Langerhans Hücreli Histiositozda Prognostik Önemi Olan Faktörlerin Düzenleyici T Hücreleri ile İlişkisi

Abstract

Amaç: Langerhans hücreli histiositoz (LHH), dentritik hücrelerin anormal proliferasyonu ile karakterize klonal bir hastalık olup, yoğun inflamatuar bir mikroçevreye (TM) sahiptir. TM’nin, nadir görülen bu hastalığa olan katkısı hakkında bilgiler sınırlıdır. Bu çalışmada, TM deki regülatuar T hücreleri ve BRAFV600E mutasyonunu prognostik veriler ile karşılaştırmayı amaçladık. Gereç ve Yöntemler: Çalışmaya 26 olgu dahil edildi. Olguların yaş, cinsiyet, lokalizasyon, tekli-çoklu lokalizasyon, riskli organ tutulumu ve nüks durumlarına göre immünohistokimyasal olarak FOXP3+ regülatuar T hücre (Treg) sayısı ve BRAFV600E mutasyon varlığı değerlendirildi. Bulgular: Çalışmada yetişkin olgu sayısı çocuk sayısından daha fazla idi. En sık lokalizasyon kemik olup, olguların %81’i tek lokalizasyonlu idi. Riskli organ tutulumu ise 3 olguda mevcut olup, bunlardan ikisinde nüks görüldü. FOXP3+ Treg hücrelerinin sayısı; yetişkinlerde, tek lokalizasyon tutulumu olanlarda ve kemik tutulumu olanlarda yüksek olarak bulundu. Ayrıca nüks olan grupta FOXP3+ hücre sayısı nüks olmayan gruba göre daha yüksekti. BRAF V600E mutasyonu çocuklarda yetişkinlere oranla daha yüksekti (p=0.003), fakat prognostik parametreler ile karşılaştırıldığında istatiksel olarak anlamlı sonuç bulunamadı (p>0.05). Sonuç: BRAFV600E mutasyon varlığı çocuk hastalarda daha sık olmakla birlikte yetişkin hastalarda da görülmektedir. FOXP3+ Treg sayısı CD3+ ve CD4+ T hücre sayıları ile orantılıdır. TM de yer alan farklı oranlara sahip T hücreleri LHH patogenezinde önemli yere sahiptir

Keywords

• Langerhans,
• histiositoz,
• düzenleyici,
• FOXP3,
• BRAF,
• mutasyon

The Relationship of Prognostic Factors with Regulatory T Cells in Langerhans Cell Histiocytosis

Abstract

Aim: Langerhans cell histiocytosis (LCH), is a clonal disorder characterized by abnormal proliferation of dendritic cells, which has an intense inflammatory microenvironment. There is limited information about contribution of microenvironment to this rare disease. We aimed to compare regulatory T cells in microenvironment and BRAFV600E mutation with prognostic data. Material and Methods: Overall, 26 cases were included to the study. The number FOXP3+ regulatory T cell (Treg) and presence of BRAFV600E mutation were assessed according to age, gender, localization, unifocal or multifocal, involvement of organ at risk, and recurrence status in a histochemical manner. Results: The number of adult cases was higher than pediatric cases. Bone was the most common localization, and 81% of cases were unifocal. Risk organ involvement was observed in 3 cases, 2 of which showed recurrence. It was found that the number of FOXP3+ Tregs was higher in adults, those with unifocal localization, and those with bone involvement. In addition, the number of FOXP3+ Tregs was higher in the group with recurrence than those without recurrence. BRAFV600E mutation was higher in children when compared to adults (p=0.003), but, no significant correlation was found when compared with remaining prognostic parameters (p>0.05). Conclusion: Although BRAFV600E mutation is more common in pediatric patients, it can also be seen in adult patients. The number of FOXP3+ Tregs is proportional to CD3+ and CD4+ cells. T cells, which present at varying rates in microenvironment, play an essential role in the pathogenesis of LCH.

Keywords

• Langerhans,
• histiocytosis,
• regulatory,
• FOXP3,
• BRAF,
• mutation

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