Incidence and Relapse Triggers of Childhood Idiopathic Nephrotic Syndrome between 2006 and 2016: A Population-Based Study in Fukushima, Japan.

Childhood idiopathic nephrotic syndrome (NS) is defined by proteinuria and hypoproteinemia. The incidence of childhood idiopathic NS varies with age, race, residential areas, and social conditions. In Japan, its incidence was estimated to be 6.49 cases/100,000 children. Our study aimed to investigate the incidence, characteristics, and rate of relapse of idiopathic NS in Fukushima between 2006 and 2016. Overall, 158 children aged from 6 months to 15 years old (65.8% male) developed idiopathic NS (median age at onset, 5.3 years). The peak age at onset was three years. The average annual incidence of childhood idiopathic NS was 5.16 (range, 3.47-9.26) cases/100,000 children. The highest incidence was in 2011, which was the year of the Great East Japan Earthquake and nuclear power plant accident, and reportedly caused psychological distress in the children at the time. Conversely, the five-year birth cohort showed minor difference from 2008 to 2012. The rate of incidence in males aged < 5 years was thrice greater than in females of the same age and almost the same for males and females aged 11-15 years. Of 507 total relapses in 115 NS children, common triggers of relapses were steroid discontinuation or reduction and infection. The average annual incidence of childhood NS based on the Fukushima population was lower than previously reported in Japan, and the annual incidence has changed over an 11-year period. These changes may be affected by social or environmental factors, including mental stress associated with lifestyle changes after the disaster.

Clinical characteristics of HNF1B-related disorders in a Japanese population.

BACKGROUND: Hepatocyte nuclear factor 1ß (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. METHODS: We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. RESULTS: Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m2; p = 0.0091). CONCLUSION: We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.

Comparison of long-term follow-up outcomes between multiple-drugs combination therapy and tonsillectomy pulse therapy for pediatric IgA nephropathy.

BACKGROUND: To clarify the long-term efficacy of multiple-drugs combination therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory findings as well as the prognosis for IgAN patients treated with each treatment at long-term follow-up. METHODS: We collected data on 61 children who had been diagnosed with severe IgAN. The children were retrospectively divided into two groups. Group 1 consisted of 44 severe IgAN children treated with PWDM, and Group 2 consisted of 17 severe IgAN children treated with TPT. The clinical features, pathological findings, and prognosis were analyzed for both groups. RESULTS: The mean urinary protein excretion, serum creatinine, IgA levels, MESTCG scores, and percentage of glomeruli showing crescents in both groups at the second renal biopsy were lower than those at the first renal biopsy. At the time of the second biopsy, the IgA level in Group 2 was lower than that in Group 1; however, there were no significant differences in the mean urinary protein excretion, frequency of hematuria, serum albumin, creatinine, or e-GFR between the two groups. At the most recent follow-up, there were no significant differences in prognosis between the groups. CONCLUSIONS: Our study suggested that PWDM and TPT are effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN.

Serum IgA/C3 and glomerular C3 staining predict severity of IgA nephropathy.

BACKGROUND: The aim of this study was to determine whether serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining predict outcome in IgA nephropathy. METHODS: We collected data for 44 IgA nephropathy children treated with multi-drug combination therapy. The children were retrospectively divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A, IgA/C3 ratio >2.68 (median) and glomerular C3 staining ≥2.0, n = 9; group B, IgA/C3 ratio >2.68 and glomerular C3 staining <2.0, n = 7; group C, IgA/C3 ratio <2.68 and glomerular C3 staining ≥2.0, n = 7; and group D, IgA/C3 ratio <2.68 and glomerular C3 staining <2.0, n = 21. Clinical features; pathology at the first and second renal biopsy and at the latest follow up; and prognosis were analyzed for the four groups. RESULTS: At the most recent follow up, urinary protein excretion, incidence of hematuria, and serum creatinine in group A were all higher than in group D. At the second biopsy, crescent absence/presence ratio; mesangial hypercellularity, segmental glomerulosclerosis or adhesion, endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis as well as crescents and global glomerulosclerosis (MESTCG) score; and clonicity index in group A were higher than in group D. All patients in group D had normal urine, and the prevalence of persistent nephropathy in group A was higher than in group D. CONCLUSIONS: Serum IgA/C3 ratio and glomerular C3 staining can predict outcome in IgA nephropathy.

