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Objective:To investigate the clinical manifestations, pathological characteristics, treatment and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in 13 children.Methods:The clinical and pathological data of 13 cases of AAV in children′s Hospital of Nanjing Medical University from June 2000 to December 2021 were retrospectively analyzed.Results:Among the 13 cases, 12 cases were diagnosed with microscopic polyangiitis (MPA) and 1 case was granulomatosis with polyangiitis (GPA), including 10 females and 3 males. The onset age ranged from 3 years and 11 months to 13 years and 10 months. The most frequently involved organ was the kidney (12 cases, 92.3%), followed by respiratory system (7 cases, 53.8%), skin (5 cases, 38.5%), digestive system (4 cases, 30.8%), nervous system (4 cases, 30.8%) and cardiovascular system (3 cases, 23.1%). There were 10 cases with orthotic anemia, 7 cases with positive antinuclear antibody, and 3 cases with mildly decreased complement C3. Among the 12 children with renal impairment, 9 cases were accompanied by abnormal renal function at the beginning of the disease. Renal biopsy was classified according to the Berden as follows: sclerotic in 5 cases, crescentic 3 cases, focal in 2 cases and mixed in 2 cases. All children were treated with glucocorticoid combined with immunosuppressant. During the follow-up time from 8 months to 128 months, 4 cases acquired complete remission, 8 cases achieved partial remission and 1 case recurred after complete remission, and 7 cases progressed to chronic kidney disease stage 5. Three children with complete remission underwent repeated renal biopsy, including 2 cases of mixed type and 1 case of crescent type initially, and all changed to focal type.Conclusions:AAV in children occurs mainly in school-age female, and most of AAV in children is MPA. The clinical manifestations are various. Most of them have renal damage and anemia, and lung damage is also common. Patients with skin purpura onset may be misdiagnosed as Henoch-Schonlein purpura, and AAV with ANA positive or complement reduction should exclude systemic lupus erythematosus. Once the renal function is abnormal in AAV, especially estimated glomerular filtration rate<60 ml·min -1·(1.73 m 2) -1 and the pathological classification is sclerotic type or crescent type, it is difficult to reverse even after active treatment. Early diagnosis and treatment are very important for AAV.
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Objective@#To summarize the clinical features and genetic analysis results of 10 children with Dent disease.@*Methods@#The clinical data and gene test results of 10 boys aged from 8 months to 12 years with Dent disease diagnosed in Children's Hospital of Nanjing Medical University from January 2014 to July 2017 were analyzed retrospectively.@*Results@#All patients had insidious onset, 5 cases were found to have proteinuria on routine urine examination after hospitalization duo to other diseases, 4 cases were admitted to hospital because increased foams in the urine, and 1 case was found to have proteinuria on health checkup. All cases presented with low molecular weight proteinuria, urine protein electrophoresis showed that the proportion of low molecular weight protein was greater than 50%, 7 cases had nephrotic-range proteinuria, but none had hypoproteinemia. Six cases had hypercalciuria, 3 cases had nephrocalcinosis, 1 case had nephrolithiasis, 2 cases had glomerular microscopic hematuria, in 1 case urine glucose wa weakly positive but blood glucose was normal. All patients had normal renal function, normal serum calcium, no hypophosphoremia and none had rickets. Genetic analysis results showed that 7 patients with variants in the CLCN5 gene, including 2 nonsense variants (p.R637X, p.Y143X), 3 missense variants (p.A540D, p.G135E, p.G703V), 1 deletion variant (exons 9, 10, 11, 12, 13, 1 missing), and 1 frameshift variant (p.T260Tfs*10). Three cases had missense variants of OCRL gene (p.I274T, p.I371T, p.F399S). Except for p.R637X and p.I274T, the other 8 cases had newly discovered variants. Five patients underwent a renal biopsy, the biopsy revealed focal global glomerulosclerosis in 3 patients, mild mesangial proliferative glomerulonephritis in 1 patient and renal minimal change in 1 patient. Mild focal tubular atrophy and interstitial fibrosis were noted in three cases. Mild segmental foot process effacement was noted under electron microscope in all five cases.@*Conclusions@#All the children with Dent disease had insidious onset, low molecular weight proteinuria is the main clinical manifestation, most cases presented with nephrotic-range proteinuria, but there was no hypoalbuminemia, some cases were not associated with hypercalciuria. The pathogenic genes in most cases were CLCN5 and a few were OCRL. The types of genetic variation include missense variant, nonsense variant, deletion variant and frameshift variant. Although Dent disease is a renal tubular disease, renal biopsy suggests that most cases are associated with glomerular lesions.
