Bouazzaoui Abdellatif, Bogari Neda M, Al-Allaf Faisal A, Ekram Samar N, Athar Mohammad, Dannoun Anas, Schubert Thomas, Syed Shahzad N, Youssef Abdel-Rahman, Alqahtani Mashael, Abdellatif Ahmed A H
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
Science and Technology Unit, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
Heliyon. 2023 Feb 21;9(3):e13876. doi: 10.1016/j.heliyon.2023.e13876. eCollection 2023 Mar.
Graft versus host disease (GVHD) remains the major cause of morbidity and mortality after allogeneic stem cell transplantation, especially for intestinal GVHD, as steroid resistant GVHD results in high mortality. For this reason, new treatments of GVHD are needed. One approach is the reduction of pathogenic bacteria using anti- Immunoglobulin Yolk (IgY). In a haploidentical murine model, B6D2F1 mice conditioned with total body irradiation (TBI), received bone marrow cells (BM) and splenocytes (SC) from either syngeneic (Syn = B6D2F1) or allogeneic (Allo = C57BL/6) donors. Following this, animals received from day -2 until day +28 chow contained IgY or control chow. Thereafter the incidence and severity of aGVHD, the cytokines, chemokines, IDO1 and different pathogen-recognition receptors (PRR) were analyzed and compared to control animals (received chow without IgY). We found that animals receiving chow with IgY antibody showed reduced GVHD severity compared to control animals. On day28 after alloBMT, IDO, NOD2, TLR2, TLR4 and the inflammatory chemokine CCL3, were reduced in the colon and correlated with a significant decrease in bacteria. In summary chow containing chicken antibodies (IgY) improved GVHD via decrease in bacterial load of E coli conducting to reduction of pathogen receptors (NOD2, TLR2 and 4), IDO, chemokines and cytokines.
移植物抗宿主病（GVHD）仍然是异基因干细胞移植后发病和死亡的主要原因，尤其是肠道GVHD，因为类固醇抵抗性GVHD会导致高死亡率。因此，需要新的GVHD治疗方法。一种方法是使用抗免疫球蛋白蛋黄（IgY）减少病原菌。在一个单倍体小鼠模型中，用全身照射（TBI）预处理的B6D2F1小鼠，接受来自同基因（Syn = B6D2F1）或异基因（Allo = C57BL/6）供体的骨髓细胞（BM）和脾细胞（SC）。此后，从第-2天到第28天，动物接受含有IgY的食物或对照食物。然后分析急性移植物抗宿主病（aGVHD）的发病率和严重程度、细胞因子、趋化因子、吲哚胺2,3-双加氧酶1（IDO1）和不同的病原体识别受体（PRR），并与对照动物（接受不含IgY的食物）进行比较。我们发现，与对照动物相比，接受含IgY抗体食物的动物GVHD严重程度降低。在异基因骨髓移植后第28天，结肠中的IDO、核苷酸结合寡聚化结构域蛋白2（NOD2）、Toll样受体2（TLR2）、Toll样受体4（TLR4）和炎性趋化因子CCL3减少，并且与细菌的显著减少相关。总之，含有鸡抗体（IgY）的食物通过降低大肠杆菌的细菌载量改善了GVHD，从而导致病原体受体（NOD2、TLR2和4）、IDO、趋化因子和细胞因子的减少。
