Immune dysregulation in endometrial tuberculosis: elevated HLA-G and IL-1Ra as key modulators

Abstract

Endometrial tuberculosis (ETB) is a reproductive system infection caused by Mycobacterium tuberculosis, primarily invading the endometrium through hematogenous dissemination. This study included 10 patients diagnosed with ETB and 10 patients with pulmonary tuberculosis (PTB) to analyze their clinical, pathological, and immunological characteristics. Anatomically, PTB presented the highest prevalence among tuberculosis cases. Compared to PTB imaging, CT scans of ETB showed less distinctive diagnostic features. Pathologically, abscess formation was more frequently observed in ETB patients than in PTB patients, suggesting a more intense local inflammatory response in ETB. However, there were no statistically significant differences in granulomatous lesions, caseous necrosis, coagulative necrosis, inflammatory necrosis, exudation, acute inflammation, or fibrous tissue hyperplasia between the two groups. Immunohistochemical analysis revealed higher infiltration of macrophages (CD68) in ETB lesions compared to PTB, whereas the counts of T cells (CD3+, CD4+, CD8+) and B cells (CD20) showed no significant differences. Notably, the expression levels of HLA-G and IP-10 were significantly elevated in the lesion areas of ETB compared to PTB. Similarly, the expression of HLA-G, IP-10, IL-1Ra, and IL-10 was significantly higher in the ETB group than in the PTB group. Furthermore, HLA-G and IL-1Ra expression levels were markedly elevated in ETB lesion areas compared to surrounding normal endometrial tissue. HLA-G plays a pivotal role in immune tolerance by modulating local immune responses, while IP-10 is involved in chronic inflammatory signaling. IL-1Ra and IL-10 are key regulators of endometrial immune homeostasis, counterbalancing inflammatory responses that could otherwise disrupt reproductive function. These immunoregulatory factors are crucial in maintaining immune tolerance within the endometrium and may influence immune responses associated with endometrial tuberculosis.

Keywords: HLA-G; IL-1ra; endometrial tuberculosis; pathological characteristics; pulmonary tuberculosis; tuberculous granuloma.

Figure 1

The sequence of detection loci on the membrane strip. MTC: Mycobacterium tuberculosis complex; CC: quality control locus; all other loci represent non-tuberculous mycobacteria detection sites. (A) The positive Mycobacterium control. (B) The negative Mycobacterium control.

Figure 2

Illustrates imaging findings. (A) depicts nodular and patchy high-density shadows in the lungs, unevenly distributed and indicative of tuberculous lesions. (B) presents pelvic CT images in axial and sagittal planes, showing the uterus and surrounding structures.

Figure 3

Illustrates the pathological features observed in both groups. Chronic granulomatous inflammation with caseous necrosis is a hallmark pathological change in pulmonary tuberculosis (PTB) and endometrial tuberculosis (ETB). Hematoxylin and eosin (H&E) staining reveals coagulation necrosis,inflammatory necrosis, exudation, acute inflammation, and fibrous tissue proliferation. Acid-fast staining identifies the presence of Mycobacterium tuberculosis. Scale bar: 200 μm; magnification: H&E (200×).

Figure 4

Illustrates immune cell infiltration and statistical analysis among the three groups. Immune cells, including CD3+ T cells, CD4+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophages, were identified using immunohistochemical staining. (A) Comparison between the PTB group (P) and the ETB lesion group (F). (B) Comparison between the PTB group (P) and the overall ETB group (E). (C) Comparison between the ETB lesion group (F) and its surrounding tissues (S). Scale bar: 200 μm; magnification: immunohistochemical staining (200×).

Figure 5

Illustrates the infiltration and expression of inflammatory factors across three groups. Immunohistochemical staining was employed to visualize the infiltration of inflammatory factors. (A) Comparison between the PTB group and the ETB lesion group. (B) Comparison between the PTB group and the overall ETB group. (C) Comparison between the ETB lesion group and its surrounding tissues. (D) The PTB group. (E) The ETB lesion group. (F) The overall ETB group. (G) surrounding tissues. Scale bar: 200 μm; magnification: 200×, immunohistochemical staining.