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<p><b>OBJECTIVE</b>To type the Chinese Anaplasma phagocytophilum isolates by Multispacer typing (MST).</p><p><b>METHODS</b>Based on the genomes of the 4 published Anaplasma strains, 4 genomic sequences were analyzed by Mauve 2.3.1 software and variable spacer sequences were selected for designing primers with the bio-software Primer Premier 5.0. A total of 11 Chinese A. phagocytophilum isolates, obtained from different areas of China during 2009-2012 were assayed by the MST. Twenty two intergenic sequences for each isolate tested and the reference A. phagocytophilum strain Webster and A. phagocytophilum strain HZ were concatenated in the order of HGA-mst 1F/1R-mst 2F/2R, HGA-mst 22F/22R.</p><p><b>RESULTS</b>Twenty two pairs of primers were successfully used for typing the Human granulocytic anaplasmosis (HGA) strains in the study. Those 22 intergenic sequences exhibited a great diversity among the strains tested and each of the strain tested was identified as unique genotype, according to the alignment analysis of the 22 concatenated intergenic sequences. Of these single nucleotide polymorphism (SNPs) identified in the study, the nucleotide transitions shared the highest percentage (60.2%, 251/417) and then the nucleotide transversion, accounted for 23.0% (96/417) and the indel events (insertion/deletion) were observed of 16.7% (70/417)SNPs. Phylogenetic analysis indicated that the 5 strains from patients (LZ-H1, LZ-H2, LZ-H3, LZ-H4, LZ-H5) from Laizhou areas, Shandong province and 1 tick strain (LZ-T1) from Haemaphysalis longicornis collected from the same areas where the patients lived were grouped in the same clan with the reference A. phagocytophilum strain Webster and strain HZ. Beijing isolates (BJ-H1) grouped with Xinjiang isolates (XJ-H1 and XJ-H3) while another tick isolates from Laizhou areas (LZ-T2) and another Xinjiang human isolate(XJ-H2)were in the same clan, which was closely related to the isolates from severe patients in Laizhou.</p><p><b>CONCLUSION</b>Chinese HGA isolates exhibited a great diversity of intergenic regions. MST seemed a valuable tool for the detection and tracing for any endemic strains of Anaplasma during the outbreak investigations in the public health events.</p>
Subject(s)
Anaplasma phagocytophilum , Classification , Genetics , Bacterial Typing Techniques , Methods , China , DNA, Ribosomal Spacer , Genetics , Polymorphism, Single NucleotideABSTRACT
Objective To analyze the clinical and immunological features of 45 pediatric patients with lupus nephritis (LN). Methods Forty-five LN patients were included in this study. Clinical, pathological data and immunological parameters were retrospectively analyzed. Results Forty-five LN patients had 6 males and 39 females, with the mean onset age of (10.9 ± 2.8) years. Acute nephritis was the most common type, accounting for 42.2%. Nephrotic syndrome accounted for 31.1%. Renal biopsy showed class II (17.8%), III (4.4%), IV (48.9%), V (2.2%), V+III (6.7%)and V+IV (13.3%)in 42 cases. The remis-sion rate reached 91.1%in the early therapeutic stage, and 15.0%patients recurred after 24-month follow-up. Conclusions The clinical manifestations of LN children are diverse. The renal pathology is complex. The clinical manifestations in part of the chil-dren are not consistent with renal pathology.
