AB1480 EXPRESSION OF JAK-STAT SIGNALING PATHWAY IN HIDRADENITIS SUPPURATIVA PATHOLOGICAL BIOPSY SPECIMENS

Abstract

BackgroundHidradenitis suppurativa (HS) is inflammatory skin disease with an unknown etiology. JAK-STAT pathway may be implicated in its pathogenesis. Considering the unmet need in the treatment of inflammatory skin diseases, assessment of the JAK/STAT pathway could provide new understanding in the pathogenesis of these disorders. Therefore, in this study we primarily intended to investigate this pathway in patients with HS.ObjectivesHerein we aimed to investigate the JAK/STAT signaling pathway in the skin biopsies of HS patients and compared with psoriasis (PSO) and healthy subject.MethodsThis study used human tissues of healthy (n=26) and diseased skin samples obtained from the psoriatic (n=35) and HS (n=25) patients. Immunohistochemical methods were used to evaluate the expression of JAK1, JAK2, JAK3, Tyrosine Kinase 2 (TYK2), STAT1, STAT3, STAT4, STAT5, and STAT6. In the dermis, the staining intensity was recorded as ‘positive’ or ‘negative. The epidermal part is divided into cytoplasmatic and nuclear parts and strong staining intensity recorded by staining in ≥50% of the cells.ResultsA total of 86 biopsies obtained from 25 HS (40.8 ±21.8 years, 60% male (M)), 35 PSO (46.5 ± 18.4 years, 57% M) and 26 control subjects (60.3 ± 18.3 years, 46% M) were analyzed. All JAK-STAT and TYK2 are overexpressed in dermal part of HS skin. TYK2, JAK3,STAT3 and STAT4 are strongly expressed in cytoplasmic part of epidermis in HS skin.TYK2, JAK3 and STAT1 is strongly expressed in nuclear part of epidermis in HS skin. JAK-STAT pathway is overexpressed in dermal part of psoriatic skin especially STAT2 and STAT6 but JAK1 is not expressed dermal part of psoriatic skin. All STATs and JAK1, JAK3 and TYK2 are strongly expressed in cytoplasmic part of epidermis in psoriatic skin. TYK2, JAK3 and STAT1 are strongly expressed in nuclear part of epidermis in psoriatic skin. The summary of the findings is given in Table 1. When look at the correlation analysis for TYK2 had strong correlation with HS according to control subjects in the dermal and nuclear staining. The summary of findings and the correlation analysis for HS, healty control (HC) and PSO is given in Table 1.ConclusionIn this study, we demonstrated an increased activity in the skin biopsies of HS. When considering the unmet need in the treatment of this disease current data is significant for guiding the possible future therapies.Reference[1] Frew JW, Hawkes JE, Krueger JG. A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa. F1000Research [Internet]. 2018 [cited 2022 Mar 25];7. Available from:/pmc/articles/PMC6392156/Table-1.Summary of the findings and the correlation between inflammatory skin diseases and JAK/STAT pathway staining in the skinHidradenitis Suppurativa (n=25)Psoriasis (n=35)Healthy skin (n=26)HS vs. HC*PSO vs. HS*Dermal stainingTYK223, (92)34, (97.1)00.92JAK13, (8.6)00JAK214, (56)21, (60)2, (7.7)0.52JAK323, (92)31, (88.6)00.92STAT116, (64)27, (77.1)00.69STAT225, (100)35, (100)14, (53.8)0.42STAT323, (92)34, (97.1)00.92STAT44, (16)11, (31.4)00.29STAT517, (68)27, (77.1)00.72STAT614, (56)33, (94.3)00.62-0.45Epidermal cytoplasmic staining in ≥50% of the cellsTYK22, (8)21, (60)8, (30.8)-0.69-0.58JAK18, (32)11, (31.4)0JAK325, (100)35, (100)26, (100)0.44STAT322, (88)34, (97.1)14, (53.8)0.37STAT415, (60)29, (82.9)14, (53.8)-0.25Epidermal nuclear cells with strong stainingTYK25, (20)27, (77.1)00.76-0.56JAK325, (100)35, (100)26, (100)STAT119, (76)31, (88.6)19, (73.1)* Note that “r” correlation coefficients were given in the cells which indicated significant correlations between the variables (p<0.05). Empty cells indicated no correlation (p>0.05) therefore “r” values were not provided.Acknowledgements:NIL.Disclosure of InterestsNone Declared.