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OBJECTIVES: To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. METHODS: A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. RESULTS: Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. CONCLUSIONS: Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.
Subject(s)
Kidney Diseases, Cystic , Child , Humans , Retrospective Studies , Syndrome , Kidney Diseases, Cystic/genetics , Mutation , PhenotypeABSTRACT
Background: To observe the changes of autophagy-related protein levels in peripheral blood lymphocytes before and after sirolimus treatment in children with systemic lupus erythematosus (SLE). Methods: Children with SLE were randomly divided into two groups, 28 in the traditional treatment group and 28 in the sirolimus group. Fifteen healthy children who were in the same period were collected as the normal control group. Clinical laboratory indexes, the percentage of routine lymphocytes, complement C3, complement C4, serum Anti-dsDNA and SLEDAI were detected. Results: At 3 and 6 months after treatment, compared with the traditional treatment group, the percentage of routine lymphocytes in the sirolimus group increased (P = 0.03), SLEDAI score and positive rate of Anti-dsDNA decreased (P = 0.01). Compared with normal children, the expression of microtubule-associated protein 1 light chain 3 (LC3) protein in peripheral blood lymphocytes was significantly higher (P = 0.006); peripheral blood expression of P62/SQSTM1 (sequestosome 1) protein in lymphocytes decreased (P = 0.02). Conclusion: Sirolimus can play a role in the treatment of systemic lupus erythematosus by regulating the level of autophagy.
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BACKGROUND: Purpuric nephritis is the most common secondary glomerular disease in childhood. Its prevalence in children has been steadily rising in recent years. OBJECTIVE: To explore the characteristics and pathogenesis of changes in peripheral blood lymphocyte subsets and immune function in children with Henoch-Schonlein purpura nephritis. METHODS: The study included 104 children with Henoch-Schonlein purpura, divided into nephritis (HSPN) group (68 cases) and non-nephritis (NHSPN) group (36 cases), and 15 normal children. The rate-scatter turbidimetric method was utilized to determine the immunoglobulins IgA, IgG, IgM, C3 and C4, and the flow cytometry technique was employed to detect the levels of lymphocyte subsets including CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, NK, etc. RESULTS: Compared with the control group, the CD3+, CD4+, CD8+ and NK cell levels of peripheral blood mononuclear cells significantly decreased (P<0.05), and the CD19+ level significantly elevated (P<0.05) in the HSPN group and the NHSPN group whereas the HSPN group had a more significant change than the NHSPN group (P<0.05). Compared with the control group, the serum immunoglobulin IgA and IgG of the HSPN group and the NHSPN group significantly increased, and the IgM, C3, and C4 significantly decreased (P<0.05); while the HSPN group had a more significant change than the NHSPN group (P<0.05). CONCLUSION: Immune dysfunction in children with HSPN is specifically manifested as low cellular immune function, which leads to increased secretion of inflammatory mediators, activates B cells, and further increases the secretion of immunoglobulins, leading to the occurrence of small vasculitis.
Subject(s)
IgA Vasculitis , Nephritis , Humans , Immunity , Leukocytes, Mononuclear , Lymphocyte SubsetsABSTRACT
Objective: To identify the gene mutation of Stormorken syndrome and review the published Stromal Interaction Molecule 1 (STIM1) mutation phenotype. Methods: We described the clinical and molecular aspects of a Chinese female with Stormorken syndrome by laboratory tests, muscle biopsies, and genetic analysis. We used this information to summarize all the mutation sites reported in the literature. We also reviewed the clinical features of published cases with a gain of function mutations of STIM1. Results: A 12-year-old Chinese female presented with skin purpura in the lower limbs and stroke-like episodes. Muscle biopsy and microscopic examination revealed atrophy in her skeletal muscle. Genetic analysis identified a novel heterozygous missense mutation, a c.1095G>C transition (NM_003156.3), which caused a p.K365N amino acid substitution in the protein and affected a STIM1-orai1-activation region (SOAR). Conclusions: The novel variant c.1095G>C transition (NM_003156.3) was located in the SOAR, which expands the phenotypic spectrum of STIM1 variants in human disorders and may define the molecular basis of Stormorken syndrome.
