Inter- and intra-individual differences regarding SARS-CoV-2 and influenza vaccination in pediatric kidney transplant recipients: An observational study.

In kidney transplant recipients (KTRs), viral infection can lead to antibody and/or T-cell mediated rejection, resulting in kidney transplant dysfunction. Therefore, it is critical to prevent infections. However, KTRs exhibit suboptimal responses to SARS-CoV-2 and/or influenza vaccines, partly due to immunosuppressant therapy. Inter- and intra-individual differences in the biological responses to vaccines may also affect patients' antibody production ability. This study included KTRs who received an messenger RNA SARS-CoV-2 vaccine (3 doses), and an inactivated quadrivalent influenza vaccine (1 or 2 doses). We measured the patients' total antibody titers against SARS-CoV-2 spike antigen, and hemagglutination inhibition (HI) titers against influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. Five patients were eligible for this study. Of these 5 KTRs, two produced anti-SARS-CoV-2 spike antibody titers to a seroprotective level, and also produced HI titers against A/H1N1 to a seroprotective level. Another 2 KTRs did not produce seroprotective anti-SARS-CoV-2 antibody titers, but produced seroprotective HI titers against A/H1N1. The remaining KTR produced a seroprotective anti-SARS-CoV-2 antibody titer, but did not produce a seroprotective HI titer against A/H1N1. The 2 KTRs who did not produce seroprotective anti-SARS-CoV-2 antibody titers following vaccination, later developed COVID-19, and this infection increased their titers over the seroprotective level. This study demonstrated that inter- and intra-individual differences in biological responses to vaccines should be considered in pediatric KTRs, in addition to immunosuppressant effects. Personalized regimens, such as augmented or booster doses of vaccines, could potentially improve the vaccination efficacy against SARS-CoV-2 and influenza.

Neonatal onset of Niemann-Pick disease type C in a patient with cholesterol re-accumulation in the transplanted liver and inflammatory bowel disease.

BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited and neurodegenerative disorder. Approximately 10% of NPC patients have acute liver failure and sometimes need liver transplantation (LT), and 7% reportedly develop inflammatory bowel disease (IBD). We report the case of a girl with NPC who had a re- accumulation of cholesterol in the transplanted liver and NPC-related IBD. CASE REPORT: The patient underwent living donor liver transplantation (LDLT) due to severe acute liver failure caused by an unknown etiology inherited from her father. At 1 year and 6 months (1Y6M), she developed neurological delay, catalepsy, and vertical supranuclear gaze palsy. The foam cells were found in her skin, and fibroblast Filipin staining was positive; hence, she was diagnosed with NPC. It was identified that her father had NPC heterozygous pathogenic variant. At 2 years, she had anal fissure, skin tag and diarrhea. She was diagnosed with NPC-related IBD, using a gastrointestinal endoscopy. Three years after LT, liver biopsy revealed foam cells and numerous fatty droplets. At 8 years, broken hepatocytes and substantial fibrosis were observed. She died from circulation failure due to hypoalbuminemia at 8Y2M. CONCLUSIONS: In NPC, load of cholesterol metabolism is suggested to persist even after LT. LDLT from NPC heterozygous variant donor was insufficient to metabolize cholesterol overload. In NPC patients, the possibility of cholesterol re-accumulation should be considered when LT is performed. NPC-related IBD should be considered when NPC patients have anorectal lesions or diarrhea.

Glucocorticoid effects on bone strength in children with renal diseases.

AIM: Glucocorticoids (GC) are essential medicines for idiopathic steroid-sensitive nephrotic syndrome (ISSNS) and IgA nephropathy (IgAN), with good clinical results. However, they cause bone fragility. The aim of this study was to elucidate GC effects on bone strength assessed as bone mineral density (BMD) and bone quality, using bone turnover markers (BTM), in children with ISSNS or IgAN. METHODS: Eleven children with ISSNS and 13 with IgAN were included. All the patients received GC treatment according to each protocol. The BMD and BTM-serum alkaline phosphatase (S-ALP), tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and undercarboxylated osteocalcin (S-ucOC)-were measured from the initiation of steroid treatment (STx) to the end of STx in both groups. RESULTS: In ISSNS, S-ALP and S-ucOC levels were decreased significantly at 1 month. BMD and S-TRACP-5b levels showed no significant change through this observation period. In IgAN, BMD and S-ALP levels were decreased significantly at 1 and 3 months, respectively, and recovered to baseline at 10 months after the initiation of GC dosage reduction. S-TRACP-5b levels were decreased significantly at 3 months and remained lower than at baseline through the observation period. In both groups, S-ucOC levels did not directly reflect bone strength. CONCLUSION: This study clarified the following three points regarding GC effects on bone strength in children with ISSNS or IgAN: first, S-ALP is a more sensitive bone quality marker than S-TRACP-5b; second, BMD loss was observed only when both S-ALP and S-TRACP-5b levels decreased, and third, S-ucOC levels do not directly reflect bone strength.

Efficacy of plasma exchange with a high dose of acyclovir for disseminated varicella infection.

In individuals treated with immunosuppressive therapies, the varicella-zoster virus (VZV) infection can become disseminated and lead to a life-threatening condition. There is currently no established treatment strategy for this life-threatening condition. Here, we describe a case where plasma exchange (PE) with a high dose of acyclovir (ACV) ameliorated the severe effects, including VZV-hemophagocytic lymphohistiocytosis (VZV-HLH) and disseminated intravascular coagulation (DIC), in a 9-year-old girl with steroid-dependent nephrotic syndrome. This 9-year-old girl experienced frequent relapse steroid-dependent nephrotic syndrome. She had been treated with steroids, tacrolimus, mizoribine, and rituximab. She had not previously received a varicella vaccine. She was admitted with only one vesicular rash. At admission, a serum test revealed 1.6 × 106 copies/mL of VZV DNA. The patient rapidly developed VZV-HLH and DIC. A combination of a high dose of ACV, immunoglobulin, and steroid pulse therapy could not improve these severe complications. Therefore, PE was applied. PE with a high dose of ACV successfully reduced serum VZV DNA from 7.5 × 106 to 2.8 × 104 copies/mL. This reduction in the VZV DNA copy number suggested that the combination of PE and a high dose of ACV was effective in treating a disseminated VZV infection. To the best of our knowledge, this is the first report showing that PE with a high dose of ACV ameliorated the severe complications of disseminated VZV by reducing the VZV DNA copy number.