Anti-SARS-CoV-2 IgG antibody titer after BNT162b2 mRNA COVID-19 vaccination in Japanese patients who underwent renal replacement therapy, hemodialysis, peritoneal dialysis, and kidney transplantation.

BACKGROUND: Coronavirus disease (COVID-19) vaccination is recommended for patients undergoing renal replacement therapy (RRT), including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT). However, the difference in the immune response between RRT patients and healthy individuals after mRNA vaccines remains uncertain. METHODS: This retrospective observational study evaluated the anti-severe-acute-respiratory-syndrome-coronavirus-2 (anti-SARS-CoV-2) IgG antibody acquisition, titers and their changes, normal response rate (reaching titers of healthy individuals), factors associated with a normal response, and effectiveness of booster vaccination in Japanese RRT patients. RESULTS: Most HD and PD patients acquired anti-SARS-CoV-2 IgG antibodies after the second vaccination; however, their antibody titers and normal response rates (62-75%) were low compared with those of healthy subjects. Approximately 62% of KT recipients acquired antibodies, but the normal response rate was low (23%). Anti-SARS-CoV-2 IgG antibody waning occurred in the control, HD, and PD groups, while negative or very low titers remained in KT recipients. Third booster vaccination was effective in most HD and PD patients. However, the effect was mild in KT recipients - only 58% reached a normal response level. Multivariate logistic regression analyses demonstrated that younger age, higher serum albumin level, and RRT other than KT were significantly associated with a normal response after the second vaccination. CONCLUSIONS: RRT patients, particularly KT recipients, exhibited poor vaccine responses. Booster vaccination would be beneficial for HD and PD patients; however, its effect in KT recipients was mild. Further COVID-19 vaccinations using the latest vaccine or alternative procedures should be considered in RRT patients.

Mechanisms underlying the methylglyoxal-induced enhancement of uridine diphosphate-mediated contraction in rat femoral artery.

Although femoral artery dysfunctions, including aberrant vascular reactivity to vasoactive substances, are common in many chronic disorders, such as diabetes and hypertension, their inducible and/or progressive factors remain unclear. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of various chronic disorders. However, its direct correlation with extracellular nucleotides including uridine 5'-diphosphate (UDP) in the femoral artery function is currently unknown. Therefore, we investigated the acute effect of MGO on UDP-induced contraction in the rat femoral artery. MGO (4.2 × 10-4 M for 1 h) enhanced the UDP-induced contraction. This enhancement was not abolished in all conditions, including nitric oxide synthase inhibition, cyclooxygenase inhibition, or endothelial denudation. In the endothelium-denuded arteries, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (10-5 M) suppressed the UDP-induced contraction in both control and MGO-treated groups, while MGO enhanced the p38 MAPK activation regardless of the UDP presence. Moreover, in the endothelium-denuded arteries, the Syk tyrosine kinase inhibitor piceatannol (10-5 M) suppressed the UDP-induced contraction. These results suggest that MGO augments UDP-induced contraction in rat femoral arteries and that this may be partly due to the alterations in the activities of Syk tyrosine kinase and p38 MAPK in the smooth muscle.

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Developing Pancreatic Lesion and Diabetes Mellitus: A Case Report and Review of the Literature.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small blood vessels and causes severe systemic organ injury commonly affecting the lungs and kidney. However, gastrointestinal, especially pancreatic, lesions are rare. We report the case of a 67-year-old Japanese man diagnosed with myeloperoxidase (MPO) AAV who developed pancreatic lesions and diabetes mellitus. The patient was admitted to our hospital due to fever, cough, and weight loss. He developed progressive glomerulonephritis, lung nodules, and pancreatic swelling and mass. Additionally, laboratory examination revealed positive MPO-ANCA and elevated glycated hemoglobin A1c, which were suggestive of diabetes mellitus. Renal biopsy revealed necrotizing crescentic glomerulonephritis and vasculitis in the small arteries. Endoscopic ultrasound-guided fine needle aspiration of the pancreas was performed, and histological findings suggested the possibility of pancreatic vasculitis and parenchymal injury. The patient was diagnosed with AAV, which was managed with glucocorticoids. This improved the renal function and pancreatic lesions. Furthermore, blood glucose levels improved despite treatment with glucocorticoids. These findings suggest that AAV-related pancreatic lesions worsened glycemic control. However, glucocorticoid therapy improved vasculitis and pancreatic lesions, which resulted in improved glycemic control.

A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene.

