Characteristics of isatuximab-derived interference in serum protein electrophoresis and immunofixation, and an absence of sustained in vivo interference due to belantamab mafodotin and denosumab.

OBJECTIVES: Some therapeutic monoclonal antibodies, like daratumumab and elotuzumab, produce interfering monoclonal bands on serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Whether other common therapeutic antibodies also produce interference has not been systematically evaluated. DESIGN AND METHODS: SPEP/IFE from patients receiving isatuximab (48 patients), belantamab mafodotin (BM; 41), and denosumab (41) were retrospectively reviewed for therapeutic antibody interference. Cases exhibiting isatuximab interference were quantified and the maximum duration of isatuximab effect was evaluated. To characterize band position, neat human serum was spiked with BM or denosumab at supratherapeutic concentrations. Band migration patterns were compared on SPEP and IFE, with band position expressed relative to other constant protein fractions. RESULTS: Isatuximab-induced IFE interference was common (81.3 % of evaluated patients) with a maximum observed duration of 8 weeks. 10.4 % of isatuximab patients had IgG kappa monoclonal gammopathies that co-migrated with the drug; this subset could benefit from HYDRASHIFT 2/4 isatuximab testing. 8.3 % of IFE cases were negative for an isatuximab band but showed large, endogenous M-spikes migrating elsewhere. All patients in this group expired within 1 year of this finding. We hypothesize that an inability to detect isatuximab in this setting corresponds to a large residual myeloma burden that reduces isatuximab serum concentration. This observation may serve as a negative prognostic factor. Spiking studies demonstrated that BM and denosumab produce interference in vitro, but sustained interference was not observed in >40 treated patients. CONCLUSIONS: Therapeutic antibody interference in patients receiving isatuximab is common, and can persist for at least 8 weeks after administration. >10 % of patients receiving isatuximab may benefit from HYDRASHIFT testing post-therapy. In contrast, BM and denosumab fail to produce sustained interference in treated patients.

A pen as an intermediate target becomes a secondary projectile.

Firearm projectiles striking intermediate targets have the potential to create secondary projectiles, which can produce identifiable patterns of injury. We present a case in which a father, manipulating a handgun, was demonstrating how the firing pin worked to his adolescent son. He placed a pen inside the barrel of the gun for demonstration but did not recognize that a bullet was loaded into the firing chamber. The weapon was discharged causing fatal injury to the son. The pen, as an intermediate target, created identifiable injuries on the decedent, which were consistent with typical patterns of injury seen with secondary projectiles including a discrepant number of skin defects to number of counted projectiles and pseudo-stippling. Recognition of these identifiable patterns of injury in intermediate target involved gunshot wound cases can help support other autopsy findings and scene investigation.

Does MEST-C score predict outcomes in pediatric Henoch-Schönlein purpura nephritis?

BACKGROUND: Children with Henoch-Schönlein purpura nephritis (HSPN) have an increased risk of chronic kidney disease (CKD). Renal biopsy diagnostic of HSPN is graded using the International Study of Kidney Disease in Children criteria, which do not predict outcomes. The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with histologically identical IgA nephropathy, but evidence of its utility in pediatric HSPN is lacking. Our hypothesis was that MEST-C scores predict outcomes in children with HSPN. METHODS: A retrospective cohort analysis of data from 32 children with HSPN who underwent renal biopsy was performed. We used logistic regression and receiver operator characteristic curves to analyze the ability of MEST-C to predict the composite outcome of hypertension (blood pressure ≥ 95% for age/sex/height), CKD (estimated glomerular filtration rate < 90 mL/min/1.73 m2), or proteinuria (urine protein-to-creatinine ratio > 0.2 mg/mg). RESULTS: The median age at diagnosis was 7.9 years (IQR 5.8, 11.7); 56% were male, 19% were Hispanic, and 9% were Black. After a median follow-up of 2.7 years, 38% of patients (n = 12) reached the outcome. S1 score was significantly associated with the outcome (OR 7.9, 95% CI 1.5-42.6). S1 accurately predicted the outcome (area under the curve 0.72, 95% CI 0.55-0.88) with 58.3% sensitivity and 85.0% specificity, indicating a positive predictive value of 70.0% and a negative predictive value of 77.3%. CONCLUSIONS: S1 accurately predicted our composite outcome of hypertension, CKD, and proteinuria in a diverse cohort of U.S. children with HSPN. Further investigation is warranted to validate these findings.