PURPOSE: The pathophysiology of hypogammaglobulinemia in nephrotic syndrome (NS) remains unknown. We evaluated the differences in the distribution of anti-bacterial antibodies and anti-viral antibodies, and those of immune antibodies and natural antibodies in steroid-sensitive NS. MATERIALS AND METHODS: We examined the antibody status of 18 children who had routine vaccinations. The levels of immnunoglobulin G (IgG), the IgG subclasses, and the antibodies induced by vaccinations such as diphtheria-pertussis-tetanus and measles-mumpsrubella were analyzed in children with steroid-sensitive NS. RESULTS: There was a positive correlation between the albumin and IgG values (r = 0.6, p < 0.01), and the four IgG subclasses were all evenly depressed in the nephrotic children during the acute stage of the disease. The antibodies induced by bacterial antigens were depressed and the seropositivity of anti-viral antibodies tended to be lower than those of age-matched control children during the acute stage. The depressed immune antibody status recovered rapidly in the remission stage of NS, despite corticosteroid treatment. CONCLUSIONS: IgG levels correlated positively with albumin levels, and all antibodies, including immune and natural antibodies, were depressed in the acute stage of NS. Our results suggest that hypogammaglobulinaemia in NS may be associated with intravascular homeostasis of oncotic pressure.
Adolescent ; Antibodies, Bacterial/immunology ; Antibodies, Viral/immunology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin G/immunology ; Male ; Nephrotic Syndrome/*drug therapy/*immunology ; Steroids/*therapeutic use

OBJECTIVES: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. METHODS: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. RESULTS: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD⁺ memory B cells, and IgE⁺ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM⁺IgD⁺ memory B cells, IgM⁺ memory B cells, IgE⁺ memory B cells, IgD⁺ memory B cells, and IgG⁺ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE⁺ memory B cells (P<0.05). CONCLUSIONS Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE⁺ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.
Child ; Humans ; B-Lymphocyte Subsets/metabolism* ; Immunoglobulin E ; Immunoglobulin M ; Nephrotic Syndrome/immunology* ; Prospective Studies ; Glucocorticoids/therapeutic use*

Endogenous ouabain (EO) is a recently found hormone that may be secreted from adrenal cortex. As an endogenous mammalian analogue of cardiac glycosides and an inhibitor of the sodium pump, it regulates the body fluid balance, urine sodium extraction and vasoconstrictive tone, and thus plays an important role in the pathogenesis of hypertension and some other cardiovascular disorders. This articke reviews its biological features, receptor and antibody, detection, effects on diseases and relationship with endothelial cells.
Adrenal Cortex ; metabolism ; Animals ; Antibodies ; therapeutic use ; Humans ; Hypertension ; etiology ; Nephrotic Syndrome ; etiology ; Ouabain ; immunology ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; immunology ; physiology

Adjuvants, Immunologic ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Male ; Mycobacterium bovis ; immunology ; Nephrotic Syndrome ; immunology ; prevention & control ; Nucleic Acids ; therapeutic use ; Polysaccharides, Bacterial ; therapeutic use ; Recurrence

Nephrotic syndrome associated with Tsutsugamushi disease has not been previously reported. We are describing a case of Tsutsugamuchi disease presenting with nephrotic syndrome. A 72-year-old woman presented with fever and generalized edema. Laboratory studies revealed a leukocytosis, hypoalbuminemia, and hypercholesterolemia. Her urine protein excretion was 5.4 g/day. The anti-Tsutsugamushi antibody test was strongly positive (1:2,560). A renal biopsy was performed, and pathologic findings revealed membranous glomerulonephritis. The patient's clinical symptoms improved markedly after treatment with doxycycline.
Aged ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Bacterial/blood ; Biopsy ; Doxycycline/therapeutic use ; Female ; Glomerulonephritis, Membranous/diagnosis/*etiology ; Humans ; Nephrotic Syndrome/diagnosis/*etiology ; Orientia tsutsugamushi/immunology ; Scrub Typhus/*complications/diagnosis/drug therapy/microbiology ; Treatment Outcome

OBJECTIVEAutosomal recessive steroid-resistant nephrotic syndrome (SRNS) is a subgroup of familial nephrotic syndrome. A causative gene has been identified, that is NPHS2, in chromosome 1q25-31, which encodes podocin. This study aimed to detect NPHS2 mutation in a Chinese family with SRNS.

