پاسخ تنظیمی ایمنی مرتبط با التهاب پایدار: بیش‌بیان PD-L1 و شناسایی RNA ویروسی در اوتیت چرکی مزمن

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه میکروب‌شناسی، دانشکده پزشکی، دانشگاه بابل، حله، عراق.

2 استاد گوش و حلق و بینی و آلرژی، گروه جراحی، دانشکده پزشکی، دانشگاه بابل، حله، عراق.

10.22103/jab.2026.26516.1823

چکیده

هدف: اوتیت میانی چرکی مزمن (CSOM) یک بیماری التهابی مزمن گوش میانی است که با تشکیل بیوفیلم‌های میکروبی، تغییر در مکانیسم‌های ایمنی، تخریب اپی‌تلیوم و آسیب بافتی مشخص می‌شود. هدف از این مطالعه تعیین ارتباط بین بیان PD-L1 و مثبت بودن RNA ویروسی در بیماران مبتلا به CSOM و بررسی نقش بالقوه تحلیل نقاط وارسی ایمنی (immune checkpoint) در تداوم بیماری بود.
مواد و روش‌ها: در این مطالعه، پنجاه شرکت‌کننده مورد بررسی قرار گرفتند که شامل پنجاه بیمار مبتلا به CSOM و بیست‌وپنج فرد سالم به‌عنوان گروه کنترل بودند. از میان شرکت‌کنندگان، ۵۰ نفر بیمار مبتلا به CSOM مراجعه‌کننده به بخش گوش، حلق و بینی بیمارستان عمومی دیوانیه و ۵۰ نفر افراد ظاهراً سالم بدون آسیب‌شناسی گوش میانی بودند. بیماران در بازه سنی ۱۵ تا ۷۵ سال از هر دو جنس قرار داشتند و بر اساس معاینات بالینی و اتوسکوپیک تشخیص داده شدند. برای شناسایی ژنوم ویروسی شامل ویروس سنسیشیال تنفسی (ژن N به طول ۱۱۳ جفت‌باز)، رینوویروس (ژن UTR به طول ۲۱۸ جفت‌باز) و آدنوویروس (۳۱۰ جفت‌باز)، آزمون RT-PCR انجام شد. سطح PD-L1 با استفاده از آزمون ایمونوفلورسانس و به روش لجستیک چهارپارامتری (ELI) اندازه‌گیری گردید.
نتایج: غربالگری مولکولی RNA ویروسی به روش RT-PCR نشان داد که اغلب بیماران مبتلا به اوتیت میانی چرکی مزمن دارای یک یا چند نتیجه مثبت از نظر ویروسی بودند. PCR برای شناسایی RNA ویروس‌ها (SARS-CoV-2، رینوویروس و آدنوویروس) در ۴۰ نفر از ۵۰ بیمار (۸۰٪) انجام شد و متعاقب آن، در ۱۰ نفر (20%) RNAرینوویروس و در ۶ نفر (12%) RNA آدنوویروس شناسایی گردید. میانگین سطح سرمی PD-L1 در بیماران به‌طور معنی‌داری بالاتر از گروه کنترل بود (13/0 ± 242/0 در برابر 05/0 ± 01/1 نانوگرم/میلی‌لیتر؛ 26/5t = ؛ 0001/0P <). همچنین، همبستگی مثبت معنی‌داری بین افزایش PD-L1 و مثبت بودن RNA ویروسی مشاهده شد. بیان PD-L1 در بیمارانی که از نظر RNA ویروسی مثبت بودند (06/1 نانوگرم/میلی‌لیتر) به‌طور قابل‌توجهی بیشتر از بیمارانی بود که نتیجه منفی داشتند (58/0 نانوگرم/میلی‌لیتر).
نتیجه‌گیری: وجود RNA ویروسی و بیش‌بیان PD-L1 در بیماران مبتلا به CSOM بیانگر یک پاسخ ایمنی تطابقی نامتوازن است که منجر به مهار التهاب بیش‌ازحد و افزایش تحمل میکروبی می‌شود. این یافته‌ها نشان می‌دهد که مسیر PD-1/PD-L1 نقش مهمی در ماهیت مزمن اوتیت میانی ایفا می‌کند.

کلیدواژه‌ها


عنوان مقاله [English]

Immunoregulatory response associated with persistent inflammation overexpression of PD-L1 and viral RNA detection in chronic suppurative otitis

نویسندگان [English]

  • Mohammed A. K. Al-Saadi 1
  • Safa H. Alturaihy 2
  • Intidhar Naeem Kareem 1
1 Department of Microbiology, College of Medicine, University of Babylon, Hilla, Iraq.
2 Professor of Otolaryngology and Allergy, Department of Surgery, College of Medicine, University of Babylon, Hilla, Iraq.
چکیده [English]

Objective
Chronic suppurative otitis media (CSOM) is a chronic middle ear inflammatory disease characterized by microbial biofilms, alterations in immune mechanisms, epithelium and tissue destruction. To determine the relationship between PD-L1 expression and viral RNA positivity in patients with CSOM and the potential role of immune checkpoint analysis in terms of chronicity.
Materials and methods
There were fifty participants in this study, which included fifty patients with CSOM and twenty-five healthy controls. 50 of them were patients with CSOM attending the Otorhinolaryngology Department, Diwaniyah General Hospital, and 50 of them were apparently healthy controls without middle ear pathology. Patients were aged between 15 and 75 years of both sexes, and they were diagnosed according to clinical and otoscopic examination. RT-PCR was carried out for the detection of the viral genome of the Respiratory Syncytial Virus (N gene of 113 bp), Rhinovirus (UTR gene of 218 bp) and Adenovirus (310 bp). PD-L1 was measured by immunofluorescence assay with a 4-parameter logistic method (ELI).
Results
Molecular screening for viral RNA by RT-PCR showed that the majority of patients with chronic suppurative otitis media (CSOM) had one or more viral-positive screens. PCR for the detection of RNA from the viruses (SARS-CoV-2, Rhinovirus, and Adenovirus) was performed in 40/50 (80%) patients, and thereafter, 10/50 (20%) and 6/50 (12%) of the patients were found to be positive for the presence of RNA from Rhinovirus and Adenovirus, respectively. The mean serum PD-L1 level was significantly higher in patients compared with controls (0.242 ± 0.13 versus 1.01 ± 0.05 ng/ml; t = 5.26; P < 0.0001). A positive correlation was found to exist between PD-L1 elevation and viral RNA positivity. PD-L1 expression was remarkably increased in those patients who were positive for viral RNA (1.06 ng/mL) compared to those who were negative (0.58 ng/mL)
Conclusion
The presence of viral RNA and PD-L1 overexpression in CSOM patients suggests an adaptive imbalanced immune response, which results in the silencing of hyperinflammation and microbial tolerance. These results suggest a major contribution of the PD-1/PD-L1 pathway to the chronic nature of otitis media.

کلیدواژه‌ها [English]

  • Corona Virus
  • Rhinovirus
  • Chronic Suppurative Otitis Media
  • Immune Checkpoint
  • RT-PCR
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