Top

Published in:

Open Access 01-04-2024 | Lichen Planus | ORIGINAL PAPER

Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case–control study

Authors: Maha Fathy Elmasry, Rana Ahmed Mosaad, Omar Ahmed Azzam, Laila Ahmed Rashed, Aya Fahim

Published in: Archives of Dermatological Research | Issue 3/2024

Abstract

Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case–control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.

Available only for authorised users

Solimani F, Forchhammer S, Schloegl A, Ghoreschi K, Meier K (2021) Lichen planus - a clinical guide. J Dtsch Dermatol Ges 19(6):864–882. https://doi.org/10.1111/ddg.14565CrossRefPubMed

Boch K, Langan EA, Kridin K, Zillikens D, Ludwig RJ, Bieber K (2021) Lichen Planus Front Med (Lausanne) 8:737813. https://doi.org/10.3389/fmed.2021.737813CrossRefPubMed

Plazyo O, Shao S, Gudjonsson JE (2021) IFN-γ signaling in lichen planus. Glob Clin Transl Res 3(1):1–6. https://doi.org/10.36316/gcatr.03.0039CrossRef

Costa NL, Gonçalves JAM, de Lima SLG, de Arruda JAA, Miranda ACC, Mesquita RA, da Silveira ÉJD, Batista AC (2020) Evaluation of PD-L1, PD-L2, PD-1 and cytotoxic immune response in oral lichen planus. Oral Dis 26(6):1246–1254. https://doi.org/10.1111/odi.13344CrossRefPubMed

Ghosh C, Luong G, Sun Y (2021) A snapshot of the PD-1/PD-L1 pathway. J Cancer 12(9):2735–2746. https://doi.org/10.7150/jca.57334CrossRefPubMedPubMedCentral

Wei SC, Duffy CR, Allison JP (2018) Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov 8(9):1069–1086. https://doi.org/10.1158/2159-8290.CD-18-0367CrossRefPubMed

Iaccarino A, Salatiello M, Migliatico I, De Luca C, Gragnano G, Russo M, Bellevicine C, Malapelle U, Troncone G, Vigliar E (2021) PD-L1 and beyond: immuno-oncology in cytopathology. Cytopathology 32(5):596–603. https://doi.org/10.1111/cyt.12982CrossRefPubMedPubMedCentral

Larsen TV, Hussmann D, Nielsen AL (2019) PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer. Cancer Commun (Lond) 39(1):30. https://doi.org/10.1186/s40880-019-0376-6CrossRefPubMed

Sharpe AH, Pauken KE (2018) The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 18(3):153–167. https://doi.org/10.1038/nri.2017.108CrossRefPubMed

10.

Chang HC, Chang YS, Lee HL, Lin MH (2020) Bullous lichen planus-like reactions in a patient with renal cancer after receiving anti-programmed cell death-1 therapy. Dermatol Sin 38(1):55–58. https://doi.org/10.4103/ds.ds_17_19CrossRef

11.

Sugawara A, Koga H, Abe T, Ishii N, Nakama T (2021) Lichen planus-like lesion preceding bullous pemphigoid development after programmed cell death protein-1 inhibitor treatment. J Dermatol 48(3):401–404. https://doi.org/10.1111/1346-8138.15693CrossRefPubMed

12.

Wat M, Mollanazar NK, Ellebrecht CT, Forrestel A, Elenitsas R, Chu EY (2022) Lichen-planus-pemphigoides-like reaction to PD-1 checkpoint blockade. J Cutan Pathol 49(11):978–987. https://doi.org/10.1111/cup.14299CrossRefPubMed

13.

Simonsen AB, Kaae J, Ellebaek E, Svane IM, Zachariae C (2020) Cutaneous adverse reactions to anti-PD-1 treatment-A systematic review. J Am Acad Dermatol 83(5):1415–1424. https://doi.org/10.1016/j.jaad.2020.04.058CrossRefPubMed

14.