Long-term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy.

BACKGROUND: The aim of this study was to clarify the long-term efficacy of tonsillectomy plus methylprednisolone pulse therapy (tonsillectomy pulse therapy [TMP]) for pediatric immunoglobulin A nephropathy (IgAN). The clinical and laboratory findings as well as the prognosis for IgAN treated with TMP at long-term follow up were evaluated. METHODS: We collected data on 33 IgAN children treated with TMP. The children were retrospectively divided into two groups. Group 1 consisted of 18 children treated with TMP as the initial therapy, and group 2 consisted of 15 children treated with TMP as rescue therapy for IgAN relapse. The clinical features, and laboratory and pathological findings, including those at first and second renal biopsy as well as at the latest follow up, were analyzed for both groups. RESULTS: Mean urinary protein excretion, incidence of hematuria, and serum creatinine in groups 1 and 2 were all decreased significantly after TMP compared with beforehand. The percentage of glomeruli showing crescents after TMP in groups 1 and 2 was significantly lower than before TMP. At the most recent follow up, 94% of patients in group 1 and 87% in group 2 had normal urine, 6% in group 1 and 13% in group 2 had minor urinary abnormalities, and no patients in either group had active renal disease or renal insufficiency. CONCLUSIONS: TMP is effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN both as an initial and as a rescue treatment.

Differences in clinical findings, pathology, and outcomes between C3 glomerulonephritis and membranoproliferative glomerulonephritis.

BACKGROUND: To clarify the clinical manifestations of pediatric complement component C3 glomerulonephritis (C3GN), we retrospectively evaluated differences in the clinicopathological findings and prognosis between C3GN and immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). METHODS: Thirty-seven patients diagnosed with "idiopathic MPGN" were enrolled in this retrospective study. The patients were divided into two groups, with Group 1 consisting of 19 patients diagnosed with IC-MPGN and Group 2 consisting of 18 patients diagnosed with C3GN. The clinical findings and the prognosis were investigated for both groups. RESULTS: Thirteen patients in Group 2 were identified by mandatory annual school screening for urinary abnormalities. The incidence of macro-hematuria and the frequency of low serum C4 values were lower in Group 2 patients than in Group 1 patients. At the time of the second renal biopsy, urinary protein excretion, incidence of hematuria, frequency of low serum C3 values, and scores for mesangial proliferation, glomerular sclerosis, and interstitial fibrosis were higher in Group 2 patients than in Group 1 patients. At the most recent follow-up examination, the number of patients categorized as non-responding or with end-stage renal disease was higher in Group 2 patients than in Group 1 patients. CONCLUSIONS: Our results suggest that the treatment response and prognosis of patients with C3GN are worse than those of patients with IC-mediated MPGN. Therefore, in the clinical context regarding treatment options and prognosis, it may be useful to classify idiopathic MPGN as C3GN or IC-MPGN. In addition, long-term follow-up of C3GN is necessary.

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis.

BACKGROUND: We investigated the efficacy of rituximab and low-dose cyclosporine combination therapy for focal segmental glomerulosclerosis (FSGS) in children with steroid-resistant nephrotic syndrome (SRNS). METHODS: Five FSGS children with SRNS were treated twice with rituximab and low-dose cyclosporine (CyA) combination therapy (RTX-CyAT). The clinical features and laboratory data were investigated before and after RTX-CyAT, and the outcomes were assessed. RESULTS: Prednisolone (PSL) was discontinued 3 months after RTX-CyAT in all patients. The number of CD19-positive cells decreased to <1% of all white blood cells in all patients at 1 month after RTX-CyAT, and was maintained at this level for 259.6 ± 68.2 days. All patients remained in remission for the duration of the decrease in CD19-positive cells to <1%. Two patients also remained in remission throughout the observation period, with three patients having a single relapse at 333 ± 89 days (range, 231-376 days) after RTX-CyAT. In all patients, the mean steroid and CyA doses after RTX-CyAT were lower than those before RTX-CyAT. CONCLUSIONS: RTX-CyAT is effective in FSGS patients with SRNS and may ameliorate the side-effects of PSL and immunosuppressive drugs.

Serum myeloid-related protein 8/14 in minimal change- and glomerulonephritis-related nephrotic syndrome.

