expression through JAK-STAT3 signaling pathway in FLS. Oncotarget 2018; 9(29): 20366-76.
[http://dx.doi.org/10.18632/oncotarget.23917] [PMID: 29755657]
[49]
Kwon YJ, Lee SW, Park YB, Lee SK, Park MC. Secreted frizzled-related protein 5 suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through down-regulation of c-Jun N-terminal kinase. Rheumatology 2014; 53(9): 1704-11.
[http://dx.doi.org/10.1093/rheumatology/keu167] [PMID: 24764263]
[50]
Pukrop T, Klemm F, Hagemann T, et al. Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci 2006; 103(14): 5454-9.
[http://dx.doi.org/10.1073/pnas.0509703103] [PMID: 16569699]
[51]
Enomoto M, Hayakawa S, Itsukushima S, et al. Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene 2009; 28(36): 3197-208.
[http://dx.doi.org/10.1038/onc.2009.175] [PMID: 19561643]
[52]
Delgado-Calle J, Sato AY, Bellido T. Role and mechanism of action of sclerostin in bone. Bone 2017; 96: 29-37.
[http://dx.doi.org/10.1016/j.bone.2016.10.007] [PMID: 27742498]
[53]
Xie W, Zhou L, Li S, Hui T, Chen D. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci 2016; 1364(1): 25-31.
[http://dx.doi.org/10.1111/nyas.12968] [PMID: 26629686]
[54]
Heiland GR, Zwerina K, Baum W, et al. Neutralisation of Dkk-1 protects from systemic bone loss during inflammation and reduces sclerostin expression. Ann Rheum Dis 2010; 69(12): 2152-9.
[http://dx.doi.org/10.1136/ard.2010.132852] [PMID: 20858621]
[55]
Wang SY, Liu YY, Ye H, et al. Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis. J Rheumatol 2011; 38(5): 821-7.
[http://dx.doi.org/10.3899/jrheum.100089] [PMID: 21362762]
[56]
Singh A, Gupta MK, Mishra SP. Study of correlation of level of expression of Wnt signaling pathway inhibitors sclerostin and dickkopf-1 with disease activity and severity in rheumatoid arthritis patients. Drug Discov Ther 2019; 13(1): 22-7.
[http://dx.doi.org/10.5582/ddt.2019.01011] [PMID: 30880318]
[57]
Seror R, Boudaoud S, Pavy S, et al. Increased dickkopf-1 in recent-onset rheumatoid arthritis is a new biomarker of structural severity. Sci Rep 2016; 6(1): 18421.
[http://dx.doi.org/10.1038/srep18421] [PMID: 26785768]
[58]
Cici D, Corrado A, Rotondo C, Cantatore FP. Wnt signaling and biological therapy in rheumatoid arthritis and spondyloarthritis. Int J Mol Sci 2019; 20(22): 5552.
[http://dx.doi.org/10.3390/ijms20225552] [PMID: 31703281]
[59]
Guo J, Wang F, Hu Y, et al. Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases. Cell Rep Med 2023; 4(1): 100881.
[http://dx.doi.org/10.1016/j.xcrm.2022.100881] [PMID: 36603578]
[60]
Aksentijevich I. The sickening consequences of too much SYK signaling. Nat Genet 2021; 53(4): 432-4.
[http://dx.doi.org/10.1038/s41588-021-00837-8] [PMID: 33782606]
[61]
Cha HS, Boyle DL, Inoue T, et al. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther 2006; 317(2): 571-8.
[http://dx.doi.org/10.1124/jpet.105.097436] [PMID: 16452391]
[62]
Iwata S, Nakayamada S, Fukuyo S, et al. Activation of Syk in peripheral blood B cells in patients with rheumatoid arthritis: a potential target for abatacept therapy. Arthritis Rheumatol 2015; 67(1): 63-73.
[http://dx.doi.org/10.1002/art.38895] [PMID: 25303149]
[63]
Ghoshdastidar K, Patel H, Bhayani H, et al. ZYBT1, a potent, irreversible Bruton’s Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer. Pharmacol Res Perspect 2020; 8(4): e00565.