Bhardwaj M, Chiu MN, Pilkhwal Sah S (2022) Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance. Cutan Ocul Toxicol 41(1):73–90. https://doi.org/10.1080/15569527.2022.2034842CrossRefPubMed

15.

Cetinözman F, Jansen PM, Vermeer MH, Willemze R (2012) Differential expression of programmed death-1 (PD-1) in Sézary syndrome and mycosis fungoides. Arch Dermatol 148(12):1379–1385. https://doi.org/10.1001/archdermatol.2012.2089CrossRefPubMed

16.

Nagui NAR, Sayed KS, Rashed LA, El Sayed H (2018) Expression of soluble and membrane-bound programmed death protein 1 in psoriasis vulgaris patients: a case-controlled study. J Egypt Women’s Dermatol Soc 15(1):10–14. https://doi.org/10.1097/01.EWX.0000527924.92973CrossRef

17.

Awad SS, Touni AA, Gabril MY (2020) Expression of immune checkpoints in active nonsegmental vitiligo: a pilot study. Int J Dermatol 59(8):982–988. https://doi.org/10.1111/ijd.14983CrossRefPubMed

18.

Ernst N, Friedrich M, Bieber K, Kasperkiewicz M, Gross N, Sadik CD, Zillikens D, Schmidt E, Ludwig RJ, Hartmann K (2021) Expression of PD-1 and Tim-3 is increased in skin of patients with bullous pemphigoid and pemphigus vulgaris. J Eur Acad Dermatol Venereol 35(2):486–492. https://doi.org/10.1111/jdv.16780CrossRefPubMed

19.

Kaur H, Nikam BP, Jamale VP, Kale MS (2020) Lichen Planus Severity Index: A new, valid scoring system to assess the severity of cutaneous lichen planus. Indian J Dermatol Venereol Leprol 86(2):169–175. https://doi.org/10.4103/ijdvl.IJDVL_650_17CrossRefPubMed

20.

Aghamajidi A, Raoufi E, Parsamanesh G, Jalili A, Salehi-Shadkami M, Mehrali M, Mohsenzadegan M (2021) The attentive focus on T cell-mediated autoimmune pathogenesis of psoriasis, lichen planus and vitiligo. Scand J Immunol 93(4):e13000. https://doi.org/10.1111/sji.13000CrossRefPubMed

21.

Wang Y, Wei M, Wang Y, Liu Y, Wang X (2023) The critical role of IFNγ in the epidermotropic migration of lymphocytes in oral lichen planus. J Oral Pathol Med 52(1):72–80. https://doi.org/10.1111/jop.13383CrossRefPubMed

22.

Qin W, Hu L, Zhang X, Jiang S, Li J, Zhang Z, Wang X (2019) The diverse function of PD-1/PD-L pathway beyond cancer. Front Immunol 10:2298. https://doi.org/10.3389/fimmu.2019.02298CrossRefPubMedPubMedCentral

23.

Andrews LP, Yano H, Vignali DAA (2019) Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups. Nat Immunol 20(11):1425–1434. https://doi.org/10.1038/s41590-019-0512-0CrossRefPubMed

24.

Bottlaender L, Amini-Adle M, Maucort-Boulch D, Robinson P, Thomas L, Dalle S (2020) Cutaneous adverse events: a predictor of tumour response under anti-PD-1 therapy for metastatic melanoma, a cohort analysis of 189 patients. J Eur Acad Dermatol Venereol 34(9):2096–2105. https://doi.org/10.1111/jdv.16311CrossRefPubMed

25.

Shirouchi K, Koshikawa S, Shinya K, Watanabe H, Izumi M, Yoshimura K, Sueki H (2021) Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors. J Dermatol 48(9):1428–1432. https://doi.org/10.1111/1346-8138.15977CrossRefPubMed

26.

Zhou G, Zhang J, Ren XW, Hu JY, Du GF, Xu XY (2012) Increased B7–H1 expression on peripheral blood T cells in oral lichen planus correlated with disease severity. J Clin Immunol 32(4):794–801. https://doi.org/10.1007/s10875-012-9683-2CrossRefPubMed

27.

