Büllöz pemfigoidli hastalarda serum ve lezyonel miRNA-1291 ekspresyonlarının karşılaştırılması

Year 2022, Volume: 15 Issue: 4, 836 - 844, 01.10.2022

Şule Subaşı Gökşin , Buket Er Urgancı , Işıl Göğem İmren , İbrahim Açıkbaş

https://doi.org/10.31362/patd.1174388

Abstract

Amaç: Büllöz pemfigoid (BP), yaşla birlikte artan otoimmün bir hastalıktır. miRNA-1291, birçok immün aracılı kutanöz hastalıkta önemli rol oynayan bir mikroRNA'dır. Serum ve lezyonlu derideki ekspresyon seviyelerini ve ana BP biyobelirteçleri (anti-BP180 ve anti-BP230) ve CCL17 ile korelasyonunu karşılaştırarak miRNA-1291'in BP'deki rolünü araştırmayı amaçladık.
Gereç ve yöntem: BP'li 23 hasta ve 23 sağlıklı kontrol hastası çalışmaya dahil edildi. Serum ve biyopsi örneklerinden RNA izolasyonu için miRNeasy Mini Kitleri kullanıldı. cDNA'nın dönüştürülmesi için Qiagen-miRCURY LNA RT Kiti kullanıldı. miRNA-1291 ekspresyonu, orijinal primer ve SYBR Green ana karışımı ile Real-Time PCR ile gerçekleştirildi. Serum CCL17, anti-BP180 ve anti-BP230 seviyeleri ELISA kullanılarak ölçüldü. İstatistiksel değerlendirme için SPSS 25.0 (IBM SPSS Statistics 25 yazılımı) kullanıldı.
Bulgular: Serum ve biyopsi örneklerinde miRNA-1291 ekspresyonu, kontrol grubuna göre sırasıyla 7.02 ve 4.77 kat anlamlı şekilde up-regüleydi (p=0,001, p=0.007). BP ve CCL17 hastalarında anti-BP-180, anti-BP-230 serum düzeyleri kontrol grubuna göre anlamlı derecede yüksekti (p=0,0049, p=0,0071, p=0,001). BP hastalarında anti-BP180, anti-BP230, CCL17 seviyeleri, serum miRNA-1291 ekspresyonu ile pozitif korelasyon gösterdi. Ek olarak, serum miRNA-1291 ekspresyonu, lezyonel miRNA-1291 ekspresyonu ile iyi korele idi.
Sonuç: Serum ve lezyonlu dokuda lezyonlu olmayan dokuya göre miRNA-1291 düzeylerinin artması, miRNA-1291'in BP'nin patogenezinde rol oynayabileceğini düşündürmektedir. miRNA-1291 diğer BP biyobelirteçleri ile korelasyon gösterdiğinden, BP için önemli bir biyobelirteç olarak hizmet edebilir.

Keywords

Büllöz pemfigoid, , biyobelirteç, miRNA-1291, BP180, CCL17

Supporting Institution

Pamukkale Üniversitesi

Project Number

2020BSP20

Comparison of serum and lesional miRNA-1291 expressions in patients with bullous pemphigoid

Abstract

Purpose: Bullous pemphigoid (BP) is an autoimmune disease increasing by age. miRNA-1291 is a microRNA that plays major role in many immune-mediated cutaneous diseases. We aimed to investigate the role of miRNA-1291 in BP by comparing its expression levels in serum and lesional skin and its correlation with main BP biomarkers (anti-BP180, and anti-BP230) and CCL17
Materials and methods: Twenty three patients with BP and 23 healthy control patients were included in the study. The miRNeasy Mini Kits was used for RNA isolation from serum and biopsy samples. Qiagen-miRCURY LNA RT Kit was used for conversion of cDNA. miRNA-1291 expression was performed by Real-Time PCR with the original primer and SYBR Green master mix. Serum CCL17, anti-BP180, and anti-BP230 levels were measured with use of ELISA. SPSS 25.0 (IBM SPSS Statistics 25 software) was used for statistical evaluation.
Results: The expression of miRNA-1291 in serum and biopsy samples were 7.02 and 4.77-fold significantly upregulated than that of control group respectively (p=0.001, p=0.007). The serum levels of anti-BP-180, anti-BP-230 and CCL17 in BP patients were significantly higher compared to control group (p=0.0049, p=0.0071, p=0.001). Anti-BP180, anti-BP230, CCL17 levels and serum miRNA-1291 expression were correlated positively in BP patients. Additionally, serum miRNA-1291 expression were correlated well with lesional miRNA-1291 expression.
Conclusion: The increase in miRNA-1291 levels in serum and lesional tissue compared to non-lesional tissue suggests that miRNA-1291 may play a role in the pathogenesis of BP. As miRNA-1291 correlates with other BP biomarkers, it may serve as an important biomarker for BP.

