# Accelerated involution of germinal center in palatine tonsils in IgA nephropathy

**Authors:** Hiroyuki Ueda, Kensuke Joh, Yoshimi Ueda, Hirokazu Marumoto, Masahiro Okabe, Nao Isaka, Nobuo Tsuboi, Hiromi Kojima, Yoichi Miyazaki, Takashi Yokoo

PMC · DOI: 10.1371/journal.pone.0301853 · PLOS ONE · 2024-05-06

## TL;DR

This study shows that IgA nephropathy is linked to changes in tonsil immune structures, which may contribute to kidney disease progression.

## Contribution

The study reveals a novel correlation between accelerated germinal center involution in tonsils and kidney disease severity in IgA nephropathy.

## Key findings

- IgAN tonsils show significantly smaller lymphoid follicles and germinal centers compared to controls.
- Reduced follicle area correlates with longer disease duration and higher proteinuria in IgAN patients.
- Smaller follicle area is linked to more severe kidney scarring in IgAN cases.

## Abstract

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.

## Linked entities

- **Diseases:** IgA nephropathy (MONDO:0005342)

## Full-text entities

- **Diseases:** urinary abnormalities (MESH:C536480), proteinuria (MESH:D011507), sclerosis (MESH:D012598), RT tonsils (MESH:D014069), IgA nephropathy (MESH:D005922)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC11073668/full.md

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Source: https://tomesphere.com/paper/PMC11073668