Sbarra Settimia, Vola Ambra, Tamarozzi Francesca, Najafi-Fard Saeid, Ludovisi Alessandra, Teggi Antonella, Nicastri Emanuele, Albarello Fabrizio, Brunetti Enrico, Goletti Delia, Petrone Linda
Translational Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, 00149 Rome, Italy.
Microbiology and Virology Unit, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy.
Infect Dis Rep. 2025 May 7;17(3):51. doi: 10.3390/idr17030051.
The identification of parasite- and stage-specific antigens is crucial for the development of new diagnostic tests for cystic echinococcosis (CE). We previously analysed the interleukin (IL)-4 response to T-specific peptides corresponding to the immunogenic regions of the five antigen B (AgB) subunits, demonstrating that AgB1 is the most immunogenic protein and that the response to all AgB peptides is associated with viable cysts. However, the response in patients with CE3a (WHO-IWGE) cystic stage was not evaluated and no other immunological factors besides IL-4 were included in the analysis. Four study groups were defined: "CE3a group" (transitional cysts), "CE3b group" (active cysts), "CE4/CE5 group" (inactive cysts), and "NO CE-group" encompassing patients with non-CE cysts (controls). Whole blood was stimulated in vitro with the five different T-specific peptide pools corresponding to the five AgB subunits and with a pool containing all five peptides' pools (total pool). IL-4 and other immunological markers were evaluated by ELISA and a multiplex assay, respectively. Twenty-four patients with CE (CE3a-group n = 3; CE3b-group n = 6; CE4/CE5-group n = 15) and 14 subjects with non-CE cysts were enrolled. IL-4 levels in response to AgB1 and AgB3 pools were significantly increased in CE compared to NO CE groups ( = 0.0201, = 0.0041). Within the CE patients, the highest IL-4 median level was observed in response to the AgB total pool, the AgB3 and AgB4 pools, followed by the AgB1 pool. Moreover, the IL-4 levels in response to the AgB1 pool were found to be significantly higher in the CE3b group compared to the CE4/CE5 group ( = 0.0070), while no differences were found for the CE3a group. As for other cytokines, we found higher IL-7 levels in response to the AgB4 pool in the CE4/CE5 group compared to the CE3b group ( = 0.0012), higher IL-2 levels in response to the AgB1 pool and AgB total pool in CE3b patients compared to controls ( = 0.0016), and higher IL-13 levels in response to the AgB total pool in patients with CE3b and CE4/CE5 cysts compared to NO CE ( = 0.0016; = 0.0009). These results contribute to a better knowledge of the immune interplay in the presence of CE and may be useful for further exploring the use of recombinant proteins/peptides in cytokine release assays for the diagnosis and follow-up of CE.
鉴定寄生虫和阶段特异性抗原对于开发新的囊型包虫病（CE）诊断测试至关重要。我们之前分析了白细胞介素（IL）-4对与五个抗原B（AgB）亚基免疫原性区域相对应的T特异性肽的反应，证明AgB1是最具免疫原性的蛋白质，并且对所有AgB肽的反应都与活囊肿相关。然而，未评估CE3a（WHO-IWGE）囊性阶段患者的反应，并且分析中未纳入除IL-4之外的其他免疫因素。定义了四个研究组：“CE3a组”（过渡性囊肿）、“CE3b组”（活动性囊肿）、“CE4/CE5组”（非活动性囊肿）以及“非CE组”，包括患有非CE囊肿的患者（对照）。用与五个AgB亚基相对应的五个不同T特异性肽库以及包含所有五个肽库的一个库（总库）在体外刺激全血。分别通过酶联免疫吸附测定（ELISA）和多重测定评估IL-4和其他免疫标志物。招募了24例CE患者（CE3a组n = 3；CE3b组n = 6；CE4/CE5组n = 15）和14例患有非CE囊肿的受试者。与非CE组相比，CE患者对AgB1和AgB3库反应的IL-4水平显著升高（P = 0.0201，P = 0.0041）。在CE患者中，观察到对AgB总库、AgB3和AgB4库反应的IL-4中位数水平最高，其次是AgB1库。此外，发现CE3b组对AgB1库反应的IL-4水平显著高于CE4/CE5组（P = 0.0070），而CE3a组未发现差异。至于其他细胞因子，我们发现CE4/CE5组对AgB4库反应的IL-7水平高于CE3b组（P = 0.0012），CE3b患者对AgB1库和AgB总库反应获得的IL-2水平高于对照组（P = 0.0016），并且CE3b和CE4/CE5囊肿患者对AgB总库反应的IL-13水平高于非CE组（P = 0.0016；P = 0.0009）。这些结果有助于更好地了解存在CE时的免疫相互作用，并且可能有助于进一步探索重组蛋白/肽在细胞因子释放测定中用于CE诊断和随访的用途。