Keywords

Bullous pemphigoid, biomarker, miRNA-1291, BP180, CCL17

Project Number

2020BSP20

References

• 1. Zhao CY, Murrell DF. Outcome measures for autoimmune blistering diseases. J Dermatol 2015;42:31-36. https://doi.org/10.1111/1346-8138.12711
• 2. Sonkoly E, Ståhle M, Pivarcsi A. MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol 2008;33:312-315. https://doi.org/10.1111/j.1365-2230.2008.02804.x
• 3. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 2012;4:143-159. https://doi.org/10.1002/emmm.201100209. Epub 2012 Feb 20. Erratum in: EMBO Mol Med 2017;9:852.
• 4. Chen JQ, Papp G, Szodoray P, Zeher M. The role of microRNAs in the pathogenesis of autoimmune diseases. Autoimmun Rev 2016;15:1171-1180. https://doi.org/10.1016/j.autrev.2016.09.003
• 5. Genovese G, Di Zenzo G, Cozzani E, Berti E, Cugno M, Marzano AV. New ınsights into the pathogenesis of bullous pemphigoid: 2019 Update. Front Immunol 2019;10:1506. https://doi.org/10.3389/fimmu.2019.01506
• 6. Chiorean RM, Baican A, Mustafa MB. et al. Complement-activating capacity of autoantibodies correlates with disease activity in bullous pemphigoid patients. Front Immunol 2018;9:2687. https://doi.org/10.3389/fimmu.2018.02687
• 7. Amber KT, Murrell DF, Schmidt E, Joly P, Borradori L. Autoimmune subepidermal bullous diseases of the skin and mucosae: Clinical features, diagnosis, and management. Clin Rev Allergy Immunol 2018;54:26-51. https://doi.org/10.1007/s12016-017-8633-4
• 8. Liu Y, Li L, Xia Y. BP180 is critical in the autoimmunity of bullous pemphigoid. Front Immunol 2017;8:1752. https://doi.org/10.3389/fimmu.2017.01752
• 9. Feliciani C, Caldarola G, Kneisel A. et al. IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses. Br J Dermatol 2009;161:306-312. https://doi.org/10.1111/j.1365-2133.2009.09266.x
• 10. Qiu L, Zhang L, Qi R, Gao X, Chen H, Xiao T. miR-1291 Functions as a potential serum biomarker for bullous pemphigoid. Dis Markers 2020;2020:9505312. https://doi.org/10.1155/2020/9505312
• 11. Marazza G, Pham HC, Schärer L. et al. Autoimmune bullous disease Swiss study group. Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study. Br J Dermatol 2009;161:861-868. https://doi.org/10.1111/j.1365-2133.2009.09300.x
• 12. Bakay ÖSK. Kronik spontan ürtiker ile microrna-221, microrna-155 ve IL-31 ilişkisinin araştırılması - Investigation of relationship between chronic spontaneous urticaria with microrna-221, micorna-155 and IL-31. https://tez.yok.gov.tr/UlusalTezMerkezi/tezSorguSonucYeni.jsp Erişim tarihi 20 Ağustos 2022
• 13. Zurawska A, Mycko MP, Selmaj KW. Circular RNAs as a novel layer of regulatory mechanism in multiple sclerosis. J Neuroimmunol 2019 15;334:576971. https://doi.org/10.1016/j.jneuroim.2019.576971
• 14. Juczynska K, Wozniacka A, Waszczykowska E. et al. Expression of the jak/stat signaling pathway in bullous pemphigoid and dermatitis herpetiformis. Mediators Inflamm 2017;2017:6716419. https://doi.org/10.1155/2017/6716419
• 15. Muramatsu K, Ujiie H, Kobayashi I. et al. Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects. J Allergy Clin Immunol 2018;142:1818-1830.e6. https://doi.org/10.1016/j.jaci.2018.03.014
• 16. Vestergaard C, Deleuran M, Gesser B, Larsen CG. Thymus- and activation-regulated chemokine (TARC/CCL17) induces a Th2-dominated inflammatory reaction on intradermal injection in mice. Exp Dermatol 2004;13:265-271. https://doi.org/10.1111/j.0906-6705.2004.00149.x
• 17. Tamaki K, Kakinuma T, Saeki H. et al. Serum levels of CCL17/TARC in various skin diseases. J Dermatol 2006;33:300-302. https://doi.org/10.1111/j.1346-8138.2006.00072.x
• 18. Kakinuma T, Wakugawa M, Nakamura K, Hino H, Matsushima K, Tamaki K. High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid. Br J Dermatol 2003;148:203-210. https://doi.org/10.1046/j.1365-2133.2003.05066.x
• 19. Saeki H, Tamaki K. Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J Dermatol Sci 2006;43:75-84
• 20. Echigo T, Hasegawa M, Shimada Y, Inaoki M, Takehara K, Sato S. Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases. Arch Dermatol Res 2006;298:38-45. https://doi.org/10.1007/s00403-006-0661-5
• 21. Suzuki M, Yamaguchi Y, Nakamura K. et al. Serum thymus and activation-regulated chemokine (TARC/CCL17) may be useful to predict the disease activity in patients with bullous pemphigoid. J Eur Acad Dermatol Venereol 2021;35:e121-e124. https://doi.org/10.1111/jdv.16851