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Immunohistological study in sixteen children with acute tubulointerstitial nephritis
Y Kobayashi1, M Honda, N Yoshikawa
1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Insights
Cellular immunity, particularly T lymphocytes, appears to be involved in the development of acute tubulointerstitial nephritis (ATIN) in children. Studies found increased T cell infiltration in ATIN kidneys compared to controls.
Area of Science:
- Pediatric Nephrology
- Immunology
- Cellular Biology
Background:
- Acute tubulointerstitial nephritis (ATIN) is a kidney disease with various causes, including drugs, infections, and autoimmune conditions.
- Understanding the immune cells involved in ATIN pathogenesis is crucial for developing targeted therapies.
- Previous studies have suggested a role for immune cells, but specific characterization in pediatric ATIN is limited.
Purpose of the Study:
- To characterize the types and numbers of interstitial mononuclear cells in pediatric patients with ATIN.
- To compare immune cell infiltration in ATIN kidneys with control kidney tissue.
- To explore potential correlations between specific immune cell populations and clinical subtypes of ATIN.
Main Methods:
- Enzyme immunoassay was performed on renal biopsy specimens from 16 children with ATIN and 6 control children.
- Immunohistochemistry was used to quantify CD3, CD4, and CD8 T lymphocytes, as well as monocytes/macrophages in the renal interstitium.
- Statistical analysis was employed to compare cell counts between groups and identify correlations.
Main Results:
- Children with ATIN showed significantly higher numbers of interstitial CD3, CD4, and CD8 T lymphocytes compared to controls.
- A positive correlation was observed between CD3 and CD4 T cells, and between CD3 T cells and monocytes/macrophages.
- The ratio of CD8 to CD3 T cells was notably low in some infection-induced ATIN cases, suggesting distinct immune responses.
Conclusions:
- Cellular immunity, predominantly mediated by T lymphocytes, likely plays a significant role in the pathogenesis of pediatric ATIN.
- The findings support the involvement of T cell-mediated immune responses in the development of ATIN across different clinical presentations.
- Further research into specific T cell subsets and their interactions may elucidate precise mechanisms and therapeutic targets.
Abstract:
Sixteen children (7 boys and 9 girls, aged 1.9 to 14.8 years) diagnosed with acute tubulointerstitial nephritis [ATIN: 4 drug-induced, 6 infection, 2 tubulointerstitial nephritis and uveitis syndrome (TINU), and 4 unclassified] were studied to characterize the nature of the interstitial mononuclear cells involved in each clinical picture of the disease Six children with asymptomatic microscopic hematuria whose histology was a minimal change in renal biopsy were studied as controls. The enzyme immunoassay was carried out using the biopsy specimen obtained from 4 to 42 days after the onset of illness. In ATIN, the number of renal interstitial infiltrating CD3, CD4, and CD8 T lymphocytes, respectively, was significant larger than that in the minimal change kidneys [CD3 T cells; median 94 (range 3.2-330)/mm2 interstitial area vs. median 7.8 (range 1.1-23), p = 0.003, CD4 T cells; 11 (range 0.5-78) vs. 1.5 (range 0-7.7), p = 0.018, CD8 T cells; 22 (range 1.0-150) vs. 2.9 (range 0-14), p = 0.047]. In addition, a positive correlation was found between the CD3 and CD4 T cells. On the other hand, in regard to the relationship between the CD3 and CD8 T cells, CD8/CD3 was extremely low in 3 cases in the infection-induced group, but the other 3 groups included no extremely low CD8/CD3 cases. Although interstitial monocytes/macrophages were smaller than the T lymphocytes in number, a positive correlation was revealed between the T lymphocytes and monocytes/macrophages (CD3 T cells vs. monocytes/macrophages; r = 0.53, p = 0.039). No relationship was found between the duration from the onset of illness to renal biopsy and mononuclear cell involvement. These findings suggest that cellular immunity, mainly T lymphocytes, may play a role in the pathogenesis of ATIN in children.