BACKGROUND: Myeloid-related protein 8/14 (MRP8/14) forms stable heterodimers and is the major calcium-binding protein secreted by activated granulocytes and monocytes. We evaluated whether serum MRP8/14 level is a useful indicator for a differential diagnosis of glomerulonephritis (GN)- and minimal change disease (MC)- related nephrotic syndrome (NS). METHODS: Serum MRP8/14 complex was evaluated in 37 NS patients with MC or GN. These patients were divided into two groups. Group 1 consisted of 13 NS patients with MC, and group 2 consisted of 24 NS patients with GN. Group 2 was further divided into four subgroups: IgA nephropathy (IgAN; n = 5), Henoch-Schönlein purpura nephritis (HSPN; n = 6), focal segmental glomerulosclerosis (FSGS; n = 12), and acute GN Poststreptococcal acute glomeruloNephritis (PSAGN; n = 1). RESULTS: The clinical manifestations, laboratory findings, serum MRP8/14 level, and renal accumulation of MRP8 were investigated for each group. No significant inter-group differences were observed for serum total protein, serum albumin, or blood urea nitrogen and urinary protein excretions. Mean serum MRP8/14 in the IgAN, HSPN, FSGS, and PSAGN groups was higher than in group 1. Further, the mean glomerular and interstitial MRP8 staining scores in the IgAN, HSPN, and PSAGN groups were higher than in group 1. CONCLUSIONS: Serum MRP8/14 level may be a useful indicator for differential diagnosis between GN- and MC- related NS.

The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice.

BACKGROUND: Recombinant human soluble thrombomodulin (rhTM) is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. In order to clarify the efficacy of rhTM for the treatment of typical hemolytic uremic syndrome (t-HUS), we examined changes in renal damage in t-HUS mice treated with rhTM or vehicle alone. METHODS: We used severe and moderate t-HUS mice injected with shiga toxin (Stx) and lipopolysaccharide (LPS). The severe t-HUS mice were divided into two subgroups [an rhTM subgroup (Group A) and a saline subgroup (Group B)] along with the moderate t-HUS mice [an rhTM subgroup (Group C) and a saline subgroup (Group D)]. Groups E and F were healthy mice treated with rhTM or saline, respectively. RESULTS: All mice in Group B died at 80-90 h post-administration of Stx2 and LPS whereas all mice in Group A remained alive. Loss of body weight, serum creatinine level, endothelial injury and mesangiolysis scores at 24 h after administration in the t-HUS mice treated with rhTM were lower than those in t-HUS mice treated with saline. The levels of hemoglobin at 6 h and platelet counts at 24 h after administration in Group A were higher than those in Group B. Serum interleukin (IL)-6, IL-1ß and tumor necrotic factor (TNF)-α levels at 24 h after administration in Group A were lower than those in Group B. Serum C5b-9 levels at 24 h after the administration and serum fibrinogen degradation product (FDP) at 72 h after the administration of Stx2 and LPS were lower in Group A than in Group B. CONCLUSIONS: These results indicate that rhTM might afford an efficacious treatment for t-HUS model mice via the inhibition of further thrombin formation and amelioration of hypercoagulant status.

Incidence and prognosis of systemic lupus erythematosus in a 35 year period in Fukushima, Japan.

BACKGROUND: We examined the epidemiology, clinical manifestations, and prognosis of pediatric systemic lupus erythematosus (SLE) in Fukushima Prefecture, Japan over a 35 year period. METHODS: We collected the medical records of 37 patients diagnosed with SLE between 1977 and 2013. These children were divided into two groups. group 1 consisted of 19 patients who were diagnosed between 1977 and 1995, and group 2 consisted of 18 patients diagnosed between 1996 and 2013. The epidemiology, clinical features, and prognosis were retrospectively compared between the two groups. RESULTS: The mean number of patients per 100,000 children per year for group 1 and group 2 was 0.33 ± 0.25 and 0.35 ± 0.30, respectively. The duration from onset of symptoms to treatment in group 2 was shorter than that in group 1, but the clinical and laboratory findings at onset did not differ between the two groups. All patients were treated with prednisolone, and 17 patients in group 1 and 18 in group 2 were treated with methylprednisolone pulse therapy. The frequency of cyclophosphamide treatment decreased whereas the frequency of cyclosporine, tacrolimus and mizoribine pulse therapy increased in group 2. SLE disease activity index (SLEDAI) score at the latest follow up in group 2 was lower in group 1. The survival rate was 84% in group 1 and 100% in group 2. CONCLUSION: The frequency and severity of SLE in group 1 were similar to those in group 2, and the prognosis of SLE in group 2 was better than that in group 1.