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ABSTRACT:In recent years ,there has been high prevalence of murine typhus in Yunnan Province ,People's Republic of China .A large outbreak of murine typhus occurred in Xishuangbanna Prefecture ,Yunnan Province in 2010 .However ,not all cases were confirmed by laboratory assays ;therefore ,field epidemiologic and laboratory investigations of murine typhus in Xishuangbanna Prefecture were conducted in 2011 .Blood samples were collected from clinical diagnostic cases at the acute and convalescence stages of murine typhus in Xishuangbanna Prefecture ,Yunnan Province ,from June to September of 2011 ,and blood and spleen samples were collected from mice sharing the same habitats as the patients .Immunofluorescence assays were used to test for the presence of IgM and IgG antibodies against Rickettsia typhi in sera from patients and mice .Real‐time PCR was used to detect the groEL gene of R .typhi in blood clots from patients at the acute stage and in spleen tissue from mice .A total of 1 157 clinically diagnosed murine typhus cases occurred in Xishuangbanna Prefecture ,Yunnan Province in 2011 ,with an incidence of 102 .10/100 000 .Of these cases ,80 were investigated by laboratory assays and 74 of 80 patients were confirmed to have murine typhus .The coincidence rate between the clinical diagnosis and laboratory detection was 92 .50% .The positivi‐ty rate for IgG antibodies against R .typhi was 14 .0% (14/100) for Rattus f lavipectus ,while the rate by PCR was 9 .0%(9/100) .That laboratory diagnoses confirmed that the severity of the murine typhus outbreak in Xishuangbanna cannot be ig‐nored .The distribution of host animals transmitting R .typhi underscores this conclusion .
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Spotted fever caused by spotted fever group rickettsiae (SFGR) is found throughout China. During 2007—2008, 28 human SFGR isolates and 34 rat SFGR isolates including 15 isolates from <i>Rattus fulvescens</i>, 5 isolates from <i>R.edwardsi</i>, 7 isolates from <i>Callosciurus erythraeus roberti</i> and 7 isolates from <i>Dremomys rufigenis</i>) were obtained from L929 cell culture. Previous research indicated that the 62 strains of SFGR mentioned above shared not only the same serophenotype but also 100% of identity sequences of 16S rRNA, <i>gltA</i>, <i>ompA</i>, <i>groEL</i> and 17KD, which enabled us to apply multispacer typing (MST) to the 62 SFGR isolates in the study. Six primer pairs, which were used for typing of <i>Rickettsia rickettsii</i> and <i>Rickettsia conorii</i>, were chosen, and the results exhibited greater nucleotide polymorphisms among the 62 isolates tested. A total of 48 distinct genotypes were identified. The dominant genotype, represented by h3 isolates, accounted for 21.7% (13/60) of the isolates tested, and the remaining 47 genotypes were all unique. Phylogenetic analysis showed that all the 48 genotypes could be classified in the same clade, while the genetically related strain, <i>R.heilongjiangensis</i>, was close but not the same as the cluster. We concluded that the genetically diverse of spotted fever group rickettsiae strains are endemic in Chengmai County, Hainan Province, China.
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Spotted fever caused by spotted fever group rickettsiae (SFGR) is found throughout China. During 2007–2008, 28 human SFGR isolates and 34 rat SFGR isolates including 15 isolates from <i>Rattus fulvescens</i>, 5 isolates from <i>R. edwardsi</i>, 7 isolates from <i>Callosciurus erythraeus roberti</i> and 7 isolates from <i>Dremomys rufigenis</i>) were obtained from L929 cell culture. Previous research indicated that the 62 strains of SFGR mentioned above shared not only the same serophenotype but also 100% of identity sequences of 16S rRNA, <i>gltA</i>, <i>ompA</i>, <i>groEL</i> and 17KD, which enabled us to apply multispacer typing (MST) to the 62 SFGR isolates in the study. Six primer pairs, which were used for typing of <i>Rickettsia rickettsii</i> and <i>Rickettsia conorii</i>, were chosen, and the results exhibited greater nucleotide polymorphisms among the 62 isolates tested. A total of 48 distinct genotypes were identified. The dominant genotype, represented by h3 isolates, accounted for 21.7% (13/60) of the isolates tested, and the remaining 47 genotypes were all unique. Phylogenetic analysis showed that all the 48 genotypes could be classified in the same clade, while the genetically related strain, <i>R. heilongjiangensis</i>, was close but not the same as the cluster. We concluded that the genetically diverse of spotted fever group rickettsiae strains are endemic in Chengmai County, Hainan Province, China.
