PMC8113859_01
Clinical features of the patients with PIK3CD mutations. Patient 1 (A-C): CT scan reveals pulmonary nodules with cavity formation, and patchy infiltration (A, right lung), and maxillary sinusitis (B); Hematoxylin and eosin (HE) staining of renal biopsy showed no proliferation of capillary endothelial cells and mesangial cells in the glomeruli, no thickening of the basement membrane, and no glomerular sclerosis and interstitial fibrosis (C). Patient 2 (D-I): CT scan reveals pulmonary nodules with cavity formation, and patchy infiltration (D), and maxillary sinusitis (E); HE stains for renal biopsy showed minimal change, mild mesangial cell hyperplasia in glomerulus (F), similar to patient 1; Bronchoscopy shows mucosal nodule lymphoid hyperplasia from pharynx to the entire airway (G-I).
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CT also showed pulmonary nodules with cavity formation, and patchy infiltration, and bilateral maxillary sinus and ethmoid sinusitis ( Table 1 ,  Figures 1D, E ). Due to recurrent and refractory lung infections, she underwent bronchoscopy during hospitalization, showing mucosal nodule lymphoid hyperplasia in the entire airway ( Figures 1G-I ). Lung biopsy suggested inflammatory cells infiltration ( Figure 2 ) and absence of granulomatous lesions, and renal biopsy pathology indicated mild glomerular disease ( Figure 1F ).
Immunohistochemical analyses for p110delta, CD3, and CD20. Compared with control (A, D), expression of p110delta (brown signal) in lung tissue and lymph node sections from patient 1 (B, E) and 2 (C, F) significantly increased. Many inflammatory cells infiltrated around the airway and in the lung parenchyma (H, I, K, L). Relative to control (G, J), CD3+ T cells (H, I, brown signal) and CD20+ B cells (K, L, brown signal) significantly increased, especially CD3+ T cells. The control lung sample was from a child's lung tumor resection, and lymph node sample was from a child with reactive lymph node hyperplasia.
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Lung biopsy suggested inflammatory cells infiltration ( Figure 2 ) and absence of granulomatous lesions, and renal biopsy pathology indicated mild glomerular disease ( Figure 1F ). Immunohistochemical staining of p110delta, CD3, and CD20 were performed in biopsy tissues of both patients taken previously ( Figure 2 ). Increased expression of p110delta was found in histological sections of the lung and lymph node compared with the control, indicating increased recruitments of p110delta expressing cells ( Figures 2B, C, E, F ). T cells ( Figures 2H, I, K, L ). This study was approved by the Ethic Review Board of Children's Hospital, Zhejiang University School of Medicine (2019-IRB-105).
PMC8113859_02
Clinical features of the patients with PIK3CD mutations. Patient 1 (A-C): CT scan reveals pulmonary nodules with cavity formation, and patchy infiltration (A, right lung), and maxillary sinusitis (B); Hematoxylin and eosin (HE) staining of renal biopsy showed no proliferation of capillary endothelial cells and mesangial cells in the glomeruli, no thickening of the basement membrane, and no glomerular sclerosis and interstitial fibrosis (C). Patient 2 (D-I): CT scan reveals pulmonary nodules with cavity formation, and patchy infiltration (D), and maxillary sinusitis (E); HE stains for renal biopsy showed minimal change, mild mesangial cell hyperplasia in glomerulus (F), similar to patient 1; Bronchoscopy shows mucosal nodule lymphoid hyperplasia from pharynx to the entire airway (G-I).
fimmu-12-670312-g001.jpg
PMC8113859_02_fimmu-12-670312-g001.jpg
f1
CT also showed pulmonary nodules with cavity formation, and patchy infiltration, and bilateral maxillary sinus and ethmoid sinusitis ( Table 1 ,  Figures 1D, E ). Due to recurrent and refractory lung infections, she underwent bronchoscopy during hospitalization, showing mucosal nodule lymphoid hyperplasia in the entire airway ( Figures 1G-I ). Lung biopsy suggested inflammatory cells infiltration ( Figure 2 ) and absence of granulomatous lesions, and renal biopsy pathology indicated mild glomerular disease ( Figure 1F ).
Immunohistochemical analyses for p110delta, CD3, and CD20. Compared with control (A, D), expression of p110delta (brown signal) in lung tissue and lymph node sections from patient 1 (B, E) and 2 (C, F) significantly increased. Many inflammatory cells infiltrated around the airway and in the lung parenchyma (H, I, K, L). Relative to control (G, J), CD3+ T cells (H, I, brown signal) and CD20+ B cells (K, L, brown signal) significantly increased, especially CD3+ T cells. The control lung sample was from a child's lung tumor resection, and lymph node sample was from a child with reactive lymph node hyperplasia.
fimmu-12-670312-g002.jpg
PMC8113859_02_fimmu-12-670312-g002.jpg
f2
Lung biopsy suggested inflammatory cells infiltration ( Figure 2 ) and absence of granulomatous lesions, and renal biopsy pathology indicated mild glomerular disease ( Figure 1F ). Immunohistochemical staining of p110delta, CD3, and CD20 were performed in biopsy tissues of both patients taken previously ( Figure 2 ). Increased expression of p110delta was found in histological sections of the lung and lymph node compared with the control, indicating increased recruitments of p110delta expressing cells ( Figures 2B, C, E, F ). T cells ( Figures 2H, I, K, L ). This study was approved by the Ethic Review Board of Children's Hospital, Zhejiang University School of Medicine (2019-IRB-105).