[http://dx.doi.org/10.1002/prp2.565] [PMID: 32790160]
[64]
Kunwar S, Devkota AR, Ghimire DKC. Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials. Rheumatol Int 2016; 36(8): 1077-87.
[http://dx.doi.org/10.1007/s00296-016-3482-7] [PMID: 27113955]
[65]
R. VV. Efficacy and safety of MK-8457, a novel SYK inhibitor for the treatment of rheumatoid arthritis in two randomized, controlled, phase 2 studies. Arthritis Rheumatol 2014; 66: S673-4.
[66]
Currie KS, Kropf JE, Lee T, et al. Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase. J Med Chem 2014; 57(9): 3856-73.
[http://dx.doi.org/10.1021/jm500228a] [PMID: 24779514]
[67]
Coffey G, DeGuzman F, Lee G, et al. PRT062070: A Dual Syk/JAK inhibitor with potent immune regulatory capacity in rodent models of inflammation and cancer. Blood 2012; 120(21): 2764-4.
[http://dx.doi.org/10.1182/blood.V120.21.2764.2764]
[68]
Coffey G, DeGuzman F, Inagaki M, et al. Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J Pharmacol Exp Ther 2012; 340(2): 350-9.
[http://dx.doi.org/10.1124/jpet.111.188441] [PMID: 22040680]
[69]
Norman P. Spleen tyrosine kinase inhibitors: A review of the patent literature 2010 – 2013. Expert Opin Ther Pat 2014; 24(5): 573-95.
[http://dx.doi.org/10.1517/13543776.2014.890184] [PMID: 24555683]
[70]
Kjelgaard-Petersen CF, Platt A, Braddock M, et al. Translational biomarkers and ex-vivo models of joint tissues as a tool for drug development in rheumatoid arthritis. Arthritis Rheumatol 2018; 70(9): 1419-28.
[http://dx.doi.org/10.1002/art.40527] [PMID: 29669391]
[71]
Genovese MC, van der Heijde DM, Keystone EC, et al. A phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 2 dosing regimens of fostamatinib in patients with rheumatoid arthritis with an inadequate response to a tumor necrosis factor-α antagonist. J Rheumatol 2014; 41(11): 2120-8.
[http://dx.doi.org/10.3899/jrheum.140238] [PMID: 25225285]
[72]
Taylor PC, Genovese MC, Greenwood M, et al. OSKIRA-4: A phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy. Ann Rheum Dis 2015; 74(12): 2123-9.
[http://dx.doi.org/10.1136/annrheumdis-2014-205361] [PMID: 25074688]
[73]
Tanaka Y, Millson D, Iwata S, Nakayamada S. Safety and efficacy of fostamatinib in rheumatoid arthritis patients with an inadequate response to methotrexate in phase II OSKIRA-ASIA-1 and OSKIRA-ASIA-1X study. Rheumatology (Oxford) 2021; 60(6): 2884-95.
[http://dx.doi.org/10.1093/rheumatology/keaa732] [PMID: 33254235]
[74]
Genovese MC, Kavanaugh A, Weinblatt ME, et al. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: A three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum 2011; 63(2): 337-45.
[http://dx.doi.org/10.1002/art.30114] [PMID: 21279990]
[75]
Markman B, Dienstmann R, Tabernero J. Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs. Oncotarget 2010; 1(7): 530-43.
[http://dx.doi.org/10.18632/oncotarget.188] [PMID: 21317449]
[76]
Sun K, Luo J, Guo J, Yao X, Jing X, Guo F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review. Osteoarthritis Cartilage 2020; 28(4): 400-9.
[77]
Abeyrathna P, Su Y. The critical role of Akt in cardiovascular function. Vascul Pharmacol 2015; 74: 38-48.
[http://dx.doi.org/10.1016/j.vph.2015.05.008] [PMID: 26025205]
[78]
Chen CY, Chen J, He L, Stiles BL. PTEN: Tumor Suppressor and Metabolic Regulator. Front Endocrinol 2018; 9: 338.
[79]
Ersahin T, Tuncbag N, Cetin-Atalay R. The PI3K/AKT/mTOR interactive pathway. Mol Biosyst 2015; 11(7): 1946-54.