Characteristics of viruses derived from nude mice with persistent measles virus infection.

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 10(2) PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 10(4) PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.

Efficacy of recombinant human soluble thrombomodulin for childhood hemolytic uremic syndrome.

Recombinant human soluble thrombomodulin (rhTM) is a promising therapeutic natural anticoagulant and is used clinically for the treatment of disseminated intravascular coagulation (DIC). Herein is reported the cases of two HUS children treated with rhTM. The patients were diagnosed as having typical HUS on the basis of thrombocytopenia, hemolytic anemia, acute renal failure, and the detection Escherichia coli 0157. I.v. rhTM was started as an anti-coagulant drug. At 2 days after the first treatment in both patients, fibrin/fibrinogen degradation products and d-dimer levels were significantly decreased, and there was a subsequent slight improvement in thrombocytopenia, and a decrease in serum lactate dehydrogenase level. Urinary protein excretion gradually diminished and a decrease in serum creatinine level was observed. The patients did not require dialysis therapy. The present results suggest that rhTM may be a safe and effective treatment for DIC complicated with HUS in children.

Role of vascular endothelial growth factor and angiopoietin 1 in renal injury in hemolytic uremic syndrome.

BACKGROUND/AIMS: The recovery process from renal injury in hemolytic uremic syndrome (HUS) remains obscure. In order to clarify the role of vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) in the renal recovery from HUS, we produced a model of mild HUS and examined the renal recovery process. METHODS: We investigated three groups of mice. Group 1 consisted of mice that received an injection of Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS); group 2 consisted of mice that received an injection of low dose of Stx2 and LPS, and group 3 consisted of control mice. RESULTS: Serum Cr levels in group 1 were greater than those in group 2, and all mice in group 1 died, whereas all mice in group 2 remained alive. Endothelial injury at 24 h in group 1 was higher than in group 2. Electron-microscopic findings demonstrated that the endothelial cells formed immature capillary-like lumina from 7 to 28 days with increases in the expression of CD31-positive cells. Glomerular VEGF expression decreased at 72 h in group 1, but gradually increased in group 2. Glomerular Ang-1 expression peaked from 72 h to 28 days. Ang-1 expression was frequently found in the endothelial cell region of vesicle walls simultaneous with increased CD31-positive staining. CONCLUSION: Our findings suggest that VEGF and Ang-1 play important roles in the recovery process, particularly in the regeneration of endothelial injury.

Development of common variable immunodeficiency in IgA- and IgG2-deficient patients with systemic lupus erythematosus.

BACKGROUND: There have been few reports on children who developed common variable immunodeficiency (CVID) in association with immunoglobulin A (IgA) and IgG2 deficiencies and systemic lupus erythematosus (SLE). CASE-DIAGNOSIS/TREATMENT: Our patient experienced nephrotic syndrome and acute respiratory distress syndrome (ARDS) caused by influenza A/H1N1 virus infection at 5 years of age. A diagnosis of IgA and IgG2 deficiency and SLE was made on the basis of severe proteinuria, hematuria, hypocomplementemia, high anti-DNA antibody and antinuclear antibody (ANA) titers, and malar rash. However, these clinical signs and symptoms and laboratory features disappeared after the administration of methylprednisolone pulse therapy and prednisolone. For the 5 years following the initial treatment for SLE, the patient experienced a number of infections and had a low serum total IgG level; she was eventually diagnosed with CVID. The administration of intravenous immunoglobulin (IVIG) was required to prevent subsequent infections, and no relapse of SLE was observed. CONCLUSION: We report the development of CVID in an IgA- and IgG2-deficient patient with SLE on the basis of multiple episodes of infection. To prevent the development of CVID in IgA- and IgG2-deficient patients with SLE, it is important to prevent immune dysregulation by the avoidance of infections through the use of IVIG therapy.

Uteroglobulin-related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital.

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.

Successful therapy with tonsillectomy for severe ISKDC grade VI Henoch-Schönlein purpura nephritis and persistent nephrotic syndrome.

