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Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation.

Albano L, Rak JM, Azzouz DF, Cassuto-Viguier E, Gugenheim J, Lambert NC - PLoS ONE (2012)

Bottom Line: In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women.Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion.This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases.

View Article: PubMed Central - PubMed

Affiliation: UMC Transplantation Rénale, Hôpital Pasteur, Centre Hospitalo-Universitaire de Nice, Nice, France.

ABSTRACT
Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.

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Typical amplifications of male Mc in female host's DNA.PBMC from a healthy woman (A) and a woman with ESRD (B) tested for male Mc in 10 samples.
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pone-0032248-g002: Typical amplifications of male Mc in female host's DNA.PBMC from a healthy woman (A) and a woman with ESRD (B) tested for male Mc in 10 samples.

Mentions: When both groups were analyzed as a whole, without stratifying by age, parity, or history of transfusion, as illustrated in Figure 1, we detected male Mc in 62% (34/55) of women with ESRD versus only 16% (13/82) of healthy women (p<0.00001). Differences in quantities of Mc between the two groups were also very significant (Figure 1, Figure 2 for typical amplifications and Table S1 for number of wells positive). Levels of Mc ranged from 0 to 1382 gEq/M in women with ESRD and from 0 to 5 gEq/M in controls with a mean number of 98 gEq/M and 0.3 gEq/M respectively (p = 0.0005). We did not find any correlation between Mc levels and the length of time since the last abortion, the number of induced or spontaneous abortions, the length of time since the last transfusion, the length of time since the birth of the last child or last son, or the number of sons or children (data not shown).There was also no relationship between the types of nephropathy (vascular, glomerular, interstitial and polycystic) and the presence or the level of Mc (data not shown).


Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation.

Albano L, Rak JM, Azzouz DF, Cassuto-Viguier E, Gugenheim J, Lambert NC - PLoS ONE (2012)

Typical amplifications of male Mc in female host's DNA.PBMC from a healthy woman (A) and a woman with ESRD (B) tested for male Mc in 10 samples.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293902&req=5

pone-0032248-g002: Typical amplifications of male Mc in female host's DNA.PBMC from a healthy woman (A) and a woman with ESRD (B) tested for male Mc in 10 samples.
Mentions: When both groups were analyzed as a whole, without stratifying by age, parity, or history of transfusion, as illustrated in Figure 1, we detected male Mc in 62% (34/55) of women with ESRD versus only 16% (13/82) of healthy women (p<0.00001). Differences in quantities of Mc between the two groups were also very significant (Figure 1, Figure 2 for typical amplifications and Table S1 for number of wells positive). Levels of Mc ranged from 0 to 1382 gEq/M in women with ESRD and from 0 to 5 gEq/M in controls with a mean number of 98 gEq/M and 0.3 gEq/M respectively (p = 0.0005). We did not find any correlation between Mc levels and the length of time since the last abortion, the number of induced or spontaneous abortions, the length of time since the last transfusion, the length of time since the birth of the last child or last son, or the number of sons or children (data not shown).There was also no relationship between the types of nephropathy (vascular, glomerular, interstitial and polycystic) and the presence or the level of Mc (data not shown).

Bottom Line: In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women.Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion.This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases.

View Article: PubMed Central - PubMed

Affiliation: UMC Transplantation Rénale, Hôpital Pasteur, Centre Hospitalo-Universitaire de Nice, Nice, France.

ABSTRACT
Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.

Show MeSH
Related in: MedlinePlus