Molecular genetics and metabolism · 2026
C-type lectin 10A [CD301] mRNA is upregulated in symptomatic acute intermittent porphyria and decreases after heme treatment.
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Storjord Elin, Anderson Karl E, Bonkovsky Herbert L, Murti Abhishek, Tollåli Geir, Moghe Akshata, Wang Bruce, Emblem Åse, Brekke Ole-Lars, Karlsen Bård Ove
Аннотация
BACKGROUND: Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by neurovisceral attacks and the most common acute hepatic porphyria (AHP). We aimed to identify novel blood biomarkers by analyzing differentially expressed genes in whole blood from symptomatic AIP patients and matched controls, and also before and during treatment of acute attacks with heme.
METHODS: mRNA profiling by RNA-seq was performed on whole blood from six AIP patients with elevated urinary porphobilinogen (PBG) and six matched controls in Norway. Differential expression analysis was conducted using DESeq2. C-type lectin domain containing 10A (CLEC10A) mRNA expression was validated by reverse transcription quantitative PCR (RT-qPCR), and CLEC10A protein levels in plasma were measured by ELISA. CLEC10A mRNA profiling by RNA-seq was additionally examined in an independent US dataset from 10 patients with AHP [9 with AIP and 1 with variegate porphyria (VP)], treated with intravenous heme during acute attacks.
RESULTS: CLEC10A mRNA was significantly upregulated in AIP patients compared with matched controls (fold-change (FC) =2.08, adjusted p value = 1.63 × 10-8), and RT-qPCR showed a change in the same direction that did not reach statistical significance (FC 1.62, Wilcoxon matched-pairs signed-rank test, p = 0.094). Plasma CLEC10A protein concentrations were significantly elevated in AIP patients compared with controls (FC 6.68, Wilcoxon matched-pairs signed-rank test, p = 0.03). In the US patients, CLEC10A expression decreased significantly following heme treatment (log2-FC = -1.16; FC of 0.45, adjusted p value = 3.09 × 10-5). The AIP patients in Norway exhibited elevated plasma levels of 24 of 27 measured cytokines (p < 0.05), without corresponding increases in cytokine mRNA in blood consistent with extra-leukocytic sources for these biomarkers.
CONCLUSION: CLEC10A is upregulated in AIP patients with prior symptoms and decreases following heme treatment for acute attacks, suggesting its potential as a marker of biochemically active disease and treatment response. These findings highlight a previously underappreciated link between immune dysregulation and metabolic dysfunction in AIP.
STUDY REGISTRATION: ClinicalTrials.gov Identifiers: NCT01617642, NCT02935400, and NCT02180412.
METHODS: mRNA profiling by RNA-seq was performed on whole blood from six AIP patients with elevated urinary porphobilinogen (PBG) and six matched controls in Norway. Differential expression analysis was conducted using DESeq2. C-type lectin domain containing 10A (CLEC10A) mRNA expression was validated by reverse transcription quantitative PCR (RT-qPCR), and CLEC10A protein levels in plasma were measured by ELISA. CLEC10A mRNA profiling by RNA-seq was additionally examined in an independent US dataset from 10 patients with AHP [9 with AIP and 1 with variegate porphyria (VP)], treated with intravenous heme during acute attacks.
RESULTS: CLEC10A mRNA was significantly upregulated in AIP patients compared with matched controls (fold-change (FC) =2.08, adjusted p value = 1.63 × 10-8), and RT-qPCR showed a change in the same direction that did not reach statistical significance (FC 1.62, Wilcoxon matched-pairs signed-rank test, p = 0.094). Plasma CLEC10A protein concentrations were significantly elevated in AIP patients compared with controls (FC 6.68, Wilcoxon matched-pairs signed-rank test, p = 0.03). In the US patients, CLEC10A expression decreased significantly following heme treatment (log2-FC = -1.16; FC of 0.45, adjusted p value = 3.09 × 10-5). The AIP patients in Norway exhibited elevated plasma levels of 24 of 27 measured cytokines (p < 0.05), without corresponding increases in cytokine mRNA in blood consistent with extra-leukocytic sources for these biomarkers.
CONCLUSION: CLEC10A is upregulated in AIP patients with prior symptoms and decreases following heme treatment for acute attacks, suggesting its potential as a marker of biochemically active disease and treatment response. These findings highlight a previously underappreciated link between immune dysregulation and metabolic dysfunction in AIP.
STUDY REGISTRATION: ClinicalTrials.gov Identifiers: NCT01617642, NCT02935400, and NCT02180412.