A single nucleotide polymorphism in the ABCC11 gene, 538G>A (rs17822931), is known to determine human ear wax type. The G/G and G/A genotypes correspond to the wet type, while the A/A genotype corresponds to the dry type. Another earwax determinant, a 27-bp deletion (Δ27) downstream from the rs17822931 site, is a rare variant that leads to the dry phenotype. In a previous report, we found an individual with the G allele who unexpectedly showed the dry type of earwax, leading to the identification of Δ27. We also demonstrated that the Δ27 allele was present in individuals of Japanese, Thai, native North American, Andean, and Bolivian ancestry but absent in those of European and African ancestry. Here, we assessed the Δ27 allele frequency among Japanese and Ukrainian individuals and identified a novel association between the Δ27 and 538G>A mutations. The Δ27 allele frequency was 0.002 (3/1,520; one individual is heterozygous, and another is homozygous) among Japanese individuals and 0 (0/794) among Ukrainians. We also found a previously unreported homozygous genotype for both the Δ27 and A alleles. Our findings suggest that the Δ27 deletion may have occurred in an ABCC11 gene with the 538G>A mutation.

A Case of an Elderly Woman Who Developed Corneal Perforation in the Clinical Course of Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a systemic vasculitis characterized by ANCA positivity and categorized into three main types: microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatous with polyangiitis. Although AAV leads to systemic organ injury, such as of the lungs, kidneys, nerves, and skin, patients with AAV sometimes develop ocular lesions. Here, we report the case of an elderly woman who had been treated for AAV for seven years. She developed scleritis and relapsed twice, with elevation of serum disease markers such as ANCA titer and C-reactive protein. After the decline of these markers due to treatment with additional medication, her scleritis relapsed again and caused a corneal ulcer, which resulted in perforation without obvious marker elevation. She did not present with any symptoms of organ injury, except for ocular lesions. She was treated with surgery, followed by methylprednisolone and rituximab therapy. Subsequently, her ocular lesions and symptoms improved, and she did not relapse. AAV can cause various ocular manifestations. Although C-reactive protein and ANCA titers are useful markers of disease activity and the relapse of AAV complications, including ocular lesions, these markers do not always increase at the time of worsening ocular lesions. Therefore, it is important for clinicians treating patients with AAV to pay careful attention to serum data and physical findings, including the eyes.

Cayman ataxia-related protein is a presynapse-specific caspase-3 substrate.

Caspase plays an important role in apoptosis and physiological processes such as synaptic plasticity. However, the caspase substrate at the synapse is still unknown. Here we used an in vitro cleavage assay with a small-pool human brain cDNA library. We identified the presynaptic protein Caytaxin as a substrate of caspase-3 and caspase-7. Deficiency in Caytaxin causes Cayman ataxia, a disorder characterized by cerebellar dysfunction and mental retardation. Caytaxin cleavage in cerebellar granule neurons is dependent on caspase-3 activation. The cleavage site is upstream of the cellular retinal and the TRIO guanine exchange factor domain, producing a C-terminal fragment that may play an alternative role in inhibiting MEK2 signaling. Thus, we concluded that Caytaxin is a novel substrate of caspase-3 at the presynapse.

Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner.

Mutation of the gene encoding Caytaxin causes human Cayman ataxia by interfering with normal splicing and, in mutant rodents, by reducing normal transcription, which leads to ataxia, dystonia, and mental retardation: These observations suggest that Caytaxin may be crucial for higher brain functions such as motor learning. We generated antibodies against mouse Caytaxin. Interestingly, we found that the expression of Caytaxin is regulated during brain development while quantitative real time RT-PCR indicated that the mRNA level did not change between postnatal days 7 (P7) and P14 in the cerebellum and hippocampus, implying that the expression of Caytaxin may be controlled by a post-transcriptional mechanism. Immunostaining analyses demonstrated that Caytaxin was localized in many brain areas including the cerebellum and hippocampus. Furthermore, Caytaxin was localized to the presynaptic cytosol by the subcellular fractionation of mouse brain and an observation that was confirmed by co-localization studies with synapsin I and VGLUT1. The above data, disease phenotypes, and mutant animals suggest that Caytaxin may be essential for synaptic function. Thus, identifying the role of Caytaxin in synapse maturation may lead to the development of therapeutic interventions for cerebellar ataxia as well as mental disorders.

Protein Concentration of Refractory Ascites in Cancer Patients is Reflected by the Presence and Severity of Peritoneal and Liver Metastasis.

Ascites total protein concentration (A-TP) affects the performance of cell-free and concentrated ascites reinfusion therapy (CART). As the factors determining A-TP remain unclear, we examined peritoneal and liver metastasis. Among 98 patients who received CART, 68 with cancer, ascites from no other apparent cause, and complete CT and A-TP data were recruited. Sixty-six patients (97%) with peritoneal and/or liver metastasis on CT were divided into the peritoneal metastasis group (PM group), peritoneal and liver metastasis group (PM + LM group), and liver metastasis group (LM group). A-TP was highest in the PM group (3.9 g/dL [3.4-4.4]), lowest in the LM group (1.0 g/dL [0.9-2.0]), and broadly dispersed in the PM + LM group (3.3 g/dL [2.0-3.8]). All differences were statistically significant. The percentage of metastasis volume occupying the liver was negatively and significantly related to A-TP in the PM + LM group. Taken together, the presence and severity of peritoneal and liver metastasis may influence A-TP.