[http://dx.doi.org/10.1039/C5MB00101C] [PMID: 25924008]
[80]
Sathe A, Nawroth R. Targeting the PI3K/AKT/mTOR pathway in bladder cancer. In: Methods in molecular biology. Methods Mol Biol 2018; 335-50.
[81]
Tsai CH, Liu SC, Wang YH, et al. Osteopontin inhibition of miR-129-3p enhances IL-17 expression and monocyte migration in rheumatoid arthritis. Biochim Biophys Acta, Gen Subj 2017; 1861(2): 15-22.
[http://dx.doi.org/10.1016/j.bbagen.2016.11.015] [PMID: 27851983]
[82]
Shoda H, Nagafuchi Y, Tsuchida Y, et al. Increased serum concentrations of IL-1 beta, IL-21 and Th17 cells in overweight patients with rheumatoid arthritis. Arthritis Res Ther 2017; 19(1): 111.
[http://dx.doi.org/10.1186/s13075-017-1308-y] [PMID: 28569167]
[83]
Kwok SK, Cho ML, Park MK, et al. Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis. Arthritis Rheum 2012; 64(3): 740-51.
[http://dx.doi.org/10.1002/art.33390] [PMID: 21968544]
[84]
Mitra A, Raychaudhuri SK, Raychaudhuri SP. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 2012; 60(1): 38-42.
[http://dx.doi.org/10.1016/j.cyto.2012.06.316] [PMID: 22840496]
[85]
Dinesh P, Rasool M. Berberine inhibits IL-21/IL-21R mediated inflammatory proliferation of fibroblast-like synoviocytes through the attenuation of PI3K/Akt signaling pathway and ameliorates IL-21 mediated osteoclastogenesis. Cytokine 2018; 106: 54-66.
[http://dx.doi.org/10.1016/j.cyto.2018.03.005] [PMID: 29549724]
[86]
Shen P, Deng X, Chen Z, et al. SIRT1: A potential therapeutic target in autoimmune diseases. Front Immunol 2021; 12(November): 779177.
[http://dx.doi.org/10.3389/fimmu.2021.779177] [PMID: 34887866]
[87]
Zou L, Zhang G, Liu L, Chen C, Cao X, Cai J. Relationship between PI3K pathway and angiogenesis in CIA rat synovium. Am J Transl Res 2016; 8(7): 3141-7.
[PMID: 27508035]
[88]
Ba X, Huang Y, Shen P, et al. WTD attenuating rheumatoid arthritis via suppressing angiogenesis and modulating the PI3K/AKT/mTOR/HIF-1α pathway. Front Pharmacol 2021; 12: 696802.
[http://dx.doi.org/10.3389/fphar.2021.696802] [PMID: 34646130]
[89]
Li GQ, Zhang Y, Liu D, et al. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial–mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol Cell Biochem 2013; 372(1-2): 221-31.
[http://dx.doi.org/10.1007/s11010-012-1463-z] [PMID: 23001847]
[90]
Du H, Zhang X, Zeng Y, et al. A novel phytochemical, DIM, inhibits proliferation, migration, invasion and TNF-α Induced inflammatory cytokine production of synovial fibroblasts from rheumatoid arthritis patients by targeting MAPK and AKT/mTOR signal pathway. Front Immunol 2019; 10(July): 1620.
[http://dx.doi.org/10.3389/fimmu.2019.01620] [PMID: 31396207]
[91]
Suto T, Karonitsch T. The immunobiology of mTOR in autoimmunity. J Autoimmun 2020; 110(November): 102373.
[http://dx.doi.org/10.1016/j.jaut.2019.102373] [PMID: 31831256]
[92]
Kim J, Jung KH, Yoo J, et al. PBT-6, a novel PI3KC2Γ inhibitor in rheumatoid arthritis. Biomol Ther 2020; 28(2): 172-83.
[http://dx.doi.org/10.4062/biomolther.2019.153] [PMID: 31739383]
[93]
Toyama S, Tamura N, Haruta K, et al. Inhibitory effects of ZSTK474, a novel phosphoinositide 3-kinase inhibitor, on osteoclasts and collagen-induced arthritis in mice. Arthritis Res Ther 2010; 12(3): R92.
