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Son Gelişmeler Işığında Lupus Nefriti Patogenezi

Recent Developments in the Pathogenesis of Lupus Nephritis

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2014
DOI: 
10.5262/tndt.2014.1003.01

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a high incidence of renal involvement during its course contributing to disease morbidity and mortality. All compartments of the kidney may be affected by the disease but the term “lupus nephritis” is used to define glomerular pathology. There have been intensive studies to uncover the mechanisms underlying renal injury. Typically in SLE there are autoreactive B cells producing multiple autoantibodies that react with self antigens, and glomerular immune complexes are believed to be the primary mediators of renal disease. Cellular injury development at sites of immune complex deposition in the glomeruli is facilitated by both Fc receptor-mediated inflammation and direct cytotoxicity of the complement system. Deficiency of early classical complement pathway proteins that lead to defective clearance of apoptotic antigens is also linked to the etiopathogenesis. Among the various autoantibodies, the double-stranded anti- DNA (dsDNA) antibody subpopulation is considered to be nephritogenic. Recent studies have revealed that chromatin fragments are the key elements in the pathogenesis as extracellular dsDNA is found in the form of nucleosome in chromatin fragments. Non-immune pathogenetic mechanisms are also considered. Although there has been a significant progress in lupus nephritis management, advances in pathogenesis is still merging.
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Abstract (Original Language): 
Sistemik otoimmün bir hastalık olan Sistemik Lupus Eritematozus’da renal tutulum mortalite-morbidite riski olan ve sık görülen ciddi bir komplikasyondur. “Lupus nefriti” terimi primer olarak glomerüler hasarı ifade etmek için kullanılmaktadır. Araştırmalar glomerüler hasara neden olan patogenetik mekanizmalar üzerinde yoğunlaşmıştır ve temel olarak immün aracılı patogenetik mekanizmalar tanımlanmış, otoreaktif B lenfositlerin ürettiği antinükleer otoantikorlar patogenezden sorumlu tutulmuştur. Otoantikorların hedef antijenler ile bağlanarak immün kompleks oluşturması ve bu immün komplekslerin glomerüllerde depolanması renal tutulumun en erken belirtilerindendir. İmmünkompleks depolanmasını takiben Fc reseptör aracılı inflamasyon ve kompleman bağımlı direkt sitotoksisite doku hasarına neden olmaktadır. Lupus nefritinde erken klasik kompleman yolağı proteinleri ile ilgili kusurlar apopitotik cisimciklerin temizlenme kusuruna neden olmakta ve otoimmün CD8 T lenfositlerin sitotoksik etkisi ile artmış olan apopitotik kromatinin yetersiz temizlenmesi patogenezde önemli basamağı oluşturmaktadır. Anti nükleer antikorlardan özellikle anti double stranded DNA (dsDNA) subpopulasyonu nefritojenik olarak kabul edilmektedir ve son bilgiler ekstraselüler dsDNA’nın apopitoza giden hücrelerin ortama saldığı kromatin fragmanında nükleozom formunda bulunduğunu göstermiş, kromatin fragmanlarının patogenezde ana rolü oynadığını ortaya koymuştur. Non-immün patogenetik mekanizmalar arasında fokal segmental nekrotizan glomerüler patoloji ile seyreden “pauciimmune” nötrofil bağımlı vaskülitik mekanizmalar sorumlu tutulmaktadır. Renal prognoz ve tedavi ile ilgili ciddi gelişmeler elde edilmiş olmasına rağmen lupus nefriti patogenezi ile ilgili gelişmeler sınırlıdır.
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