METHODSRenal biopsy was performed on the proband and her sibling for routine histologic and immunohistochemical investigation and electron microscopic examination. The expressions of podocin, nephrin, alpha-actinin and WT1 in glomeruli of the proband were detected by indirect immunofluorescence. Peripheral blood samples were collected for genetic analysis from the proband and her parents, and 53 adults with normal urinalysis. Genomic DNA was isolated from peripheral blood leucocytes. Eight exons of NPHS2 were amplified by polymerase chain reaction. Mutational analysis was performed using denaturing high-performance liquid chromatography (DHPLC) and DNA fragments with aberrant elution profiles of both strands revealed by DHPLC were re-amplified and sequenced directly.

RESULTSThe histologic findings on kidney biopsies were focal segmental glomerulosclerosis. In controls, the distribution of staining with P35, rabbit against a human podocin recombinant protein (amino acids 135 - 383 = all the C-terminal part of the protein downstream the transmembrane domain), and P21, rabbit against a human podocin recombinant protein (amino acids 15 - 89 = all the N-terminal part of the protein upstream the transmembrane domain) showed a linear pattern along glomerular capillary walls on glomeruli, and the fluorescent intensity of the staining with P35 was intensely positive. The fluorescent intensity of the staining with P21 was positive. In the proband, the distribution of the staining with P35 showed uneven and nonlinear, and the fluorescent intensity of the staining with P35 was weakly positive. The staining with P21 was negative. The area, location, distribution and fluorescent intensity of the staining with nephrin, alpha-actinin and WT1 on glomeruli of the proband were the same as those in the controls. The DHPLC elution profiles of exon 4 of NPHS2 from the proband and her parent were aberrant. The chromatograms by sequencing detected in the exon 4 of NPHS2 showed a composite heterozygous mutation of both 467_468insT and 503G > A in the proband, a heterozygous mutation of 503G > A in her father, and a heterozygous mutation of 467_468insT in her mother, respectively.

CONCLUSIONThe study demonstrated for the first time a novel mutation, 503G > A, of NPHS2 in Chinese kindred with autosomal recessive SRNS. A significantly decreased or negative expression was also revealed in glomeruli of the proband stained with two kinds of anti-podocin antibodies.

Actinin ; analysis ; Adult ; Aged ; Base Sequence ; Child ; DNA Mutational Analysis ; Drug Resistance ; Female ; Fluorescent Antibody Technique, Direct ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; Kidney ; immunology ; pathology ; Male ; Membrane Proteins ; analysis ; genetics ; Mutation ; genetics ; Nephrotic Syndrome ; genetics ; Pedigree ; Polymerase Chain Reaction ; Proteins ; analysis ; WT1 Proteins ; analysis

OBJECTIVERecent studies suggest that T cell dysfunction, especially IL-4, may be involved in the pathogenesis of steroid sensitive nephrotic syndrome (SSNS). The aim of this study was to investigate the association between the polymorphisms in variable numbers of tandem repeat region (VTR) of IL-4 gene and childhood SSNS.

METHODThe polymorphism in the IL-4 gene was identified by using the polymerase chain reaction and direct sequencing methods in 55 Chinese children with SSNS, who were followed-up for at least 1 year, and 115 healthy Chinese adult blood donors as controls. A variable number of tandem repeat (VNTR) region polymorphisms of IL-4 gene were detected, and alleles were designated as IL-4 B1 and B2, corresponding to 2 and 3 repeats, respectively. The serum IgE was also examined in 48 patients before the steroid treatment.

RESULT(1) There were no significant differences in the genotype and allele frequencies between patients with SSNS and normal controls (P > 0.05). (2) The frequencies of B1B1 (96.4%) were significantly higher in SSNS children with frequent relapses (28 patients had more than 3 relapses during the first year of the disease) than in 27 patients without frequent relapses (P < 0.05). (3) Twenty-three patients with frequent relapses showed higher levels of serum IgE (1.98 +/- 0.23 g/L) than 25 patients (IgE: 1.05 +/- 0.19 g/L) without frequent relapses (P < 0.05), and the patients with B1B1 (38 patients) also had higher serum IgE levels than patients with B1B2 and B2B2 (10 patients) (P < 0.05).

CONCLUSIONThe results suggest that IL-4 VNTR B1B1 genotype might be a predictor for the frequent relapse in childhood SSNS in Chinese.

Adolescent ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunoglobulin E ; blood ; Infant ; Interleukin-4 ; genetics ; Male ; Minisatellite Repeats ; Nephrotic Syndrome ; drug therapy ; genetics ; immunology ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Recurrence ; Steroids ; therapeutic use