Publication: TNF-a bloker tedavisi başlanan romatoid artrit hastalarında tedavi öncesi ve tedavi sonrası multiplex laboratuvar yöntemi ile ölçülen sitokin ve kemokin düzeyleri ile klinik seyir ve tedavi yanıtı arasındaki ilişkinin değerlendirilmesi
Abstract
AMAÇ Romatoid Artrit (RA) etyolojisi net olarak bilinmeyen, daha çok sinoviyal eklemleri tutan ve eklem çevresinde progresif yıkım ile seyreden kronik, inflamatuar, sistemik, otoimmün bir hastalıktır. RA tanısında 1987 ACR ve 2010 yılında yayınlanan ACR/ EULAR tanı kriterleri kullanılmaktadır. Tüm dünyada, ortalama %1 ile en sık görülen inflamatuar artrittir. En sık 4. ve 5. dekatlarda olmakla beraber kadınlarda 23 kat daha fazla görülür. Hastalığın etyolojisi kesin olarak bilinmemekle birlikte genetik ve çevresel risk faktörleri suçlanmaktadır. RA patogenezinde sinovyum çevresinde ağırlıklı olarak mononükleer hücrelerin birikimi, birçok hücre tipi tarafından salınan sitokin ve kemokinlerin aracılığı ile bu hücrelerin sinovyuma akışı ve prolifere olmaları, sinovitis oluşumu, ardından eklemi oluşturan kemik ve kıkırdak dokuda aşınma ve erozyonlar söz konusudur. RA’nın karakteristik patolojisininin oluşmasında pro ve antiinflamatuvar sitokinler arasındaki dengenin bozulması önemli bir etkendir. Başta makrofaj kökenli IL-1 ve TNF-α olmak üzere, IL-6, IFN-γ, IL-12, IL-13, IL-15, IL-17, GM-CSF gibi bir çok proinflamatuvar sitokin ve MCP-1,IL-8 ve ENA-78 gibi proinflamatuvar kemokin hastalığın patogenezinde önemli rol almaktadırlar. RA’da laboratuvar bulguları nonspesifiktir. Klinik belirti ve bulgulara göre konulan tanıyı desteklemede veya hastalığın seyrini değerlendirmede kullanılabilir. Bu amaçla kullanılan RF, antiCCP antikorları ve serum CRP, ESR değerleri tanı ve hastalık aktivitesinde bilgiler vermektedirler ancak yapılan çalışmalarda çoğu laboratuvar tetkiklerinin hastalığın tanısında, seyrinde ve prognoz belirteci olarak kullanımlarında duyarlılıklarının ve özgüllüklerinin yeterince yüksek olmadığı saptanmıştır. Bu nedenle hastalığın tanısında, seyrinde ve prognoz tahmininde bilgi verebilecek moleküller araştırılmaktadır. Bizim çalışmamızın amacını da bu düşünce oluşturmakta olup hastalığın patogenezinde bu kadar önemli yer tutan sitokin ve kemokinlerden belirlediğimiz 9 adet sitokin (IL-1β, IL-1ra, IL-6, IL-10, IL-12, IL-13, TNF-α, VEGF, IFN-γ ) ve 1 adet kemokin (MCP-1) multiplex laboratuvar yöntemi ile ölçülmüş ve TNF-α bloker tedavisi öncesinde ve tedavi sonrasında 3. ve 6. aylarda ölçülen değerler ile hastalığın seyri arasında ilişkiler kurulmaya çalışılmıştır. Anahtar Sözcükler: Romatoid Artrit, TNF-α bloker tedavisi, sitokinler, kemokinler, multiplex, DAS28, hastalık aktivitesi.
