Study in focus 1

Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study

Lupus nephritis (LN) is one of the major organ complications in children with systemic lupus erythematosus. Mycophenolate mofetil (MMF) is proven to be non-inferior to other drugs such as cyclophosphamide, and azathioprine in the treatment of children with various pathological types of LN. The MMF pharmacokinetics is influenced by various factors such as age, sex, renal impairment, gene polymorphism, and concomitant medication. This population-based observational cohort study was conducted to reveal the relationship between mycophenolic acid exposure and disease response and adverse drug reactions in pediatric lupus nephritis patients. Eighty-six children (70 girls) were included in the study and the MMF dose was 23.09±6.99mg/kg/day, oral steroids and hydroxychloroquine were given. The histological classes of LN were II (3.49%), III±V (26.74%), IV±V (66.28%) and V (3.49%). Up to 6 months, all children were followed up and 27 children lost follow-up at 12 months. The improved renal remission rates were correlated with higher MPA-AUC with thresholds of 29.81 μg/h/mL-1 at 6 months, and 30.63 μg/h/mL−1 at 12 months. The threshold to maintain the hypoactive state of LN (30.96 at 6 months; 31.19 μg/h/mL−1 at 12 months). To avoid the MMF related adverse reactions the observed threshold was 50.80μg/h/mL−1.

This study suggested that the initial and long-term MMF treatment of pediatric LN nephritis should be individualized, and the recommended dose of MPA exposure is 31.19-50.80 μg/h/mL−1.

Study in focus 2

Enrichment of rare variants of hemophagocytic lymphohistiocytosis genes in systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory disease with hallmarks of severe systemic inflammation, which can be accompanied by arthritis. Macrophage activation syndrome (MAS) is one of the life-threatening complications in sJIA. This study evaluated rare variants of familial hemophagocytic lymphohistiocytosis (fHLH) genes in patients with and without MAS in sJIA. Targeted sequencing genes of HLH (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in 524 sJIA cases, and finally 480 cases were included for analysis. The sequencing data from the Atherosclerosis Risk in Communication cohort were used as population control data. The cohort identified 499 variants (369 in control & 161 in sJIA) in six HLH genes. This study identified rare HLH (STXBP2 and UNC13D) variants in patients with sJIA. The UNC13D variant has been associated with MAS. This study concluded the association of HLH gene variants in patients with sJIA and MAS.

References

1.Zhang L, Chen L, Liu X, et al. Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study. Rheumatology (Oxford). 2024;63(SI2):SI180-SI187.

2.Correia Marques M, Rubin D, et al. Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2024;76(10):1566-72.