42 5 th World Psoriasis & Psoriatic Arthritis Conference 2018
P100 IMMUNOLOGICAL MEMORY EXISTS IN THE RECURRENT LESION AND NONRECURRENT SKIN
AFTER REMISSION IN PSORIATIC PATIENTS Zhu Shen Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’ s Hospital
Introduction: Psoriasis usually recurs in previously affected areas, so a pathogenic memory has been proposed, but the nature of such site-specific recurrent memory is not completely known. Tissueresident memory T( TRM) cells are non-recirculating memory T cells that persist long-term in epithelial tissues, including the skin. Because they can localize in the skin for many months, we speculate that TRM may contribute to recurrent pathology of psoriasis. Objectives: The aim of the present study is to compare the differences of quantity proportion and secretion ability of cytokines of the TRM cells between recurrent and nonrecurrent lesions following remission, as well as to explicit the possible survival signal for these TRM cells in psoriatic lesion. Methods: RNA-Seq, Gene Ontology and KEGG analysis, real-time PCR, flow cytometer analysis / sorting, cell stimulation assay, and western blot were used to explore the immunological memory. Results: Compared with normal skin, there are common shared genes significantly upregulated( > 2 folds, p < 0.001) by recurrent and nonrecurrent lesions, including CD69. CD69 mRNA transcription level in nonrecurrent lesions after remission remains as high as in neighboring recurrent lesions. CD8 + CD69 + TRM cells exist in both lesions, and they can secret almost same amount of IL-17A and IL-22 after stimulation. Levels of IL-15, secreted by keratinocytes in psoriasis epidermis, in nonrecurrent lesions remain as high as in neighboring recurrent lesions, and recombinant human IL-15 can induce CD69 on TRM cells. Conclusions: Our preliminary study shows that CD8 + CD69 + TRM cells persist in clinically resolved psoriatic lesions whether it recurs or not, and they can produce IL-17A and IL-22 with critical effect on psoriatic recurrence and development. Furthermore, we have indicated the IL-15 may play crucial role in the survival of CD8 + CD69 + TRM cells in psoriatic lesions. References: 1. Mueller SN, Mackay LK. Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immunol. 2016 Feb; 16( 2): 79-89. 2. Clark RA. Resident memory T cells in human health and disease. Sci Transl Med. 2015 Jan 7; 7( 269): 269rv1. 3. Park CO, KupperTS. The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat Med. 2015 Jul; 21( 7): 688-97. 4. Cheuk S, Wikén M, Blomqvist L, Nylén S, Talme T, Ståhle M, EidsmoL. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014 Apr 1; 192( 7): 3111-20.
P101 INVESTIGATING SYSTEMIC INFLAMMATION AS THE COMMON LINK BETWEEN DEPRESSION, PSORIASIS,
AND PSORIATIC ARTHRITIS IN US VETERANS Samar Gupta 1, Alicja Wasilewski 2 University of Michigan 1, MI State 2
Introduction: Psychosocial factors are important in the onset and / or exacerbation of psoriasis in 40 % to 80 % of cases. Psoriasis has been associated with suicide, and an increased prevalence of alcoholism and a range of personality characteristics. A recent systematic meta-analysis of 98 eligible studies with a total of 401,703 psoriasis patients showed that patients with psoriasis were approximately one and a half times more likely to exhibit signs of depression compared with healthy controls. [ 1 ]. Emerging evidence suggests that depression, like psoriasis, is associated with systemic inflammation, and the systemic inflammatory profile of the two conditions show similar traits. Depression is considered to have a strong inflammatory component, similar to psoriasis, e. g. interleukin( IL)-2, IL-6, IL-12, and tumour necrosis factor( TNF)-α [ 2 – 5 ]. US Veteran population has increased incidence of mental health issue as compared to general population. making Veteran group a unique population that warrants investigation. Objectives: Hypotheses- 1 / Veterans with concomitant depression and psoriasis / PsA may have elevated inflammatory markers like CRP, ESR, and SPEP. 2 / Depression may improve with the treatment of psoriasis / psoriatic arthritis without antidepressant use. Methods: A 36-month retrospective chart review of 100 veterans with diagnosis of depression and psoriasis / psoriatic arthritis. Elevated inflammatory markers, including sedimentation rate, C-reactive protein( CRP) and serum protein electrophoresis( SPEP), as well as longitudinal disease course of depression( PHQ-8) and psoriasis / psoriatic arthritis( HAQ-DI); specifically disease activity, and depression symptoms will be assessed. We then aim to draw a correlation between disease activity and active depressive symptoms. Results: to be available Conclusions: to be available References: 1. Dowlatshahi EA, et al. The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and metaanalysis. J Invest Dermatol 2014; 134: 1542 – 1551. 2. Allison DJ, Ditor DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. J Neuroinflammation 2014; 11: 151. 3. Dantzer R, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9: 46 – 56. 4. Han Q-Q, Yu J. Inflammation: a mechanism of depression? Neurosci Bull 2014; 30: 515 – 523. 5. Dowlati Y, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry [ Internet ] 2010; 67: 446 – 457.
P102 THE IMMUNE-PHENOTYPE OF SMALL PLAQUE
PSORIASIS Touraj Khosravi-Hafshejani 1, Mehran Ghoreishi 2, Cristian Vera Kellet 3, Magdalena Martinka 4, Jan Dutz 1
1
Department of Undergraduate Medical Program, Faculty of Medicine,
2
Department of Dermatology, and Skin Science and 4 Department of Pathology and Laboratory Medicine, University of British Columbia, 3 Department of Dermatology, Pontifical Catholic University of Chile
Introduction: Small plaque psoriasis( SPP) is a subtype of psoriasis first described by Griffiths et al( 2007). It resembles guttate psoriasis but lesions are larger, are chronic, and are not associated with streptococcal infection. We have observed SPP develop in four different population groups; patients under TNFα-inhibitor therapy, patients under immune checkpoint inhibitor( ICI) therapy, and patients with concurrent SLE or ANA positivity and psoriasis. Subtypes of psoriasis develop on a spectrum between autoimmune and auto-inflammatory responses and an interplay between three signalling pathways are involved in their distinct pathogenesis. Chronic plaque psoriasis lesions are on the autoimmune spectrum, dominated by a T-cell mediated TNFα / IL-23 / IL-17 / IL-22 axis. Pustular psoriasis is a neutrophilic infiltrative inflammatory skin disease resulting from dysregulation of the IL-36 / IL-1 axis. Lastly, TNFα-inhibitor( TNFi) induced lesions have a SPP morphology and demonstrate increased expression of LL37 by keratinocytes, activated plasmacytoid dendritic cells and upregulated type-1 interferons( IFN). These lesions express fewer epidermal CD8 T cells. Objectives: Our aim is to characterize the immune-phenotype of SPP in multiple clinical scenarios. We hypothesize that SPP develops as a result of increased expression of cytokines and antimicrobial peptides involved in the type-1 IFN pathway. Methods: Skin biopsies were obtained from three patients with www. medicaljournals. se / acta