Özet
İmmünoglobulin G4-ilişkili hastalık (IgG4-RD), tümefaktif organ tutulumu, IgG4-pozitif plazma hücrelerle zengin lenfoplazmasitik infiltrasyon, storiform fibrozis ve relapsing-remitting seyir ile karakterize sistemik fibro-enflamatuvar bir hastalıktır. Glukokortikoidler indüksiyon tedavisinin temel taşı olmakla birlikte, doz azaltılması sonrasında relaps oranları yüksek kalmakta ve uzun süreli steroid maruziyeti önemli morbiditeye neden olmaktadır. Artan kanıtlar, IgG4-RD’nin tek tip bir hastalık olmaktan ziyade, heterojen immün yolaklar tarafından yönlendirilen immunolojik olarak farklı endotipler spektrumu olduğunu göstermektedir. Bunlar tip 2 enflamatuvar aksı [interlökin-4 (IL-4)/IL-13-dominant], B-hücre ve plazmablast ekspansiyonu, T foliküler yardımcı hücre aktivasyonu, sitotoksik CD4+T-hücre yanıtları, kompleman-ilişkili mekanizmalar ve profibrotik makrofaj sinyallemesini içermektedir. Bu immün endotipler tanınması, fenotip-yönelimli terapi için mekanik bir çerçeve sağlamaktadır. B-hücre-hedefli terapiler (rituksimab ve yeni Amerikan Gıda ve İlaç Dairesi-onaylı inebilizumab) nükseden hastalıkta etkinlik göstermiş, oysa IL-4/IL-13 blokajı seçilmiş Th2-eğilimli hastalarda rasyonel bir strateji olabilmektedir. B-hücre aktive edici faktör sinyallemesi, Bruton tirozin kinaz yolakları ve fibrotik mekanizmaları hedef alan yaklaşımlar, hassas immünoterapiye doğru bir kayışı desteklemektedir. Bu derleme, IgG4-RD’deki immünolojik endotipler hakkında mevcut kanıtları sistematikleştirmekte ve immün imzaları terapötik stratejilere bağlayan kavramsal bir çerçeve sunmaktadır. Endotip-rehberli yönetim paradigması, bu heterojen hastalık spektrumunda kümülatif steroid maruziyetini azaltabilir ve nüks riskini düşürebilir.
Anahtar Kelimeler:
IgG4-ilişkili hastalık, immünolojik endotipler, klinik fenotipler, B-hücre terapisi, inebilizumab, terapötik stratifikasyon
Kaynaklar
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