Nina Maria Hautala, Maija Joensuu, Teija Paakkola, Virpi Glumoff, Kaisa Kettunen, Janna Saarela, Mira Siiskonen, Zhi Chen, Katri Pylkäs, Timo Hautala
{"title":"Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin","authors":"Nina Maria Hautala, Maija Joensuu, Teija Paakkola, Virpi Glumoff, Kaisa Kettunen, Janna Saarela, Mira Siiskonen, Zhi Chen, Katri Pylkäs, Timo Hautala","doi":"10.1136/bmjophth-2024-001769","DOIUrl":null,"url":null,"abstract":"Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4 +CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"3 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Ophthalmology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/bmjophth-2024-001769","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4 +CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.
目的 眼弓形虫病(OT)可导致后葡萄膜炎,但复发性 OT 的病因尚不十分清楚。我们探讨了与复发性 OT 相关的临床、免疫学和遗传学特性。对临床病史、眼科检查结果和免疫学特性进行了评估。分析了B细胞和T细胞免疫分型,包括γ干扰素(IFN-γ)反应。对 592 个免疫缺陷基因进行了分析。首次发病的平均年龄为 23.8 岁(标准差 10.1 岁)。所有患者都有前葡萄膜炎、玻璃体炎和各种 OT 眼底病变。患者的淋巴细胞成熟异常;5/9 例患者的幼稚 CD4+CD45RA+CCR7+ T 细胞比例较高,7/9 例患者的 CD4+CD45RA-CCR7- T 效应记忆细胞比例降低。在 5/9 个病例中,观察到 CD19+CD38lowCD21low 活化 B 细胞的百分比增加。CD4+(8.45±4.17 vs 21.27±11.0,p=0.025)和CD8+(39.0±9.9 vs 18.1±18.1,p=0.017)T细胞的IFN-γ反应降低。遗传分析显示,在具有免疫活性的 ERCC3、MANBA、IRF4、HAVCR2、CARMIL2、CD247、MPO、C2 和 CD40 基因中存在几个潜在的有害变异。然而,我们研究的局限性包括未能确定统一的遗传机制。此外,我们也不能排除慢性弓形虫病引发免疫异常的可能性。尽管存在这些局限性,但我们的研究结果有助于理解眼部免疫和复发性 OT 的发展。