Carty SA, Riese MJ, Koretzky GA (2018) T-cell immunity. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, Salama ME, Abutalib SA (eds) Hematology, 7th edn. Elsevier, Amsterdam, The Netherlands, pp 221–239CrossRef

28.

Shao S, Tsoi LC, Sarkar MK, Xing X, Xue K, Uppala R, Berthier CC, Zeng C, Patrick M, Billi AC, Fullmer J, Beamer MA, Perez-White B, Getsios S, Schuler A, Voorhees JJ, Choi S, Harms P, Kahlenberg JM, Gudjonsson JE (2019) IFN-γ enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus. Sci Transl Med 11(511):eaav7561. https://doi.org/10.1126/scitranslmed.aav7561CrossRefPubMedPubMedCentral

29.

Grän F, Kerstan A, Serfling E, Goebeler M, Muhammad K (2020) Current developments in the immunology of psoriasis. Yale J Biol Med 93(1):97–110PubMedPubMedCentral

30.

Harris JE (2015) IFN-γ in vitiligo, is it the fuel or the fire? Acta Derm Venereol 95(6):643–644. https://doi.org/10.2340/00015555-2137CrossRefPubMed

31.

Kim DS, Je JH, Kim SH, Shin D, Kim TG, Kim DY, Kim SM, Lee MG (2015) Programmed death-ligand 1, 2 expressions are decreased in the psoriatic epidermis. Arch Dermatol Res 307(6):531–538. https://doi.org/10.1007/s00403-015-1588-5CrossRefPubMed

32.

Bartosińska J, Michalak-Stoma A, Kowal M, Raczkiewicz D, Krasowska D, Chodorowska G, Giannopoulos K (2019) Analysis of circulating soluble programmed death 1 (PD-1), neuropilin 1 (NRP-1) and human leukocyte antigen-G (HLA-G) in psoriatic patients. Postepy Dermatol Alergol 36(2):167–172. https://doi.org/10.5114/ada.2018.73329CrossRefPubMed

33.

Willemsen M, Melief CJM, Bekkenk MW, Luiten RM (2020) Targeting the PD-1/PD-L1 axis in human vitiligo. Front Immunol 11:579022. https://doi.org/10.3389/fimmu.2020.579022CrossRefPubMedPubMedCentral

34.

Ibrahim SM (2021) Study of lichen planus variants and an overview of available management. Eur J Mol Clin Med 8(3):3434–3441

35.

Shimada Y, Hayashi M, Nagasaka Y, Ohno-Iwashita Y, Inomata M (2009) Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4⁺ T cells. Exp Gerontol 44(8):517–522. https://doi.org/10.1016/j.exger.2009.05.003CrossRefPubMed

36.

Lee KA, Shin KS, Kim GY, Song YC, Bae EA, Kim IK, Koh CH, Kang CY (2016) Characterization of age-associated exhausted CD8⁺ T cells defined by increased expression of Tim-3 and PD-1. Aging Cell 15(2):291–300. https://doi.org/10.1111/acel.12435CrossRefPubMedPubMedCentral

Title: Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case–control study
Authors: Maha Fathy Elmasry
Rana Ahmed Mosaad
Omar Ahmed Azzam
Laila Ahmed Rashed
Aya Fahim
Publication date: 01-04-2024
Publisher: Springer Berlin Heidelberg
Keywords: Lichen Planus
Vulgar Psoriasis
Published in: Archives of Dermatological Research / Issue 3/2024
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-024-02838-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case–control study

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2024

The potential cutaneous benefits of edible bird’s nest

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in psoriasis: a systematic review and meta-analysis

Why different types of patients seek cosmetic treatments

Lack of minority enrollment in lasers for tattoo removal clinical trials: a cross‐sectional analysis and call to action

An approach to diagnosis and management of patients with pyoderma gangrenosum from an international perspective: results from an expert forum

Patient perspectives on topical minoxidil for hair loss: a survey-based study from the University of Michigan Alopecia Clinic