Plasma Mucin-1 (CA15-3) Levels in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations
Petr Vylet'al1, Kendrah Kidd1,2, Hannah C Ainsworth3
1Department of Paediatrics and Inherited Metabolic Disorders, Research Unit of Rare Diseases, First Faculty of Medicine, Charles University, Prague, Czechia.
Introduction:
Patients with ADTKD-MUC1 have one allele producing normal mucin-1 (MUC1) and one allele producing mutant MUC1, which remains intracellular. We hypothesized that ADTKD-MUC1 patients, who have only 1 secretory-competent wild-type MUC1 allele, should exhibit decreased plasma mucin-1 (MUC1) levels. To test this hypothesis, we repurposed the serum CA15-3 assay used to measure MUC1 in breast cancer to measure plasma MUC1 levels in ADTKD-MUC1.
Methods:
This cross-sectional study analyzed CA15-3 levels in a reference population of 6,850 individuals, in 85 individuals with ADTKD-MUC1, and in a control population including 135 individuals with ADTKD-UMOD and 114 healthy individuals.
Results:
Plasma CA15-3 levels (mean ± standard deviation) were 8.6 ± 4.3 U/mL in individuals with ADTKD-MUC1 and 14.6 ± 5.6 U/mL in controls (p < 0.001). While there was a significant difference in mean CA15-3 levels, there was substantial overlap between the 2 groups. Plasma CA15-3 levels were <5 U/mL in 22% of ADTKD-MUC1 patients, in 0/249 controls, and in 1% of the reference population. Plasma CA15-3 levels were >20 U/mL in 1/85 ADTKD-MUC1 patients, in 18% of control individuals, and in 25% of the reference population. Segregation of plasma CA15-3 levels by the rs4072037 genotype did not significantly improve differentiation between affected and unaffected individuals. CA15-3 levels were minimally affected by gender and estimated glomerular filtration rate.
Discussion/Conclusions:
Plasma CA15-3 levels in ADTKD-MUC1 patients are approximately 40% lower than levels in healthy individuals, though there is significant overlap between groups. Further investigations need to be performed to see if plasma CA15-3 levels would be useful in diagnosis, prognosis, or assessing response to new therapies in this disorder.
Insights
Patients with Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 (ADTKD-MUC1) have significantly lower plasma mucin-1 (MUC1) levels compared to healthy individuals. However, substantial overlap exists, limiting its diagnostic utility.
Area of Science:
- Nephrology
- Genetics
- Biochemistry
Background:
- Autosomal Dominant Tubulointerstitial Kidney Disease with MUC1 (ADTKD-MUC1) is characterized by one normal and one mutant MUC1 allele.
- The mutant MUC1 protein is retained intracellularly, impacting MUC1 secretion.
Purpose of the Study:
- To investigate whether ADTKD-MUC1 patients exhibit decreased plasma mucin-1 (MUC1) levels.
- To assess the potential of plasma MUC1 levels, measured by the CA15-3 assay, as a biomarker for ADTKD-MUC1.
Main Methods:
- A cross-sectional study involving 85 ADTKD-MUC1 patients, 249 controls (including ADTKD-UMOD and healthy individuals), and a reference population of 6,850 individuals.
- Plasma MUC1 levels were measured using the serum CA15-3 assay.
Main Results:
- ADTKD-MUC1 patients had significantly lower mean plasma CA15-3 levels (8.6 ± 4.3 U/mL) compared to controls (14.6 ± 5.6 U/mL, p < 0.001).
- A substantial overlap in CA15-3 levels was observed between ADTKD-MUC1 patients and controls.
- Plasma CA15-3 levels were minimally affected by gender and estimated glomerular filtration rate.
Conclusions:
- Plasma CA15-3 levels are approximately 40% lower in ADTKD-MUC1 patients than in healthy individuals, but overlap limits diagnostic use.
- Further research is needed to determine the utility of plasma CA15-3 in ADTKD-MUC1 diagnosis, prognosis, or therapy assessment.