Henoch-Schönlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis involving the capillaries and the deposition of IgA immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. We report here a 13-year-old girl with Henoch-Schönlein purpura nephritis (HSPN) of International Study of Kidney Disease in Children (ISKDC) grade VI and persistent nephrotic syndrome despite receiving conventional therapy, such as prednisolone, methylprednisolone and urokinase pulse therapy and plasmapheresis (PP). The patient was treated with tonsillectomy, which subsequently decreased proteinuria, induced the disappearance of microscopic hematuria, and improved renal pathological findings. A regimen of methylprednisolone and urokinase pulse therapy plus PP with tonsillectomy may be an effective and useful therapy for some children with severe HSPN children of ISKDC grade VI and persistent nephrotic syndrome.

Relapse of nephrotic syndrome triggered by Kawasaki disease.

Minor infections, allergies, insect bites, and bee stings are commonly reported causes of nephrotic syndrome (NS). Herein, we report, to the best of our knowledge, the first case of NS relapse due to Kawasaki disease (KD). An 8-year-old boy presented with high fever of 4-day duration. He had developed steroid-dependent NS at the age of 4 years and remained in remission after steroid and mizonbin therapy. Renal biopsy, performed at the age of four, showed minimal change (MC) disease. Upon examination, the patient fulfilled 5 of 6 criteria for KD under the Japanese diagnostic guidelines, with positive proteinuria. He was diagnosed with NS relapse caused by KD. Proteinuria resolved after treatment with intravenous immunoglobulin and cyclosporine A. We present the case of an 8-year-old boy, whose NS relapsed due to KD. To the best of our knowledge, this is the first case report. It is necessary to recognize that KD can trigger relapse of MCNS.

Serum sickness with refractory nephrotic syndrome following treatment with rituximab.

Rituximab (RTX) is effective for treating childhood refractory nephrotic syndrome (NS), such as steroid-dependent (SD), frequently relapsing (FR), and steroid-resistant (SR) NS. While RTX has been proven to be effective in treating SDNS, FRNS, and SRNS, it may cause serum sickness, a rare illness characterized by fever, rash, and arthralgia, 10-14 days after primary antigen exposure or within a few days after secondary antigen exposure, by producing human anti-chimeric antibodies (HACAs). A 17-year-old girl with refractory SDNS treated with RTX and oral cyclosporine A was admitted with fever and arthralgia 10 days after the fifth RTX dose was administered. After RTX was started when she was 14-years-old, SDNS remission was then achieved, and prednisolone was discontinued. Although antibiotics and non-steroidal anti-inflammatory agents were administered, fever and arthralgia continued. After various inspections and clinical course, we considered her as RTX-induced serum sickness (RISS). The patient had an elevated HACA level and was diagnosed with RISS. Fever and arthralgia disappeared 5 days after onset. To the best of our knowledge, this is the first reported case of RISS with NS. Fever, rash, and arthralgia after RTX administration can be the initial symptoms.

The incidence and severity of IgA vasculitis with nephritis over a 10-year period in our hospital.

BACKGROUND: To evaluate the recent frequency of onset and severity of IgA vasculitis with nephritis (IgAVN) in Fukushima Prefecture, we examined the epidemiology and clinico-pathological manifestations of IgAVN in our hospital over a 10-year period. METHODS: We enrolled 18 patients with IgAVN treated between 2004 and 2013 in the Department of Pediatrics, Fukushima Medical University School of Medicine. These patients were divided into two groups; Group 1 consisted of 12 patients with IgAVN hospitalized between 2004 and 2008 and Group 2 consisted of 6 patients with IgAVN hospitalized between 2009 and 2013. The epidemiology, clinical features, laboratory data, pathological findings, and outcome were retrospectively compared between the two groups. RESULTS: The numbers of patients with IgAVN per year in Group 2 were lower than that in Group 1. The frequency of patients with higher than grade IIIb disease in Group 2 (50%) was lower than that in Group 1 (94%); furthermore, the frequency of patients with higher than grade IV disease in Group 2 (0%) was lower than that in Group 1 (50%). CONCLUSIONS: Our findings suggest that the incidence of onset and severity of IgAVN in patients diagnosed between 2009 and 2013 were lower than those in patients diagnosed between 2004 and 2008.

A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.