REGULATORY T CELLS in PERIPHERAL BLOOD in
women with OVARIAN and PERITONEAL
ENDOMETRIOSIS
Nina Slabe, MD, PhD Hospital for Gynecology and Obstetrics Kranj, Slovenia
• None
DECLARATION OF INTERESTS:
ENDOMETRIOSIS
Ectopic endometrial tissue outside the
uterus
Etyology?
Is endometriosis immune disease?
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
Sampson: Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pritoneal cavity (1927) Meden-Vrtovec: Endometrioza (1993) Ribič-Pucelj: Endoskopske operacije v ginekologiji. Endometrioza (2007) Baldi: Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (2008) Bulun: Endometriosis (2009)
AIM
• Our study aimed to evaluate peripheral blood lymphocyte subpopulations during the menstrual cycle in women with peritoneal and ovarian endometriosis relative to healthy women.
Gleicher: Immune dysfunction - a potential target for treatment in endometriosis (1995) Nothnick: Treating endometriosis as an autoimmune disease (2001) Oosterlynck: Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium (1991)
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
METHODS and MATERIALS
Subjects Study group 65 women
• Ovarian endometriosis • Peritoneal endometriosis
Control group 61 healthy women
Exclusion criteria Rectovaginal endometriosis Pelvic inflamatory disease Polycystic ovary disease Gynecological carcinoma Ovarian cysts of different etiology Use of hormonal treatment in past 3 months
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
Ribič-Pucelj: Globoka infiltrativna endometrioza (2007) Halis: The diagnosis and treatment of deep infiltrating endometriosis (2010)
METHODS and MATERIALS
Flow cytometric analysis B-lymphocytes (CD19+) T-lymphocytes (CD3+) T-helper cells (CD4+) Cytotoxic T-lymphocytes (CD8+) CD4/CD8 NK cells (CD56+/CD16+) HLA-DR cells Regulatory T-lymphocytes (CD3+/CD25++)
Serum levels of cortisol
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
RESULTS: groups
126 enrolled women 65 women with endometriosis 61 healthy women
• Phase of menstrual cycle
Menstrual cycle
Follicular phase Luteal phase
Study group 37 (56,9%) 28 (43,1%)
Control group 33 (54,1%) 28 (45,9%)
Table 1: Groups
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
RESULTS: age
•The women were 20–46 years old
Study group 32.86 ± 6.09 years old Controls 40.49 ± 3.96 years old
(p<0,001)
Lymphocyte subpopulations (x109 cells/L)
P value
CD3+ 0,474
CD19+ 0,308
CD4+ 0,265
CD8+ 0,715
CD4/8 0,072
NK 0,060
CD3+/CD25++ 0,448
HLA-DR 0,327
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
Dejaco: Are regulatory T-cells linked with aging? (2006) Haynes:Effects of aging on T cell function (2009)
Peripheral blood lymphocyte subpopulations in follicular and luteal phase of menstrual cycle in study group (A) and control group (B)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
CD3 CD19 CD4 CD8 CD4/8 NK Treg HLA-DR
*
x10^
9 c
ells/
L
Follicular phaseLuteal phase
*
0
0.5
1
1.5
2
2.5
3
CD3 CD19 CD4 CD8 CD4/8 NK Treg HLA-DR
*
x10^
9 ce
lls /L
Follicular phaseLuteal phase
A
B
* p < 0,05
RESULTS:
p=0.005
p=0.020
p=0.045 * p < 0,05
B
p=0.005
Peripheral blood lymphocyte subpopulations in study and control group in follicular (A) and luteal (B) phase of menstrual cycle
0
0.5
1
1.5
2
2.5
3
3.5
4
CD3 CD19 CD4 CD8 CD4/8 NK Treg HLA-DR
*x1
0^9
cells
/L
Study groupControl group
*
0
0.5
1
1.5
2
2.5
3
CD3 CD19 CD4 CD8 CD4/8 NK Treg HLA-DR
*
x10^
9 ce
lls/L
Study groupControl group
A
RESULTS:
p=0.008
p=0.030 p=0.010 * p < 0,05
A
B
Regulatory T lymphocytes during the menstrual cycle in women with and without endometriosis in peripheral blood
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
Study group Control group
*
Treg
(x10
^9 c
ells
/L)
Follicular phaseLuteal phase
* p < 0,05
RESULTS:
Berbic: Regulatory T cells and other leukocytes in the pathogenesis of endometriosis (2011) Arruvito: Expansion of CD4+CD25+ and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: Implications for human reproduction (2007) Prieto: Oestradiol potentiates the suppressive function of human CD4+CD25+ regulatory T cells by promoting their proliferation (2006)
p=0.005
* p = 0.005 a
RESULTS: cortisol
•Study group: 417 ± 202 nmol/L •Control group: 341 ± 165 nmol/L (p = 0,022)
Lima: Prolactin and cortisol levels in women with endometriosis (2006)
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
RESULTS: cortisol Lymphocyte subpopulations (x109 cells/L)
Cortisol correlation coeficient
P value
CD3+ -0,126 0,159
CD19+ -0,072 0,423
CD4+ -0,125 0,164
CD8+ -0,055 0,538
CD4/8 -0,054 0,549
NK 0,051 0,574
CD3+/CD25++ -0,176 0,048
HLA-DR -0,118 0,189
Table 4: Cortisol and corrtelation with regulatory T-lymphocytes
Berne: The adrenal glands, Physiology (2004) Bradley: Differential effects of glucocorticosteroids on the functions of helper and suppressor T lymphocytes (1981)
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
CONCLUSIONS Women with endometriosis had higher
concentration of serum cortisol levels compared with healthy controls.
There was negative correlation between serum cortisol levels and regulatory T-cells concentration in peripheral blood
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
CONCLUSIONS Women with endometriosis do not exhibit
fluctuations in the concentration of cytotoxic and activated peripheral blood lymphocytes during the menstrual cycle.
A marked increase in regulatory T cell concentration in the luteal phase was detected only in endometriosis patients.
This can be attributed to altered immune response in patients with endometriosis and suggests that cytotoxic cells are not sufficiently effective.
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
CONCLUSIONS
Altered immune response has important role in pathogenesis of endometriosis.
Slabe N et al: Regulatory T-Cells in Peripheral Blood in Women with Endometriosis
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