REGULATORY T CELLS in PERIPHERAL BLOOD in · PDF filewomen with OVARIAN and PERITONEAL ENDOMETRIOSIS Nina Slabe, MD, PhD ... Ribič-Pucelj: Globoka infiltrativna endometrioza (2007)

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)


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


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


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


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


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


*

x10^

9 ce

lls /L


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


*x1

0^9

cells

/L

Study groupControl group

*

0

0.5

1

1.5

2

2.5

3


*

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)


* 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)


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)


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


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.


CONCLUSIONS

Altered immune response has important role in pathogenesis of endometriosis.


Thank you for listening.

Documents

REGULATORY T CELLS in PERIPHERAL BLOOD in · PDF filewomen with OVARIAN and PERITONEAL ENDOMETRIOSIS Nina Slabe, MD, PhD ... Ribič-Pucelj: Globoka infiltrativna endometrioza (2007)