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Background <p>Tuberculosis (TB), caused by the <i>Mycobacterium tuberculosis</i> complex (MTBC), remains a major global health concern. It manifests as pulmonary TB and extrapulmonary TB (EPTB), with the latter including TB lymphadenitis (TBLN) and endometrial TB (ETB). While TBLN is the most common form, ETB is among the least studied despite its serious clinical consequences, such as infertility. Owing to its asymptomatic nature, ETB is often diagnosed at a late stage after irreversible tissue damage has occurred. The immune response in TB varies by infection site, yet very little is known about the local immune response at the infection site of the ETB. Cytokines such as TNF-α, IFN-γ, and TGF-β play critical roles in TB immunity, but their expression patterns differ across infection sites. Limited data exist on site-specific cytokine responses in the ETB and TBLN, making it essential to investigate immune markers in these forms of TB. This study examines cytokine expression and T-cell surface markers in formalin-fixed, paraffin-embedded (FFPE) biopsy samples to provide insights into immune dynamics and potential biomarkers for EPTB diagnosis.</p> Methods <p>A retrospective cross-sectional study was conducted using formalin-fixed, paraffin-embedded (FFPE) biopsy samples from ETB patients, TBLN patients, and controls. Immunohistochemistry (IHC) was performed to assess the expression of IFN-γ, TNF-α, and TGF-β, as well as CD4 + and CD8 + T-cell markers. Cytokine expression levels were quantified via QuPath softwares, and statistical comparisons were made via the Mann‒Whitney U test and the Kruskal‒Wallis test.</p> Results <p>Compared with controls, both ETB patients and TBLN patients presented significantly elevated IFN-γ and TNF-α expression (<i>p</i> &lt; 0.05). However, TGF-β expression was notably greater in the ETB than in the TBLN (<i>p</i> &lt; 0.05), suggesting a distinct immunoregulatory environment in the endometrium. CD4 + T-cell infiltration was significantly greater in the TBLN, whereas CD8 + T-cell presence was more pronounced in the ETB, indicating site-specific immune responses.</p> Conclusions <p>This study highlights distinct cytokine expression patterns in patients with endometrial tuberculosis (ETB) and tuberculosis lymphadenitis (TBLN). The differential cytokine expression in the ETB may be influenced by the unique immune microenvironment of endometrial tissue. These site-specific immune responses could contribute to variations in disease presentation and progression. The differential expression of TGF-β in the ETB suggests a potential role in immune modulation and fibrosis, which may contribute to tissue remodeling and reproductive dysfunction. Additionally, the increased levels of IFN-γ and TNF-α in both EPTB forms reinforce the involvement of localized immune responses in disease pathogenesis. Identifying these cytokine patterns may help uncover potential biomarkers for early diagnosis, which, upon validation through further studies, could enhance the detection and management of ETB.</p>

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Analysis of immune cytokines and cell surface markers in FFPE biopsy samples from patients with suspected endometrial and lymph Node Tuberculosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Negash Baye,
  • Abay Atnafu,
  • Selfu Girma,
  • Bethelehem Nigussie,
  • Yerega Belete,
  • Tigist Girma,
  • Sofia Yimam,
  • Kidist Bobosha,
  • Zewiditu Chanyalew,
  • Addisu Gize,
  • Menberework Chanyalew

摘要

Background

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), remains a major global health concern. It manifests as pulmonary TB and extrapulmonary TB (EPTB), with the latter including TB lymphadenitis (TBLN) and endometrial TB (ETB). While TBLN is the most common form, ETB is among the least studied despite its serious clinical consequences, such as infertility. Owing to its asymptomatic nature, ETB is often diagnosed at a late stage after irreversible tissue damage has occurred. The immune response in TB varies by infection site, yet very little is known about the local immune response at the infection site of the ETB. Cytokines such as TNF-α, IFN-γ, and TGF-β play critical roles in TB immunity, but their expression patterns differ across infection sites. Limited data exist on site-specific cytokine responses in the ETB and TBLN, making it essential to investigate immune markers in these forms of TB. This study examines cytokine expression and T-cell surface markers in formalin-fixed, paraffin-embedded (FFPE) biopsy samples to provide insights into immune dynamics and potential biomarkers for EPTB diagnosis.

Methods

A retrospective cross-sectional study was conducted using formalin-fixed, paraffin-embedded (FFPE) biopsy samples from ETB patients, TBLN patients, and controls. Immunohistochemistry (IHC) was performed to assess the expression of IFN-γ, TNF-α, and TGF-β, as well as CD4 + and CD8 + T-cell markers. Cytokine expression levels were quantified via QuPath softwares, and statistical comparisons were made via the Mann‒Whitney U test and the Kruskal‒Wallis test.

Results

Compared with controls, both ETB patients and TBLN patients presented significantly elevated IFN-γ and TNF-α expression (p < 0.05). However, TGF-β expression was notably greater in the ETB than in the TBLN (p < 0.05), suggesting a distinct immunoregulatory environment in the endometrium. CD4 + T-cell infiltration was significantly greater in the TBLN, whereas CD8 + T-cell presence was more pronounced in the ETB, indicating site-specific immune responses.

Conclusions

This study highlights distinct cytokine expression patterns in patients with endometrial tuberculosis (ETB) and tuberculosis lymphadenitis (TBLN). The differential cytokine expression in the ETB may be influenced by the unique immune microenvironment of endometrial tissue. These site-specific immune responses could contribute to variations in disease presentation and progression. The differential expression of TGF-β in the ETB suggests a potential role in immune modulation and fibrosis, which may contribute to tissue remodeling and reproductive dysfunction. Additionally, the increased levels of IFN-γ and TNF-α in both EPTB forms reinforce the involvement of localized immune responses in disease pathogenesis. Identifying these cytokine patterns may help uncover potential biomarkers for early diagnosis, which, upon validation through further studies, could enhance the detection and management of ETB.