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BACKGROUND: To investigate the similarities and differences of renal clinical and renal pathology between IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN) in children. METHODS: A total of 237 children with IgAN and 190 children with IgAVN were included. The general conditions, clinical characteristics, final diagnosis, clinical and pathological classification of the children were intercepted at the time of admission, and the retrospective comparative analysis was carried out. RESULTS: The results showed that the median course of disease in IgAN group was longer than that in IgAVN group (p = 0.02). Patients with IgAN had a significantly higher duration of infection than the patients with IgAVN (p = 0.03). The white blood cell count (WBC), hemoglobin (HGB) in IgAN group were significantly lower than that in IgAVN group (p = 0.02). The serum creatinine in IgAN group was higher than that in IgAVN group (p = 0.02). Patients with IgAN and IgAVN had statistically significant differences in pathological typing between clinical types: hematuria and proteinuria, nephrotic syndrome and chronic nephritis (p = 0.004). DISCUSSION: The clinical manifestations of IgAN and IgAVN were similar, but the onset of IgAN was hidden and the clinical manifestations were relatively serious. Renal pathology was mainly glomerulosclerosis and renal tubular atrophy. IgAVN was characterized by acute onset and good renal function. Renal pathology was dominated by endothelial hyperplasia and crescent formation. These differences did not support the hypothesis that the two diseases are the same.
Subject(s)
Glomerulonephritis, IGA , IgA Vasculitis , Nephritis , Child , Humans , IgA Vasculitis/complications , Glomerulonephritis, IGA/complications , Retrospective Studies , KidneyABSTRACT
OBJECTIVE: To study the role of autophagy in the development of systemic juvenile idiopathic arthritis (sJIA) by analyzing the expression of microtubule-associated protein 1 light chain 3-II (LC3-II), myeloid differentiation factor 88 (MyD88), and suppressor of T-cell receptor signaling 1 (STS-1) in peripheral blood lymphocytes of children with sJIA. METHODS: A total of 26 children with sJIA were enrolled as the sJIA group, and 26 healthy children were enrolled as the control group. Western blot was used to measure the protein expression of LC3-II, STS-1, and MyD88 in peripheral blood lymphocytes. Immunofluorescence assay was used to measure the expression of LC3-II in the cytoplasm of lymphocytes. Pearson correlation analysis was used to assess the correlation between indices. RESULTS: Compared with the control group, the sJIA group had significant increases in the expression of LC3-II, STS-1, and MyD88 (P<0.05). In the sJIA group, the expression of LC3-II was positively correlated with that of MyD88 (r=0.478, P<0.05), and the expression of STS-1 was also positively correlated with that of MyD88 (r=0.817, P<0.05). CONCLUSIONS: There is high expression of LC3-II in peripheral blood lymphocytes of children with sJIA, suggesting that the development of sJIA may be associated with excessive expression of autophagy. STS-1 may induce autophagy by activating some signaling pathways, and MyD88 may participate in autophagy through the Toll-like receptor signaling pathway.
Subject(s)
Arthritis, Juvenile , Autophagy , Child , HumansABSTRACT
OBJECTIVE: To observe the clinical effect of integrative medicinal therapy in treating children Henoch-Schonlein purpura (HSP) and its preventive effect on complicated renal impairment. METHODS: One hundred and twenty children with HSP were equally randomized into two groups, the treated group and the control group. Both were treated with conventional Western medical therapy, but Sanhuang Qingxue Yin (SQY, a Chinese herbal drug) was given additionally to the treated group. Besides, a group consisted of 30 healthy children was set up as a normal control. Changes of symptoms, physical signs, routine urine, plasma endothelin-1 (ET-1) and urinary levels of beta2-microglobulin (beta2-MG), albumin (ALB) and immunoglobulin G (IgG) before and after treatment were observed, and the recurrence was monitored. RESULTS: The cure rate and the total effective rate in the treated group were 80.0% and 98.3%, while those in the control group were 61.7% and 88.3%, showing significant differences between groups (P < 0.05); the disappearance time of clinical symptoms was shorter in the treated group than in the control group, also showing a significant difference (P < 0.01); after 1-month treatment, levels of plasma ET-1, and urinary beta2-MG, ALB and IgG were improved in the treated group, reaching the levels opproximate to those in the normal control (P > 0.05), significant difference was shown as compared with those in the control group and with those before treatment respectively (P < 0.01, P < 0.05). The recurrent rate was 13.33% in the treated group and 30.0% in the control group, and they were statistically different (P < 0.05). CONCLUSION: The integrative medicinal therapy is good for treating HSP in children, it could not only obviously relieve clinical symptoms, shorten the illness course and reduce the recurrent rate, but also effectively prevent the occurrence of renal impairment.
