Molecular alterations in the pathogenesis of two chronic dermatoses – vitiligo and psoriasis

Abstract

Vitiliigo on krooniline nahahaigus, mis väljendub valgete laikudena nahal. Vitiliigo mõjutab patsiendi elukvaliteeti, sest avaldub tihti lapse- ja noorukieas ning haiguskolded paigutuvad enamasti avatud kehapiirkondadesse. Puudulikud teadmised vitiliigo tekkemehhanismidest on takistanud tõhusate ravimeetodite väljatöötamist. Psoriaas on sage krooniline põletikuline haigus, mis väljendub punetavate ja ketendavate haiguskolletena nahal, millele võib kaasneda küünte ja liigeste kahjustus. Kuigi bioloogilise ravi kasutuselevõtt on psoriaasi ravitulemusi parandanud, ei toimi see kõigil haigetel võrdväärselt tõhusalt ning senini ei osata ravitulemust ega haiguse kulgu täielikult ette ennustada. Selleks, et hankida uut informatsiooni vitiliigo ja psoriaasi tekkemehhanismide kohta, kaasasime uuringusse 23 vitiliigot ja 43 psoriaasi põdevat patsienti ning 32 tervet vabatahtlikku. Määrasime uuritavate nahast ja verest immuunsüsteemi töös osalevate geenide ja valkude avaldumist. Lisaks uurisime vitiliigoga haigete nahas mikroRNAde avaldumist. MikroRNAd on väikesed, aga võimsad pärilikkusaine osakesed, mis mõjutavad geenide avaldumist ja seoses sellega kaudselt kõiki protsesse organismis. Kui varasemalt arvati, et nii vitiliigo kui ka psoriaas on peamiselt autoimmuunsed haigused, st. et häirunud on eeskätt omandatud immuunsus, siis meie uuringus ilmnes, et häirunud on ka mitmed etapid kaasasündinud immuunsuse töös. See on immuunsüsteemi osa, mis on pidevas valmisolekus, et kaitsta organismi väliskeskkonnast pärinevate ohtude eest. Teiseks leidsime, et vitiliigo korral on nii pigmendi- kui ka naharakkudes aktiveerunud protsess nimega autofaagia, mille käigus õgitakse ära rakkude vigased koostisosad. Kolmandaks tuvastasime, et vitiliigot põdevate patsientide nahas on muutunud paljude mikroRNAde, mis osalevad pigmenditootmises ja põletikuprotsessis, avaldumine. Kui viisime ühe nendest mikroRNAdest pigmendi- ja naharakkude sisse, muutus omakorda paljude põletikus ja pigmenditootmises osalevate geenide avaldumine. Antud uurimistöö tulemused näitavad, et tulevikus on tarvis lisauuringuid selgitamaks kaasasündinud immuunsüsteemi, autofaagia ja mikroRNAde rolli vitiliigo ja psoriaasi kulgu ennustavate markeritena, diagnostiliste markeritena ja ravi märklaudadena.

Vitiligo is a chronic skin disease that manifests as white spots on the skin. As the onset of vitiligo is often during childhood or adolescence and white spots mostly locate on visible body parts, vitiligo affects the quality of life. Lack of knowledge about the pathogenesis of vitiligo has impeded the development of effective methods of treatment. Psoriasis is a common chronic inflammatory disease that is characterized by red and scaly patches on the skin and often also by nail changes and joint inflammation. Biological therapy has improved the results of the treatment but the treatment is not always effective and to date we are unable to predict the results and the course of the disease. In order to obtain new information about the mechanisms of these diseases, we involved 23 patients with vitiligo, 43 patients with psoriasis and 32 healthy control individuals in the study. The expression of genes and proteins that participate in the immune system was measured in the skin and blood of the participants. Additionally, the expression of microRNAs was assessed in the skin of vitiligo patients. MicroRNAs are small but powerful parts of genetic information. They have a power to suppress the expression of genes and therefore to influence all the processes in the organism. Vitiligo and psoriasis are generally considered to be autoimmune disorders. It means that adaptive immunity is activated and attacks the body itself. However, we found that innate immunity is disturbed as well. Innate immunity is the part of immune system that normally is in constant state of readiness to attack. Secondly, we revealed that the process called autophagy is activated in the skin cells and pigment cells of vitiligo skin. Autophagy is a mechanism of the cell that removes unnecessary and dysfunctional components. Thirdly, the expression of many microRNAs that regulate immunity and pigmentation was disturbed in the skin of vitiligo patients. When we inserted one of these microRNAs into the skin cells and pigment cells, the expression of many immunity- and pigmentation-related genes changed as a result. The results of this study show that further studies are needed to specify the role of innate immunity components, autophagy and microRNAs as prognostic markers, diagnostic markers and treatment targets of vitiligo and psoriasis.