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Limitations of CA125 as an index of peritoneal mesothelial cell mass
Andrzej Breborowicz1, Maciej Breborowicz, Malgorzata Pyda
1Department of Pathophysiology, Poznan Medical School, Poznan, Poland. abreb@am.poznan.pl
Background:
CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells.
Methods:
Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1beta, TNF-alpha, and INF-gamma) and the chronic effects of glucose (45 mM) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol.
Results:
Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 mM) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium.
Conclusions:
The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.
Insights
CA125 levels do not reliably indicate mesothelial cell mass or function in peritoneal dialysis patients. Factors like donor age and high glucose impact CA125 release, limiting its use as a sole index.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- CA125 is a common marker for mesothelial cell mass in peritoneal dialysis.
- Direct correlation data between mesothelial cell number, function, and CA125 production is lacking.
Purpose of the Study:
- To investigate the relationship between human peritoneal mesothelial cell properties and CA125 release.
- To assess the impact of cytokines and high glucose on CA125 production and release.
Main Methods:
- Primary human peritoneal mesothelial cells from 32 donors were cultured in vitro.
- CA125 release was measured and correlated with cell number and function.
- Cells were exposed to cytokines (IL-1beta, TNF-alpha, INF-gamma) and high glucose (45 mM) or mannitol.
Main Results:
- Older donor cells released more CA125, but cell number did not correlate with CA125 release.
- CA125 synthesis was independent of monocyte chemoattractant protein 1 and interleukin-6 levels.
- High glucose (45 mM) chronically reduced CA125 content and release, unlike mannitol.
Conclusions:
- CA125 release is influenced by cell properties, donor age, and high glucose, not just cell number.
- CA125 is an unreliable index for mesothelial cell mass and viability in peritoneal dialysis.
- High glucose negatively impacts mesothelial cell CA125 production and release.
