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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Improved diagnostic accuracy for pediatric obstructive sleep apnea using an out-of-center sleep test.

OBJECTIVE: Polysomnography (PSG) is considered the gold standard for diagnosing obstructive sleep apnea syndrome (OSA) in children. However, many hospitals do not carry out PSG evaluations, and use out-of-center sleep test (OCST) devices for diagnosis instead. The aim of this study was to confirm the reliability of OCSTs for the diagnosis of pediatric OSA. We also investigated the factors influencing diagnostic reliability of OCST for the severe OSA patients who should be treated earlier. METHODS: This was a retrospective study using the Ota Memorial Sleep Center database. We analyzed the data of children who underwent Type 4 OCST at home and Type 1 PSG in the sleep lab between April 2006 to April 2015. Cephalometric parameters and anthropometric findings such as enlarged tonsils were also evaluated. We compared the 3% oxygen desaturation index (ODI3%) measured by OCST with the apnea-hypopnea index (AHI) measured by PSG. We used Receiver Operator Curve (ROC) to calculate the optimal OCST- ODI3% value to diagnose PSG-AHI ≥10 per hour. In order to determine which factors increase the accuracy of OCST, we calculated the accuracy, sensitivity and specificity in regard to the predicted values using multiple logistic regression analysis. The Ethics Committee of Ota General Hospital approved the study (approval no. 21018). RESULTS: A total of 191 children were enrolled in this study. The study included 127 boys and 64 girls, with a mean age of 5.4 years (range: 3-8 years), BMI of 15.7 kg/m² (range: 11.5-35.7 kg/m²), PSG-AHI of 17.4 per hour (range: 0.3-89.8 per hour). The sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were 64.4%, 70.3% and 67.5%, respectively, to detect PSG-AHI ≥ 10 per hour for children with suspected OSA. Multivariable stepwise regression revealed that increases of sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were independently predicted by facial axis, which is cephalometric angle of 81° or less, and tonsil hypertrophy, which is Brodsky +3 or +4, showing increases to 73.3%, 71.3%, and 72.3%, respectively, whereas age, gender, body mass index, adenoid size and other cephalometric parameters were not significant predictors. CONCLUSION: The results of the statistical analyses suggest that it would be useful to add the assessment of tonsil size and facial axis as well as OCST to determine whether the threshold of PSG-AHI ≥ 10 per hour has been crossed.

Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation.

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.