Department of Internal Medicine, Division of Nephrology and Hypertension, The Jikei University School of Medicine, Tokyo, Japan.
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
PLoS One. 2024 May 6;19(5):e0301853. doi: 10.1371/journal.pone.0301853. eCollection 2024.
Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN.
The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated.
In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis.
The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.
腭扁桃体免疫反应的改变可能与 IgA 肾病（IgAN）的发病机制有关。生发中心是腭扁桃体中抗原特异性体液免疫反应的发生部位。IgAN（IgAN 扁桃体）的腭扁桃体中常观察到生发中心萎缩。然而，这些特征性变化的致病意义尚不清楚。本研究旨在探讨 IgAN 扁桃体次级淋巴滤泡的形态学变化，并评估形态计量学结果与 IgAN 临床病理严重程度的相关性。
采用年龄匹配的复发性扁桃体炎（RT 扁桃体）患者的扁桃体作为对照。评估淋巴滤泡萎缩程度与临床或肾活检组织病理学严重程度的相关性。
共纳入 87 例 IgAN 患者（48%为男性，中位年龄 35 岁，中位估算肾小球滤过率：74 mL/min/1.73 m2）。与 RT 扁桃体相比，IgAN 扁桃体的淋巴滤泡和生发中心的中位数较小（P < 0.001）。IgAN 扁桃体的总扁桃体组织中淋巴滤泡的相对面积（%LFA）和生发中心的相对面积（%GCA）明显小于 RT 扁桃体（P < 0.001）。然而，两组总扁桃体组织中边缘带的中位数比例相当。%LFA 与从尿异常出现到活检诊断的时间延长和尿蛋白排泄量增加呈负相关（P = 0.01）。%LFA 与肾小球的全球和节段性硬化的频率呈显著负相关。
本研究证实 IgAN 患者扁桃体生发中心的萎缩加速。IgAN 扁桃体的这种特征性变化与大量蛋白尿和肾脏的晚期慢性组织病理学变化相关，提示 IgAN 进展过程中反复发生的扁桃体免疫反应的参与。