[http://dx.doi.org/10.1186/ar3019] [PMID: 20482767]
[94]
Patel L, Chandrasekhar J, Evarts J, et al. Discovery of orally efficacious phosphoinositide 3-Kinase δ inhibitors with improved metabolic stability. J Med Chem 2016; 59(19): 9228-42.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01169] [PMID: 27660855]
[95]
Kamson DO, Khela HS, Laterra J. Investigational new drugs against glioblastoma. In: Paulmurugan R, Massoud TF, Eds. Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies. Academic Press 2021; pp. 31-77.
[96]
Chen J, Lin X, He J, et al. Artemisitene suppresses rheumatoid arthritis progression via modulating METTL3-mediated N6-methyladenosine modification of ICAM2 mRNA in fibroblast-like synoviocytes. Clin Transl Med 2022; 12(12): e1148.
[http://dx.doi.org/10.1002/ctm2.1148] [PMID: 36536495]
[97]
Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 2007; 178(1): 39-48.
[http://dx.doi.org/10.4049/jimmunol.178.1.39] [PMID: 17182538]
[98]
Hansen G, Hercus TR, McClure BJ, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 2008; 134(3): 496-507.
[http://dx.doi.org/10.1016/j.cell.2008.05.053] [PMID: 18692472]
[99]
van Nieuwenhuijze A, Koenders M, Roeleveld D, Sleeman MA, van den Berg W, Wicks IP. GM-CSF as a therapeutic target in inflammatory diseases. Mol Immunol 2013; 56(4): 675-82.
[http://dx.doi.org/10.1016/j.molimm.2013.05.002] [PMID: 23933508]
[100]
Xu D, Zhao M, Song Y, Song J, Huang Y, Wang J. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: Review on the effects of GM-CSF in maintaining homeostasis of the immune system. Hepatol Int 2015; 9(1): 28-34.
[http://dx.doi.org/10.1007/s12072-014-9588-7] [PMID: 25788376]
[101]
Wicks IP, Roberts AW. Targeting GM-CSF in inflammatory diseases. Nat Rev Rheumatol 2016; 12(1): 37-48.
[http://dx.doi.org/10.1038/nrrheum.2015.161] [PMID: 26633290]
[102]
Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 2018; 233(9): 6425-40.
[http://dx.doi.org/10.1002/jcp.26429] [PMID: 29319160]
[103]
Li BZ, Ye QL, Xu WD, Li JH, Ye DQ, Xu Y. GM-CSF alters dendritic cells in autoimmune diseases. Autoimmunity 2013; 46(7): 409-18.
[http://dx.doi.org/10.3109/08916934.2013.803533] [PMID: 23786272]
[104]
Shiomi A, Usui T, Mimori T. GM-CSF as a therapeutic target in autoimmune diseases. Inflamm Regen 2016; 36(1): 8.
[http://dx.doi.org/10.1186/s41232-016-0014-5] [PMID: 29259681]
[105]
Bhattacharya P, Budnick I, Singh M, et al. Dual Role of GM-CSF as a pro-inflammatory and a regulatory cytokine: Implications for immune therapy. J Interferon Cytokine Res 2015; 35(8): 585-99.
[http://dx.doi.org/10.1089/jir.2014.0149] [PMID: 25803788]
[106]
Farahat MN, Yanni G, Poston R, Panayi GS. Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 1993; 52(12): 870-5.
[http://dx.doi.org/10.1136/ard.52.12.870] [PMID: 8311538]
[107]
Bell AL, Magill MK, McKane WR, Kirk F, Irvine AE. Measurement of colony-stimulating factors in synovial fluid: Potential clinical value. Rheumatol Int 1995; 14(5): 177-82.
[http://dx.doi.org/10.1007/BF00262295] [PMID: 7536953]
[108]
Field M, Clinton L. Expression of GM-CSF receptor In rheumatold arthritis. Lancet 1993; 342(8881): 1244.
[http://dx.doi.org/10.1016/0140-6736(93)92229-M] [PMID: 7901565]
[109]
Berenbaum F, Rajzbaum G, Amor B, Toubert A. Evidence for GM-CSF receptor expression in synovial tissue. An analysis by semi-quantitative polymerase chain reaction on rheumatoid arthritis and osteoarthritis synovial biopsies. Eur Cytokine Netw 1994; 5(1): 43-6.
