Zlacka Denisa, Sedlacek Petr, Prucha Miroslav, Hromadnikova Ilona
Cell Biology Laboratory, Department of Paediatrics, University Hospital Motol, Charles University, Prague, Czech Republic.
Pediatr Transplant. 2006 Nov;10(7):794-804. doi: 10.1111/j.1399-3046.2006.00566.x.
Allogeneic SCT remains the only means of cure for many patients with various malignant disorders as well as non-malignant diseases. Infection together with severe aGvHD may result in a significant incidence of transplant-related morbidity and mortality. Current evidence suggests that hSPS represent major immunodominant antigens in many pathogens and therefore might play an important role in the pathogenesis of GvHD. We investigated the levels of total Ig, IgG and IgM isotype antibodies to rh-hsp60, recombinant Mycobacterium bovis hsp65 and stress-inducible rh-hsp70 in sera of pediatric patients undergoing SCT by using ELISA. We studied whether humoral immune responses to hSPS follow transplant-related complications, bacterial and fungal infection. Anti-hsp antibodies were detected in patients' sera before conditioning, over the course of conditioning and all the time post-transplant. We found no correlation between anti-hsp antibodies and the occurrence and severity of GvHD and/or other transplant-related complications like graft failure, hemorrhagic cystitis and capillary leakage syndrome. However, elevated anti-hsp antibodies involving IgM and IgG isotypes were found to be associated with bacterial and fungal infection depending on etiological agents. We demonstrated de novo humoral response to hSPS in a cohort of patients with actual infection caused by Klebsiella pneumoniae (anti-hsp60, anti-hsp65 and anti-hsp70), Pseudomonas aeruginosa (anti-hsp60, anti-hsp70) and Aspergillus fumigatus (anti-hsp65). We conclude that anti-hsp antibodies might be produced after SCT in relation to infection depending on etiological agents; however, transplant-related complications by themselves had a little impact.
异基因造血干细胞移植(SCT)仍然是许多患有各种恶性疾病以及非恶性疾病患者的唯一治愈方法。感染与严重的急性移植物抗宿主病(aGvHD)可能导致移植相关的发病率和死亡率显著增加。目前的证据表明,热休克蛋白(hSPS)在许多病原体中代表主要的免疫显性抗原,因此可能在移植物抗宿主病(GvHD)的发病机制中起重要作用。我们使用酶联免疫吸附测定(ELISA)法,研究了接受SCT的儿科患者血清中针对重组人热休克蛋白60(rh-hsp6)、重组牛分枝杆菌热休克蛋白65(hsp65)和应激诱导型重组人热休克蛋白70(rh-hsp70)的总免疫球蛋白(Ig)、IgG和IgM同种型抗体水平。我们研究了针对hSPS的体液免疫反应是否与移植相关并发症、细菌和真菌感染有关。在预处理前、预处理过程中以及移植后的所有时间都在患者血清中检测到了抗热休克蛋白抗体。我们发现抗热休克蛋白抗体与GvHD的发生和严重程度以及/或其他移植相关并发症(如移植物衰竭、出血性膀胱炎和毛细血管渗漏综合征)之间没有相关性。然而,发现涉及IgM和IgG同种型的抗热休克蛋白抗体升高与取决于病原体的细菌和真菌感染有关。我们在一组由肺炎克雷伯菌(抗hsp60、抗hsp65和抗hsp70)、铜绿假单胞菌(抗hsp60、抗hsp70)和烟曲霉(抗hsp65)引起实际感染的患者中证明了对hSPS的从头体液反应。我们得出结论,SCT后可能会根据病原体产生与感染相关的抗热休克蛋白抗体;然而,移植相关并发症本身影响较小。