Lukasz Wicherek

The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua

BackgroundThe presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate the subpopulations of Treg cells in conditions where a disturbance in the immunological equilibrium in ectopic endometrium and decidua has been observed, such as in cases of ovarian endometriosis (involving local immune cell suppression) and ectopic pregnancy (involving an increase in local immune system activity). We then compared these findings to what we observed in the normal eutopic endometrium of women during the secretory phase of the menstrual cycle (with immune cells under individual control).MethodsThe endometrium tissue samples evaluated in our study were obtained from 47 women during one of two kinds of laparoscopic procedures. 16 of the women underwent laparoscopies due to Fallopian tube pregnancies (EP), and 16 due to ovarian endometrioma, while 15 women made up a control group. The presence of regulatory T cells in these tissue samples was evaluated by FACS.ResultsIn our study, the percentages of FOXP3+ cells within the subpopulation of CD4+ T lymphocytes found in the decidua of the patients treated for Fallopian tube pregnancies were statistically significantly lower than both those observed in the ovarian endometriosis tissue samples and those found in the secretory eutopic endometrium samples of the control group.ConclusionThe disturbance in the immunological equilibrium observed in ectopic endometrium and decidua would seem to be related to the alteration in the Treg cell population that occurs in these ectopic tissues.

The Role of RCAS1 and Oxytocinase in Immune Tolerance during Pregnancy

Objectives: To determine and compare the level of RCAS1 (receptor-binding cancer antigen expressed in SiSo cells) in placentas at term as well as oxytocinase/cystine amino peptidase (CAP) serum level a few days before labor in order to evaluate their possible role in the regulation of maternal immune response during pregnancy and in initiation of labor. Methods: We estimated the RCAS1 content in 44 placental tissue samples, using Western blot method. We also assessed CAP serum level by its enzymatic activity, using L-cystine-di-β-naphthylamide as a synthetic substrate. The statistical analysis was performed using Shapiro-Wilk procedure. Student’s t test was applied to compare the differences between parametric data. A value of p < 0.05 was considered significant. Results: RCAS1 was found in all placental tissue samples examined. The differences in the RCAS1 relative amount depended on the onset of labor, with the highest level in induced labor and the lowest in spontaneous labor. The differences were also observed in the CAP serum level with the highest level in pregnant women whose labor was induced. Conclusions: We have observed a link between the expression of the two proteins examined and the onset of the labor. Therefore, we posit that RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor.

RCAS1 decidual immunoreactivity during placental abruption: immune cell presence and activity.

RCAS1 is a protein responsible for the suppression of cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status during placental abruption (PA) and retained placental tissue (RPT).

The Obstetrical History in Patients with Pfannenstiel Scar Endometriomas – An Analysis of 81 Patients

Introduction: The participation of immune tolerance during pregnancy was suggested to be an important factor predisposing to the implantation of decidual cells after cesarean section in Pfannenstiel scar. Delivery at term is related to the termination of immune tolerance to fetal antigens that is maintained throughout pregnancy. Substantial proportion of cesarean section deliveries is performed before the onset of true term labor. The aim of this study was to analyze the clinical symptoms of spontaneous beginning of labor in pregnant women in whom cesarean sections were performed and in whom Pfannenstiel scar endometriomas were observed during follow-up. Materials and Methods: We have retrospectively analyzed 81 patients following the surgical removal of scar endometrioma after cesarean section. Obstetrical histories of cesarean sections in the number of 5,370 preceding the occurrence of the scar endometrioma were analyzed. These data were collected in six different Gynecological and Obstetrical wards in Malopolska Province in Poland. Analysis of data was started by the retrospective evaluation of regular uterine contractions, uterine cervix ripening before cesarean section and the indications for surgery. Results: In 67 women from the group of 81 patients cesarean sections were performed with unripe uterine cervix and without the presence of regular uterine contractions. Elective indications for cesarean sections were predominant in this group of women. The relative risk of scar endometriomas occurrence following cesarean sections performed before onset of labor in comparison to cesarean sections following spontaneous onset of labor was statistically significantly higher [RR = 2.16, 95% CI = 1.21–3.83; OR = 2.18, 95% CI = 1.22–3.89]. Conclusions: Cesarean section performed before spontaneous onset of labor may increase substantially the risk of occurrence of scar endometriomas.

ORIGINAL ARTICLE: The Characterization of the Subpopulation of Suppressive B7H4+ Macrophages and the Subpopulation of CD25+ CD4+ and FOXP3+ Regulatory T-cells in Decidua during the Secretory Cycle Phase, Arias Stella Reaction, and Spontaneous Abortion – A Preliminary Report

Problem  The presence of immunosuppressive cells within the endometrium and decidua is crucial for establishing maternal immune tolerance against fetal antigens. We decided to evaluate the subpopulations of Treg cells and B7H4 macrophages in eutopic endometrium typified by Arias Stella reaction during the development of Fallopian tube pregnancy as well as in decidua at the time of spontaneous abortion (SA), and to compare these findings to those observed in the endometrium during the secretory cycle phase of healthy women.

