Comparative immuno‐profiling of proliferative and disordered proliferative endometrium in anovulatory abnormal uterine bleeding

Mishu Mangla, Seetu Palo, Poojitha Kalyani Kanikaram, P. Raja Shekar, Aparna Setty
In: Journal of Obstetrics and Gynaecology Research · 2025 · vol. 51(8) , pp. e70032 · doi:10.1111/jog.70032 · PMID:40760735 · W4412949176
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found no significant differences in CD4, CD8, CD56, or CD68 immune cell counts between proliferative and disordered proliferative endometrium in women with anovulatory abnormal uterine bleeding.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

This study compared immune cell profiles in endometrial biopsies from 73 women with anovulatory abnormal uterine bleeding (AUB), classifying tissue as proliferative versus disordered proliferative endometrium (DPE). Using immunohistochemistry, the authors quantified CD4+ helper T cells, CD8+ cytotoxic T cells, CD56+ natural killer cells, and CD68+ macrophages across high-power fields, and found no statistically significant differences in immune marker counts or several clinical parameters between the two histologic groups. Correlation analyses instead showed significant positive associations among immune markers (e.g., CD4 with CD8, CD8 with CD68, and CD4 with CD56), with CD56 negatively correlated with BMI and positively correlated with bleeding duration. The paper concludes that local immune infiltration may not substantially differ between proliferative and DPE, while noting that larger studies and functional immune profiling are needed to detect subtle differences. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

BACKGROUND: Anovulatory abnormal uterine bleeding (AUB) is frequently associated with prolonged unopposed estrogen exposure, resulting in histological patterns ranging from proliferative to disordered proliferative endometrium (DPE). While these entities are histologically distinguishable, their immunological microenvironments remain underexplored. OBJECTIVE: To compare the immune cell profile of proliferative and DPE in women with anovulatory AUB, focusing on key immune markers: CD4, CD8, CD56, and CD68. METHODS: wEndometrial biopsies from women diagnosed with anovulatory AUB were classified histologically as proliferative or disordered proliferative. Immunohistochemical staining was performed to quantify CD4+ helper T cells, CD8+ cytotoxic T cells, CD56+ natural killer cells, and CD64+ macrophages. Quantitative analysis was conducted using high-power field (hpf) counts, and statistical comparisons were made using appropriate non-parametric tests. RESULTS: A total of 73 women with AUB were analyzed, including 30 with proliferative and 43 with DPE. No statistically significant differences were observed between the two groups in age, body mass index (BMI), endometrial thickness, Pictorial Blood Assessment Chart score, or immune cell counts (CD4, CD8, CD68, CD56/hpf). Correlation analysis revealed significant positive associations among immune markers, particularly between CD4 and CD8 (r = 0.425, p < 0.001), CD8 and CD68 (r = 0.316, p = 0.006), and CD4 and CD56 (r = 0.377, p = 0.001). CD56+ cells also showed a negative correlation with BMI (r = -0.251, p = 0.032) and a positive correlation with duration of bleeding (r = 0.289, p = 0.013). CONCLUSION: The local immune cell infiltration may not differ substantially between proliferative and DPE in the context of AUB. No statistically significant differences were observed between the two groups with respect to clinical parameters, endometrial thickness, or immune cell marker expression (CD4, CD8, CD68, and CD56). Positive correlations between CD4, CD8, CD68, and CD56 cells suggest coordinated immune activity within the endometrial microenvironment. Further studies with larger sample sizes and functional immune profiling are warranted to explore subtle immunological variations that may influence endometrial physiology and pathology.
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Abstract

Background Anovulatory abnormal uterine bleeding (AUB) is frequently associated with prolonged unopposed estrogen exposure, resulting in histological patterns ranging from proliferative to disordered proliferative endometrium (DPE). While these entities are histologically distinguishable, their immunological microenvironments remain underexplored.

Objective

To compare the immune cell profile of proliferative and DPE in women with anovulatory AUB, focusing on key immune markers: CD4, CD8, CD56, and CD68.

Methods

wEndometrial biopsies from women diagnosed with anovulatory AUB were classified histologically as proliferative or disordered proliferative. Immunohistochemical staining was performed to quantify CD4+ helper T cells, CD8+ cytotoxic T cells, CD56+ natural killer cells, and CD64+ macrophages. Quantitative analysis was conducted using high-power field (hpf) counts, and statistical comparisons were made using appropriate non-parametric tests.

Results

A total of 73 women with AUB were analyzed, including 30 with proliferative and 43 with DPE. No statistically significant differences were observed between the two groups in age, body mass index (BMI), endometrial thickness, Pictorial Blood Assessment Chart score, or immune cell counts (CD4, CD8, CD68, CD56/hpf). Correlation analysis revealed significant positive associations among immune markers, particularly between CD4 and CD8 (r = 0.425, p < 0.001), CD8 and CD68 (r = 0.316, p = 0.006), and CD4 and CD56 (r = 0.377, p = 0.001). CD56+ cells also showed a negative correlation with BMI (r = −0.251, p = 0.032) and a positive correlation with duration of bleeding (r = 0.289, p = 0.013).

Conclusion

The local immune cell infiltration may not differ substantially between proliferative and DPE in the context of AUB. No statistically significant differences were observed between the two groups with respect to clinical parameters, endometrial thickness, or immune cell marker expression (CD4, CD8, CD68, and CD56). Positive correlations between CD4, CD8, CD68, and CD56 cells suggest coordinated immune activity within the endometrial microenvironment. Further studies with larger sample sizes and functional immune profiling are warranted to explore subtle immunological variations that may influence endometrial physiology and pathology. CONFLICT OF INTEREST STATEMENT Nil. DATA AVAILABILITY STATEMENT The data supporting the findings of this study have been included as Data S1.

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