Transcription factor NF-kB in the prognosis of outcomes for patients undergoing repeat keratoplasty
DOI:
https://doi.org/10.31288/oftalmolzh202121622Keywords:
keratoplasty, graft opacification, immunophenotyping, transcription factor NF-kBAbstract
Background: Obtaining a clear graft after repeat keratoplasty is still a challenging task for corneal transplant surgeons. Corneal transplant rejection rate is significantly increased in repeat keratoplasty compared with first keratoplasty. Activation of nuclear factor kappa B (NF-kB) plays a key role in the pathogenesis of rejection of transplants of various organs and tissues, primarily due to production of proinflammatory cytokines (TNF, IL-1, etc.).
Purpose: To assess the role of transcription factor NF-kB in lymphocyte subsets in the prognosis of outcomes for patients undergoing repeat keratoplasty.
Material and Methods: Forty-six patients (46 eyes) who underwent repeat keratoplasty were included. Of these, 30 patients (group 1) developed an opacified graft, and 16 (group 2) obtained a clear graft. Patient age ranged from 32 to 88 years. Imaging flow cytometry (ImageStream Mark II – AMNIS) and Amnis NF-kB Translocation Kits (ACS10000, Millipore, Sigma) were used to assess percentages of the cells with translocation of the NF-kB p65 subunit for lymphocyte subsets. Statistical analyses were conducted using Statistica 13.0 (StatSoft, Tulsa, OK, USA) software. The Mann–Whitney test was used to assess significance of differences.
Results: Percentages of the cells with translocation of the NF-kB p65 subunit were higher in group 1 compared with group 2, particularly, for T-helpers (26.5[17; 29] vs 12.2[11;21]; p=0.003), cytotoxic T-cells (24.0[17;28] vs 11.5[7;15]; p=0.006), NK cells (45.0[34;53] vs 18.2[16;39]; p=0.014), Th17 cells (23.9[18;31] vs 14.3[12;21]; p=0.002), regulatory T cells (30.4[21;34] vs 17.4[16;22]; p=0.001) and activated T helpers (21.918;28] vs 11.4[11;17]; p=0.002).
Conclusion: There were substantially increased percentages of activated cells in lymphocyte subsets (with the most pronounced increase for NK cells) of patients who developed an opacified graft compared to those who obtained a clear graft following re-keratoplasty. Assessment of percentages of the cells with translocation of the NF-kB p65 subunit for lymphocyte subsets provides valuable information for predicting graft rejection following re-keratoplasty.
References
1.Perez VL. Visualization of immune responses in the cornea. Cornea. 2017 Nov;36 Suppl 1:S5-S8.https://doi.org/10.1097/ICO.0000000000001354
2.Neroev VV, Balatskaya NV, Chentsova EV, Shamkhalova KhM. [Mechanisms of immune regulation and transplantation immunity in corneal transplants]. Medical Immunology (Russia)/Meditsinskaia Immunologiia. 2020; 22(1): 61-76. Russian.https://doi.org/10.15789/1563-0625-MOI-1768
3.Kitazava K, Wakimasu K, Kayukawa K, Yokota I, Inatomi T, Hieda O, et al. Moderately long-term safety and efficacy of repeat penetrating keratoplasty. Cornea. 2018 Oct;37(10):1255-9.https://doi.org/10.1097/ICO.0000000000001694
4.Kuncevich NV. [Role of nuclear factor NF-kB in graft rejection]. Vestnik transplantologii i iskusstvennykh organov. 2017;12;1:72-7. Russian.
5.Liu T, Zhang L, Joo D, Sun SC. NF-kB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023.https://doi.org/10.1038/sigtrans.2017.23
6.Sun SC, Chang JH, Jin J. Regulation of nuclear factor-κB in autoimmunity. Trends Immunol. 2013 Jun;34(6):282-9.https://doi.org/10.1016/j.it.2013.01.004
7.Yue Y, Stone S, Lin W. Role of nuclear factor κB in multiple sclerosis and experimental autoimmune encephalomyelitis. Neural Regen Res. 2018 Sep;13(9):1507-15.https://doi.org/10.4103/1673-5374.237109
8.Park MH, Hong JT. Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches. Cells. 2016 Mar 29;5(2):15.https://doi.org/10.3390/cells5020015
9.Troulfas G, Geller DA. NF‐κB in transplantation: friend or foe? Transpl Infect Dis. 2001 Dec;3(4):212-9.https://doi.org/10.1034/j.1399-3062.2001.30405.x
10.Serasanambati M, Chilakapati SR. Function of Nuclear Factor Kappa B (NF-kB) in Human Diseases-A Review. South Indian J Biol Sci. 2016;2:368.https://doi.org/10.22205/sijbs/2016/v2/i4/103443
11.Patent RF, MPK G01 № 33/53, G01 № 33/50. [Method for measuring the mitochondrial activity of lymphocytes]. Petrichuk SV, Izmailova TD, Radygina TV. The applicant and patent holder is the National Medical Research Center for Children's Health of the Russian Ministry of Health. № 2005141145/15; declared 28.12.2005; published 10.07.2007. Russian.
12.Sommerwerck U, Lindemann M, Kleibrink BE, Rabis T, Weinreich G, Kamler M, et al. NF-kB location in T-cells is promising to monitor immunosuppression after lung transplantation. Eur Resp J. Sep 2014; 44 (Suppl 58):3309.
13.Onishchenko NA, Bashkina LV, Nikolskaia AO, Artamonov SD. [Informative value of CD4 monitoring for the diagnosis and prognosis of host-graft response]. Vestnik transplantologii i iskusstvennykh organov. 2013; 15(4): 112-25. Russianhttps://doi.org/10.15825/1995-1191-2013-4-112-125
14.Komakh YA, Borzenok SA, Petrichuk SV, Samokhina IV. [Corneal graft rejection: clinical-and-anamnestic and immunological criteria for diagnosis]. Rossiiskii Immunologicheskii Zhurnal. 2017;11(20);4:714-716. Russian.
15.Albensi BC. What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion? Front Cell Dev Biol. 2019 Aug 7;7:154.https://doi.org/10.3389/fcell.2019.00154
16.Angajala A, Lim S, Phillips JB, Kim J-H, Yates C, You Z, Tan M. Diverse roles of mitochondria in immune responses: novel insights into immune-metabolism. Front Immunol. 2018 Jul 12;9:1605. https://doi.org/10.3389/fimmu.2018.01605
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