Anti-glomerular basement membrane (anti-GBM) nephritis is a rare but highly aggressive cause of rapidly progressive glomerulonephritis (RPGN). Early recognition is essential, as delayed diagnosis leads to irreversible kidney damage and poor prognosis. We report an 8-year-old girl with anti-GBM nephritis initially misattributed to kidney involvement of IgA vasculitis (IgAV). Diagnosis was confirmed by markedly elevated anti-GBM antibodies and kidney biopsy findings. Despite plasma exchange and immunosuppressive therapy, kidney function deteriorated to kidney failure within several months. This case provides an important clinical insight for pediatric nephrologists: worsening urinary findings or kidney function during follow-up of IgAV should prompt consideration of RPGN and appropriate serological screening, as well as timely kidney biopsy, rather than being attributed solely to IgAV nephritis.
OBJECTIVE:This study aimed to characterize the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of subcutaneous belimumab in pediatric patients with active systemic lupus erythematosus (SLE) receiving standard therapy. METHODS:This single-arm, multicenter, open-label trial (GSK study 200908; ClinicalTrials.gov identifier: NCT04179032) used three-weight-band subcutaneous dosing of belimumab 200 mg every week (qw) for pediatric patients weighing ≥50 kg, every 10 days for pediatric patients weighing 30 to <50 kg, and every 2 weeks (q2w) for pediatric patients weighing 15 to <30 kg. The pharmacokinetic profile was characterized by observed concentration at week 12 and population pharmacokinetics (popPK) estimates derived from concentrations over 52 weeks. Pharmacodynamics, safety, and exploratory efficacy (≥4-point reduction from the baseline Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI] score) were descriptively evaluated. Alternative two-weight-band subcutaneous dosing (≥40 kg: 200 mg qw; 15 to <40 kg: 200 mg q2w) was simulated to predict pharmacokinetics for this regimen. RESULTS:Patients weighing 30 to <50 kg had lower observed belimumab concentrations than those weighing ≥50 kg (week 12 geometric mean 82.8 vs 134 μg/mL), but popPK analyses predicted the three weight bands to be generally consistent and in alignment with established adult subcutaneous and pediatric intravenous exposures. The pharmacodynamic and safety profile was consistent with known belimumab effects. By week 52, 18 of 22 patients (81.8%) had a ≥4-point reduction from baseline SELENA-SLEDAI scores. Hypothetical two-weight-band dosing simulations predicted consistent exposure across weight bands and in line with established exposures in SLE. CONCLUSION:Exposure following subcutaneous belimumab administration in pediatric patients is consistent with approved usage; these findings, along with consistent safety and efficacy data, support subcutaneous belimumab use for pediatric patients with SLE.
OBJECTIVES:This study aimed to evaluate the diagnostic performance of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR-2019) classification criteria of systemic lupus erythematosus (SLE) and to clarify the clinical characteristics of Japanese childhood-onset SLE (cSLE). METHODS:We retrospectively analyzed clinical data registered in the Paediatric Rheumatology International Collaboration Unit Registry (PRICURE) version 2 up to March 31, 2023. Frequencies of individual items within the EULAR/ACR-2019 criteria were compared with those observed in a Japanese adult SLE cohort. RESULTS:A total of 105 patients with cSLE, 19 with Juvenile dermatomyositis (JDM), 27 with primary Sjögren's disease (pSjD), and 9 with mixed connective-tissue disease (MCTD) were included. The sensitivity of the EULAR/ACR-2019 criteria was 97.1%. The specificity was 94.7% for JDM, 92.6% for pSjD, 55.6% for MCTD, and 87.3% for all disease controls. cSLE patients in this cohort more frequently exhibited renal involvement, low serum C3 or C4 levels, and positivity for antiphospholipid and anti-double-stranded DNA antibodies, but joint symptoms were less common than in adult SLE patients. CONCLUSIONS:Although the EULAR/ACR-2019 criteria are generally applicable, the limited specificity for MCTD necessitates careful differential diagnosis. Japanese cSLE is commonly characterized by renal involvement, hypocomplementemia, and SLE-related autoantibody positivity.
We describe a rare and aggressive case of multiple myeloma (MM) characterized by extensive lymph node involvement, loss of CD138 expression, and adipophilin (ADP)-positive cytoplasmic vacuolization, highlighting the role of lipid metabolism in disease aggressiveness. An 83-year-old woman presented with painless cervical lymphadenopathy and widespread osteolytic lesions. Bone marrow examination confirmed MM, while lymph node biopsy showed diffuse infiltration of atypical lymphoid cells with numerous tingible body macrophages, initially mimicking a high-grade lymphoma. Immunophenotyping showed CD3/CD5/CD20/CD23 negativity, focal CD138/CD79a positivity, diffuse MUM1 and κ-light chain positivity, and a high Ki-67 index. Compared with bone marrow plasma cells, lymph node MM cells exhibited prominent cytoplasmic vacuoles and nuclear enlargement. Immunohistochemistry demonstrated ADP positivity in lymph node lesions but not in bone marrow MM cells, suggesting metabolic reprogramming toward lipid utilization. Despite anti-myeloma therapy, the disease rapidly progressed, and the patient died within two months. This case underscores the clinical significance of CD138 down-regulation as a marker of dedifferentiation and poor prognosis, and suggests that altered lipid metabolism may contribute to the aggressiveness of metastatic MM. To the best of our knowledge, this is the first MM case with lymph node involvement showing CD138 down-regulation and ADP positivity.
INTRODUCTION:Juvenile dermatomyositis (JDM) exhibits varying clinical features depending on myositis-specific autoantibodies (MSA), with racial differences. The association between JDM and human leukocyte antigen (HLA) has been reported, but data from Japan are lacking. Therefore, this study aimed to investigate HLA susceptibility in patients with JDM in Japan. METHODS:Data of patients with JDM from six facilities across Japan were collected and compared to those of healthy controls. HLA analysis was performed using a next-generation sequencer, covering 11-loci. RESULTS:The study included 39 patients with JDM: female 23 (59%), mean age at onset 6.2 years. Among MSA, anti-TIF1γ antibody was present in 12/35 (34.3%), anti-MDA5 antibody in 7/35 (20%), anti-NXP2 antibody in 6/28 (21.4%), and MSA negative in 3/35 (8.6%). Five HLA alleles were detected more frequently in patients with JDM. HLA-DPA1*02:02 (odds ratio (OR) 8.84, corrected p-value (pc) < 0.001), HLA-DPB1*05:01 (OR 5.35, pc < 0.001), HLA-C*14:02 (OR 4.07, pc 0.037), DQB1*04:01 (OR 3.01, pc 0.049), and HLA-DRB4*01:03 (OR 2.92, pc 0.008) were significantly more common in patients with JDM than in healthy controls. HLA-DRB1*04:05 was associated with interstitial lung disease (ILD) (OR 5.7; 95% CI 1.09-30.07, p = 0.043). CONCLUSION:HLA-DPA1*02:02, HLA-DPB1*05:01,HLA-C*14:02, HLA-DQB1*04:01, and HLA-DRB4*01:03 are potentially novel susceptibility HLA in Japanese patients with JDM. The high incidence of ILD in Asian patients with anti-MDA5 antibodies may be attributable to HLA-DRB1*04.