[PMID: 8049356]
[110]
Mulherin D, Fitzgerald O, Bresnihan B. Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 1996; 39(1): 115-24.
[http://dx.doi.org/10.1002/art.1780390116] [PMID: 8546720]
[111]
Haringman JJ, Gerlag DM, Zwinderman AH, et al. Synovial tissue macrophages: A sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 2005; 64(6): 834-8.
[http://dx.doi.org/10.1136/ard.2004.029751] [PMID: 15576415]
[112]
Wijbrandts CA, Vergunst CE, Haringman JJ, Gerlag DM, Smeets TJM, Tak PP. Absence of changes in the number of synovial sublining macrophages after ineffective treatment for rheumatoid arthritis: Implications for use of synovial sublining macrophages as a biomarker. Arthritis Rheum 2007; 56(11): 3869-71.
[http://dx.doi.org/10.1002/art.22964] [PMID: 17968928]
[113]
Codarri L, Gyülvészi G, Tosevski V, et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011; 12(6): 560-7.
[http://dx.doi.org/10.1038/ni.2027] [PMID: 21516112]
[114]
El-Behi M, Ciric B, Dai H, et al. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011; 12(6): 568-75.
[http://dx.doi.org/10.1038/ni.2031] [PMID: 21516111]
[115]
Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res 2001; 3(5): 293-8.
[http://dx.doi.org/10.1186/ar318] [PMID: 11549370]
[116]
Plater-Zyberk C, Joosten L A B, Helsen MMA, Hepp J, Baeuerle PA, van den Berg WB. GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice. Ann Rheum Dis 2006; 66(4): 452-7.
[http://dx.doi.org/10.1136/ard.2006.057182] [PMID: 17020908]
[117]
Campbell IK, Bendele A, Smith DA, Hamilton JA. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis 1997; 56(6): 364-8.
[http://dx.doi.org/10.1136/ard.56.6.364] [PMID: 9227165]
[118]
Lang RA, Metcalf D, Cuthbertson RA, et al. Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell 1987; 51(4): 675-86.
[http://dx.doi.org/10.1016/0092-8674(87)90136-X] [PMID: 3499986]
[119]
Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol 1998; 161(7): 3639-44.
[http://dx.doi.org/10.4049/jimmunol.161.7.3639] [PMID: 9759887]
[120]
Hua F, Henstock PV, Tang B. ERK activation by GM-CSF reduces effectiveness of p38 inhibitor on inhibiting TNFα release. Int Immunopharmacol 2010; 10(7): 730-7.
[http://dx.doi.org/10.1016/j.intimp.2010.04.002] [PMID: 20398804]
[121]
Espelin CW, Goldsipe A, Sorger PK, Lauffenburger DA, de Graaf D, Hendriks BS. Elevated GM-CSF and IL-1β levels compromise the ability of p38 MAPK inhibitors to modulate TNFα levels in the human monocytic/macrophage U937 cell line. Mol Biosyst 2010; 6(10): 1956-72.
[http://dx.doi.org/10.1039/c002848g] [PMID: 20617251]
[122]
van Nieuwenhuijze AEM, van de Loo FA, Walgreen B, et al. Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-κB ligand, and matrix metalloproteinases and drives bone and cartilage pathology in experimental arthritis: rationale for combination therapy in rheumatoid arthritis. Arthritis Res Ther 2015; 17(1): 163.
[http://dx.doi.org/10.1186/s13075-015-0683-5] [PMID: 26081345]
[123]
Plater-Zyberk C, Joosten L A B, Helsen MMA, Koenders MI, Baeuerle PA, van den Berg WB. Combined blockade of granulocyte-macrophage colony stimulating factor and interleukin 17 pathways potently suppresses chronic destructive arthritis in a tumour necrosis factor α-independent mouse model. Ann Rheum Dis 2009; 68(5): 721-8.