ORIGINAL ARTICLE: The Association of RCAS1 Serum Concentration with the Reversibility or Irreversibility of the Process of Immune Cytotoxic Activity Restriction During Normal Menstrual Cycle, Cancer Relapse, and Surgical Treatment for Various Types of Squamous Cell Carcinomas and Adenocarcinomas

The selective suppression phenomenon of the cytotoxic immune response may be brought about by an increase in sRCAS1 serum concentration during the progression of cancer.

Radical hysterectomy during the transition period from traditional to nerve-sparing technique

OBJECTIVE The aim of the study was to compare peri- and postoperative data from patients operated on using the new nerve-sparing technique of radical hysterectomy with data gathered from those who underwent traditional radical hysterectomy. MATERIALS AND METHODS A total of 20 patients with cervical cancer were included in the study. The study was carried out at a time when the authors had started to perform the nerve-sparing technique by using the descriptions from the literature. During the study period 10 patients underwent the nerve-sparing procedure while the other 10 patients underwent traditional radical hysterectomy. The two groups of patients were comparable in terms of mean age, body mass index, FIGO stage, and histological type; additionally, the follow-up period was similar for both groups. RESULTS On the one hand, the mean total operative time (197.5+/-51.4 vs. 155.5+/-39.6 min) and the mean time for the hysterectomy itself (154.5+/-35.4 vs. 123.0+/-29.8 min) were significantly longer in the group operated on with nerve-sparing technique (p=0.05). Postoperatively, on the other hand, a post-void residual urine volume of less than 50 ml was noted to occur significantly faster in the patients who had undergone the nerve-sparing technique (3.5+/-1.4 vs. 9.1+/-4.2 days, p=0.00078). CONCLUSIONS Although during the introductory period nerve-sparing technique brings about an improvement in voiding function, it prolongs the total operative time in comparison to traditional radical hysterectomy.

The association between RCAS1 expression in laryngeal and pharyngeal cancer and its healthy stroma with cancer relapse

BackgroundThe purpose of this study has been to establish the level of RCAS1 – a membrane protein expressed in various cancer cells and able to induce apoptosis of CTLs and NK cells in pharyngeal and laryngeal cancer and its clear surgical margin – with respect to clinicopathological features and to patients follow up and evaluate its possible role in cancer relapse.MethodsA total of 122 tissue samples were obtained: 51 samples from laryngeal and pharyngeal squamous cell carcinoma, 51 samples from the clear surgical margins of these tumors, and 20 tissue samples derived from the healthy mucous membranes of the upper respiratory tract mucosa of patients without cancerous tumors. Patients were observed for a total of 4 years following surgical treatment. The level of RCAS1 expression was assessed by immunohistochemistry and Western blot.ResultsRCAS1 was identified in all laryngeal and pharyngeal carcinomas and in almost all the clear surgical margin samples. The level of RCAS1 expression was significantly higher in the cancerous samples than in the clear surgical margins and was determined to be related to the grade of the cancer and the presence of lymph node metastases. In cases of cancer relapse, significantly higher levels of RCAS1 expression were observed in the clear surgical margins.ConclusionSelective cytotoxic immune cell suppression concomitant with tumor growth and associated with RCAS1 expression seems to be an important event connected with cancer relapse.

Comparison of RCAS1 and metallothionein expression and the presence and activity of immune cells in human ovarian and abdominal wall endometriomas

BackgroundThe coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity.MethodsMetallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients).ResultsThe lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group.ConclusionThe expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis.

The analysis of RCAS1 and DFF-45 expression in nasal polyps with respect to immune cells infiltration

BackgroundNasal polyp constitutes a benign growth process in the nasal and sinus mucosa. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a protein expressed mainly by various human cancer cells. It is not only the marker of cancer process and its expression can also be observed in physiological processes. It is responsible for the regulation of immune cells activity. DFF45 (DNA fragmenting factor) has been described as a substrate for caspase-3. DFF45 seems to play an important role in the onset of apoptotic process by acting probably through the regulation of DNA fragmentation. The aim of the study was to evaluate the ability of nasal polyps to regulate the cytotoxic immune response and to determine their resistance to apoptosis.ResultsThe higher RCAS1 level was identified in lymphocytic nasal polyps, the medium one in eosinophilic while the lowest was identified in neutrophilic. DFF-45 expression was higher in eosinophilic than in neutrophilic and lymphocytic nasal polyps.ConclusionThe changes in DFF-45 level in nasal polyps might indicate a different resistance to apoptosis mediated by immune cells. The alterations in RCAS1 expression indicate that nasal polyps have the ability to regulate the cytotoxic immune response.The breaking of resistance to immune mediated apoptosis in nasal polyps might have a new therapeutic impact.