Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.BackgroundAnaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined.MethodsImmunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control.ResultsIn normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine.ConclusionsOur results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN

Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants

Kubota T., Nagata M., Takagi K., et al. Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants. Journal of Human Genetics, (2024); https://doi.org/10.1038/s10038-024-01284-z.Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis. Using whole-exome sequencing (WES), we identified compound heterozygous variants of the SCN4A gene encoding the voltage-gated sodium channel of the skeletal muscle (hNav1.4), c.2429T>A p.L810Q and c.4556T>C p.F1519S, in all three deceased infants. A functional analysis conducted using the whole-cell patch-clamp technique revealed loss-of-function defects in both variant channels, with F1519S exhibiting a complete loss of ionic current and L810Q showing a reduced channel opening. These findings support the pathogenicity of SCN4A variants in NIHF and underscore the significance of functional studies in elucidating genotype-phenotype correlations. Furthermore, our study emphasizes the diagnostic value of WES in cases of NIHF in where standard genetic testing fails to identify causative variants

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection

新型コロナウイルス排出と粘膜抗体の関係を解明 --呼吸器ウイルスのヒト間伝播を制御・予防する第一歩--. 京都大学プレスリリース. 2023-12-25.Articles: Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection. 京都大学プレスリリース. 2023-12-25.Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics

Familial Mediterranean Fever with Onset at 66 Years of Age

The patient was a 68-year-old woman who had experienced recurrent febrile episodes since 66 years of age. Despite various examinations and treatments, the etiology remained unclear. Further examinations following another referral failed to uncover the cause. Therefore, despite her age, it was presumed that she had familial Mediterranean fever. An analysis of the familial Mediterranean fever (MEFV) gene detected heterozygous L110P, E148Q, and R202Q mutations. No further febrile episodes occurred after colchicine treatment was initiated. Familial Mediterranean fever presenting in patients in their sixties is extremely rare

Continuous Inflammation and Ascites 10 Months after the Initiation of Peritoneal Dialysis

A 38-year-old man underwent peritoneal dialysis (PD) in May 2011 due to chronic renal failure with chronic glomerulonephritis. In early February 2012, he underwent laparoscopy to salvage and correct a malpositioned PD catheter. The laparoscopic intra-abdominal findings revealed turbid ascites and multiple fibrin lumps, despite the patient\u27s lack of history of peritonitis. Based on these findings, in addition to the presence of continuous inflammation and ascites, a diagnosis of pre-encapsulating peritoneal sclerosis was suspected, and the treatment was switched from PD to hemodialysis. The administration of prednisolone at a dose of 20 mg/day and peritoneal lavage resulted in a decrease in the ascites and fibrin lumps

Continuous Inflammation and Ascites 10 Months after the Initiation of Peritoneal Dialysis

A 38-year-old man underwent peritoneal dialysis (PD) in May 2011 due to chronic renal failure with chronic glomerulonephritis. In early February 2012, he underwent laparoscopy to salvage and correct a malpositioned PD catheter. The laparoscopic intra-abdominal findings revealed turbid ascites and multiple fibrin lumps, despite the patient's lack of history of peritonitis. Based on these findings, in addition to the presence of continuous inflammation and ascites, a diagnosis of pre-encapsulating peritoneal sclerosis was suspected, and the treatment was switched from PD to hemodialysis. The administration of prednisolone at a dose of 20 mg/day and peritoneal lavage resulted in a decrease in the ascites and fibrin lumps