[http://dx.doi.org/10.1136/ard.2007.085431] [PMID: 18495731]
[124]
Pereira J, Velloso EDRP, Loterio HA, Laurindo IMM, Chamone DAF. Long-term remission of neutropenia in Felty’s syndrome after a short GM-CSF treatment. Acta Haematol 1994; 92(3): 154-6.
[http://dx.doi.org/10.1159/000204209] [PMID: 7871957]
[125]
Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, Stern AC, Vellenga E. Correction of granulocytopenia in Felty’s syndrome by granulocyte- macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood 1989; 74(8): 2769-70.
[http://dx.doi.org/10.1182/blood.V74.8.2769.2769] [PMID: 2510837]
[126]
De Vries egE, Willemse PHB, Biesma B, Stern AC, Limburg PC, Vellenga E. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy. Lancet 1991; 338(8765): 517-8.
[http://dx.doi.org/10.1016/0140-6736(91)90594-F] [PMID: 1678479]
[127]
Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F. Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study. Ann Rheum Dis 2011; 70(9): 1542-9.
[http://dx.doi.org/10.1136/ard.2010.146225] [PMID: 21613310]
[128]
Burmester GR, Weinblatt ME, McInnes IB, et al. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis 2013; 72(9): 1445-52.
[http://dx.doi.org/10.1136/annrheumdis-2012-202450] [PMID: 23234647]
[129]
Takeuchi T, Tanaka Y, Close D, Godwood A, Wu CY, Saurigny D. Efficacy and safety of mavrilimumab in Japanese subjects with rheumatoid arthritis: Findings from a Phase IIa study. Mod Rheumatol 2015; 25(1): 21-30.
[http://dx.doi.org/10.3109/14397595.2014.896448] [PMID: 24720551]
[130]
Burmester GR, McInnes IB, Kremer J, et al. A randomised phase IIb study of mavrilimumab, a novel GM–CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis 2017; 76(6): 1020-30.
[http://dx.doi.org/10.1136/annrheumdis-2016-210624] [PMID: 28213566]
[131]
Weinblatt ME, McInnes IB, Kremer JM, et al. A randomized phase II b study of mavrilimumab and golimumab in rheumatoid arthritis. Arthritis Rheumatol 2018; 70(1): 49-59.
[http://dx.doi.org/10.1002/art.40323] [PMID: 28941039]
[132]
Burmester GR, McInnes IB, Kremer JM, et al. Mavrilimumab, a fully human granulocyte–macrophage colony-stimulating factor receptor α monoclonal antibody. Arthritis Rheumatol 2018; 70(5): 679-89.
[http://dx.doi.org/10.1002/art.40420] [PMID: 29361199]
[133]
Kivitz A, Hazan L, Hoffman K, Wallin BA. FRI0209 MORAb-022, an anti-granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody (MAB): Results of the first study in patients with mild-to-moderate rheumatoid arthritis. Ann Rheum Dis 2016; 75: 507-7.
[134]
Behrens F, Tak PP, Østergaard M, et al. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis 2015; 74(6): 1058-64.
[http://dx.doi.org/10.1136/annrheumdis-2013-204816] [PMID: 24534756]
[135]
Genovese MC, Berkowitz M, Conaghan PG, et al. MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatol 2020; 2(11): e666-76.
[http://dx.doi.org/10.1016/S2665-9913(20)30224-1]
[136]
Buckley CD, Simón-Campos JA, Zhdan V, et al. Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study. Lancet Rheumatol 2020; 2(11): e677-88.
[http://dx.doi.org/10.1016/S2665-9913(20)30229-0]
[137]
Buckley C, Campos JS, Zhdan V, Becker B, Chauhan D, Davy K, et al. OP0228 GSK3196165 An investigational anti-gm-csf monoclonal antibody, improves patient reported outcomes in a phase iib study of patients with rheumatoid arthritis. Ann Rheum Dis 2019; 78(2): 191-1.
[138]
Huizinga TWJ, Batalov A, Stoilov R, et al. Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis. Arthritis Res Ther 2017; 19(1): 53.
[http://dx.doi.org/10.1186/s13075-017-1267-3] [PMID: 28274253]
[139]
Taylor PC, Saurigny D, Vencovsky J, et al. Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial. Arthritis Res Ther 2019; 21(1): 101.