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Objective To type the Chinese Anaplasma phagocytophilum isolates by Multispacer typing(MST). Methods Based on the genomes of the 4 published Anaplasma strains,4 genomic senquences were analyzed by Mauve 2.3.1 software and varable spacer sequences were selected for designing primers with the bio-software Primer Premier 5.0. A total of 11 Chinese A. phagocytophilum isolates,obtained from different areas of China during 2009-2012 were assayed by the MST. Twenty two intergenic sequences for each isolate tested and the reference A. phagocytophilum strain Webster and A. phagocytophilum strain HZ were concatenated in the order of HGA-mst 1F/1R-mst 2F/2R,HGA-mst 22F/22R. Results Twenty two pairs of primers were successfully used for typing the Human granulocytic anaplasmosis(HGA) strains in the study. Those 22 intergenic sequences exhibited a great diversity among the strains tested and each of the strain tested was identified as unique genotype,according to the alignment analysis of the 22 concatenated intergenic sequences. Of these single nucleotide polymorphism(SNPs)identified in the study,the nucleotide transitions shared the highest percentage(60.2%,251/417)and then the nucleotide transversion,accounted for 23.0%(96/417) and the indel events (insertion/deletion) were observed of 16.7%(70/417) SNPs. Phylogenetic analysis indicated that the 5 strains from patients (LZ-H1,LZ-H2,LZ-H3,LZ-H4,LZ-H5) from Laizhou areas,Shandong province and 1 tick strain(LZ-T1)from Haemaphysalis longicornis collected from the same areas where the patients lived were grouped in the same clan with the reference A. phagocytophilum strain Webster and strain HZ. Beijing isolates(BJ-H1)grouped with Xinjiang isolates (XJ-H1 and XJ-H3) while another tick isolates from Laizhou areas (LZ-T2) and another Xinjiang human isolate(XJ-H2)were in the same clan,which was closely related to the isolates from severe patients in Laizhou. Conclusion Chinese HGA isolates exhibited a great diversity of intergenic regions. MST seemed a valuable tool for the detection and tracing for any endemic strains of Anaplasma during the outbreak investigations in the public health events.
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Objective To type the Chinese Anaplasma phagocytophilum isolates by Multispacer typing(MST). Methods Based on the genomes of the 4 published Anaplasma strains,4 genomic senquences were analyzed by Mauve 2.3.1 software and varable spacer sequences were selected for designing primers with the bio-software Primer Premier 5.0. A total of 11 Chinese A. phagocytophilum isolates,obtained from different areas of China during 2009-2012 were assayed by the MST. Twenty two intergenic sequences for each isolate tested and the reference A. phagocytophilum strain Webster and A. phagocytophilum strain HZ were concatenated in the order of HGA-mst 1F/1R-mst 2F/2R,HGA-mst 22F/22R. Results Twenty two pairs of primers were successfully used for typing the Human granulocytic anaplasmosis(HGA) strains in the study. Those 22 intergenic sequences exhibited a great diversity among the strains tested and each of the strain tested was identified as unique genotype,according to the alignment analysis of the 22 concatenated intergenic sequences. Of these single nucleotide polymorphism(SNPs)identified in the study,the nucleotide transitions shared the highest percentage(60.2%,251/417)and then the nucleotide transversion,accounted for 23.0%(96/417) and the indel events (insertion/deletion) were observed of 16.7%(70/417) SNPs. Phylogenetic analysis indicated that the 5 strains from patients (LZ-H1,LZ-H2,LZ-H3,LZ-H4,LZ-H5) from Laizhou areas,Shandong province and 1 tick strain(LZ-T1)from Haemaphysalis longicornis collected from the same areas where the patients lived were grouped in the same clan with the reference A. phagocytophilum strain Webster and strain HZ. Beijing isolates(BJ-H1)grouped with Xinjiang isolates (XJ-H1 and XJ-H3) while another tick isolates from Laizhou areas (LZ-T2) and another Xinjiang human isolate(XJ-H2)were in the same clan,which was closely related to the isolates from severe patients in Laizhou. Conclusion Chinese HGA isolates exhibited a great diversity of intergenic regions. MST seemed a valuable tool for the detection and tracing for any endemic strains of Anaplasma during the outbreak investigations in the public health events.