OBJECTIVES Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic, autoimmune disease that primarily affects the synovial joints and causes progressif destruction around the joint. The diagnosis of RA can be made based on the 1987 ACR and 2010 ACR/ EULAR diagnostic criteria. %1 of world’s population is diagnosed with RA and thus it is the most common inflammatory arthritis. RA is 2-3 times more common in females than in males and it is most frequent in 4th-5th decades. The ethiology of the disease is unknown but there are several genetic and environmental risc factors that have been speculated. The pathophysiological chain of events starts with predominantly mononuclear cell clusters around the synovium, this is followed by the secretion of certain cytokines and chemokines from several cell types. These different types of cells migrate towards the synovium and proliferate causing a synovitis, followed by the abration and erosion of the bone and cartilage structure. The disturbance of the balance between the pro and anti-inflammatory cytonkines plays an important role in the typical pathological progress of RA. Abnormal production of certain proinflammatory cytokines (IL-6, IFN-γ, IL-12, IL-13, IL-15, IL-17, GM-CSF) and proinflammatory chemokines (MCP-1,IL-8 ve ENA-78 ) takes part in the inflammatory process and among all these factors macrophage originated IL-1 and TNF-α are known to play the most crucial role. The laboratory findings are non-specific in RA and they are rather used to support the diagnosis made by the clinical symptoms and findings and to assess the progress of the disease. RF, antiCCP antibodies and serum CRP and sedimentation rates can be usefull in confirming the diagnosis and assessing the progress of the disease, never-the-less several studies have showed that most of the laboratory findings are not sensitive or spesific enough in determining the diagnosis, progress or the prognosis of the disease. Therefore different molecules that can provide usefull information about the diagnosis,the progress and the prognoses of the disease have been sought. We have based our study on this idea and chose 9 cytokines (IL-1β, IL-1ra, IL-6, IL-10, IL-12, IL-13, TNF-α, VEGF, IFN-γ ) and 1 chemokine (MCP-1) to evaluate using a multiplex laboratory technique, we then tried to establish a relationship between the progress of the disease and the levels of these molecules before and 3-6 months after the TNF-α blocker treatment. Key Words: Rheumatoid Arthritis, TNF-α blocker treatment, cytokines, chemokines, multiplex, DAS28, disease activity
OBJECTIVES Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic, autoimmune disease that primarily affects the synovial joints and causes progressif destruction around the joint. The diagnosis of RA can be made based on the 1987 ACR and 2010 ACR/ EULAR diagnostic criteria. %1 of world’s population is diagnosed with RA and thus it is the most common inflammatory arthritis. RA is 2-3 times more common in females than in males and it is most frequent in 4th-5th decades. The ethiology of the disease is unknown but there are several genetic and environmental risc factors that have been speculated. The pathophysiological chain of events starts with predominantly mononuclear cell clusters around the synovium, this is followed by the secretion of certain cytokines and chemokines from several cell types. These different types of cells migrate towards the synovium and proliferate causing a synovitis, followed by the abration and erosion of the bone and cartilage structure. The disturbance of the balance between the pro and anti-inflammatory cytonkines plays an important role in the typical pathological progress of RA. Abnormal production of certain proinflammatory cytokines (IL-6, IFN-γ, IL-12, IL-13, IL-15, IL-17, GM-CSF) and proinflammatory chemokines (MCP-1,IL-8 ve ENA-78 ) takes part in the inflammatory process and among all these factors macrophage originated IL-1 and TNF-α are known to play the most crucial role. The laboratory findings are non-specific in RA and they are rather used to support the diagnosis made by the clinical symptoms and findings and to assess the progress of the disease. RF, antiCCP antibodies and serum CRP and sedimentation rates can be usefull in confirming the diagnosis and assessing the progress of the disease, never-the-less several studies have showed that most of the laboratory findings are not sensitive or spesific enough in determining the diagnosis, progress or the prognosis of the disease. Therefore different molecules that can provide usefull information about the diagnosis,the progress and the prognoses of the disease have been sought. We have based our study on this idea and chose 9 cytokines (IL-1β, IL-1ra, IL-6, IL-10, IL-12, IL-13, TNF-α, VEGF, IFN-γ ) and 1 chemokine (MCP-1) to evaluate using a multiplex laboratory technique, we then tried to establish a relationship between the progress of the disease and the levels of these molecules before and 3-6 months after the TNF-α blocker treatment. Key Words: Rheumatoid Arthritis, TNF-α blocker treatment, cytokines, chemokines, multiplex, DAS28, disease activity