[http://dx.doi.org/10.1186/s13075-019-1879-x] [PMID: 30999929]
[140]
Neklesa TK, Winkler JD, Crews CM. Targeted protein degradation by PROTACs. Pharmacol Ther 2017; 174: 138-44.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.027] [PMID: 28223226]
[141]
Martín-Acosta P, Xiao X. PROTACs to address the challenges facing small molecule inhibitors. Eur J Med Chem 2021; 210: 112993.
[http://dx.doi.org/10.1016/j.ejmech.2020.112993] [PMID: 33189436]
[142]
Saraswat AL, Vartak R, Hegazy R, Patel A, Patel K. Drug delivery challenges and formulation aspects of proteolysis targeting chimera (PROTACs). Drug Discov Today 2023; 28(1): 103387.
[http://dx.doi.org/10.1016/j.drudis.2022.103387] [PMID: 36184017]
[143]
Kargbo RB. PROTAC-mediated degradation of janus kinase as a therapeutic strategy for cancer and rheumatoid arthritis. ACS Med Chem Lett 2021; 12(6): 945-6.
[144]
Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release 2012; 161(2): 505-22.
[145]
Ha YJ, Lee SM, Mun CH, et al. Methotrexate-loaded multifunctional nanoparticles with near-infrared irradiation for the treatment of rheumatoid arthritis. Arthritis Res Ther 2020; 22(1): 146.
[http://dx.doi.org/10.1186/s13075-020-02230-y] [PMID: 32552859]
[146]
Yang Y, Guo L, Wang Z, et al. Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis and Re-polarization. Biomaterials 2021; 264: 120390.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120390] [PMID: 32980634]
[147]
Qian G, Zhang L, Shuai Y, et al. 3D-printed CuFe2O4-MXene/PLLA antibacterial tracheal scaffold against implantation-associated infection. Appl Surf Sci 2023; 614: 156108.
[http://dx.doi.org/10.1016/j.apsusc.2022.156108]
[148]
Qian G, Lu T, Zhang J, et al. Promoting bone regeneration of calcium phosphate cement by addition of PLGA microspheres and zinc silicate via synergistic effect of in-situ pore generation, bioactive ion stimulation and macrophage immunomodulation. Appl Mater Today 2020; 19: 100615.
[http://dx.doi.org/10.1016/j.apmt.2020.100615]
[149]
Qian G, Wang J, Yang L, et al. A pH-responsive CaO2@ZIF-67 system endows a scaffold with chemodynamic therapy properties. J Mater Sci 2023; 58(3): 1214-28.
[http://dx.doi.org/10.1007/s10853-022-08103-w]
[150]
Zhang H, Wang L, Cui J, et al. Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression. Sci Adv 2023; 9(14): eabo7868.
[http://dx.doi.org/10.1126/sciadv.abo7868] [PMID: 37018403]
[151]
Srour M, Alsuliman T, Labreuche J, et al. Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant 2023; 58(4): 401-6.
[http://dx.doi.org/10.1038/s41409-022-01898-x] [PMID: 36624161]
[152]
Wada F, Kondo T, Yamamoto R, Yamagiwa T, Arai Y, Mizumoto C. Addition and drug monitoring of mycophenolate mofetil for GVHD prophylaxis in unrelated bone marrow transplantation. Bone Marrow Transplant 2022; 57(7): 1198-200.
[http://dx.doi.org/10.1038/s41409-022-01692-9]
[153]
Elhadad S, Chadburn A, Magro C, Van Besien K, Roberson EDO, Atkinson JP. C5b-9 and MASP2 deposition in skin and bone marrow microvasculature characterize hematopoietic stem cell transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 2022; 57(9): 1445-7.
[http://dx.doi.org/10.1038/s41409-022-01723-5]
[154]
Pandrowala A, Ganatra P, Krishnan VP, et al. Narsoplimab for severe transplant-associated thrombotic microangiopathy. Thromb J 2023; 21(1): 26.
[http://dx.doi.org/10.1186/s12959-023-00464-9] [PMID: 36915123]

Rights & Permissions Print Cite
Article Metrics
59
2
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
World Prematurity Day
© 2024 Bentham Science Publishers | Privacy Policy