The expression of soluble intercellular adhesion molecule-1 in endometriosis

Objective: To investigate the association between concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and interferon-γ (IFN-γ) with regard to the severity of endometriosis.

Design: Cross-sectional study.

Setting: Infertility unit in a university hospital.

Patient(s): Seventy-one infertile patients who underwent laparoscopic evaluation were divided into two groups: 36 patients with endometriosis served as cases, and 35 patients without endometriosis served as control subjects.

Intervention(s): Peripheral blood and peritoneal fluid (PF) were collected from these patients during laparoscopic examination.

Main Outcome Measure(s): Quantitative determination of levels of human ICAM-1 and IFN-γ was performed with the use of an ELISA. The data were evaluated by Student’s t-test, analysis of variance, and regression analysis.

Result(s): Significantly elevated levels of soluble ICAM-1 were found in the sera of patients with endometriosis, especially those with advanced stages of the disease. Decreased IFN-γ levels, which were negatively correlated with serum levels of soluble ICAM-1, also were noted in the PF of patients with endometriosis.

Conclusion(s): The increased serum levels of ICAM-1 found in patients with endometriosis may indicate the presence of an active disease process. Further, the increased levels of soluble ICAM-1 in peripheral blood were inversely correlated with the concentrations of IFN-γ in PF. The increased levels of soluble ICAM-1 in plasma may be associated with an immunologic feedback response that blocks further infiltration of immune cells. These findings may be of value in the diagnosis and evaluation of endometriosis.     

子宫内膜异位症患者血清中可溶性细胞间粘附分子-1可溶性白介素Ⅱ受体23例测定及其意义

目的　测定子宫内膜异位症患者血清中可溶性细胞间粘附分子 - 1(sICAM - 1)、可溶性白细胞介素Ⅱ受体 (sIL - 2R)的水平 ,并探讨其临床意义。方法　应用酶联免疫吸附试验双抗体夹心法 (ELISA)对 2 3例子宫内膜异位症患者及 17例正常妇女血清sICAM - 1、sIL - 2R水平进行测定。结果　术前子宫内膜异位症患者血清中sICAM - 1、sIL - 2R水平明显高于正常对照组 (P <0 0 1)。轻度组与重度组之间无显著性差异 (P >0 0 5 )。血清中sICAM - 1对子宫内膜异位症的敏感性与特异性分别为 6 9 5 7%与 76 4 7%。血清sIL - 2R对子宫内膜异位症的敏感性与特异性分别为 6 5 2 2 %与 70 5 9%。血清中sICAM - 2R、sIL - 2R联合检测子宫内膜异位症的敏感性与特异性分别为 5 2 17%和 82 35 %。结论　血清中sICAM - 1、sIL - 2R可能与子宫内膜异位症的发生相关 ;检测血清中sICAM - 1与sIL - 2R有助于子宫内膜异位症的诊断和治疗     

Soluble intercellular adhesion molecule 1 in the peritoneal fluid of patients with endometriosis correlates with the extension of peritoneal implants

OBJECTIVE: To investigate the correlation of the concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) in the peritoneal fluid (PF) with the extent of peritoneal endometriotic lesions and with the presence of red lesions (RLs). STUDY DESIGN: Sixty-seven patients with endometriosis and 19 controls with normal pelvis had PF samples collected during laparoscopy. RESULTS: The concentrations of sICAM-1 in the PF of patients and controls were not different. Patients with peritoneal implant scores 4 or more had higher concentrations of sICAM-1 in the PF than those with implant scores less than 4 (P=0.018) and controls (P=0.031). No significant difference was found in sICAM-1 levels in patients with and without RLs. No correlation was detected between sICAM-1 and interleukin 1beta (IL-1beta) in either patients or controls. CONCLUSIONS: The increased concentrations of sICAM-1 in the PF of patients with greater implant scores may indicate an active shedding of the molecule from the endometriotic peritoneal tissue. No significant association was found with the presence of RLs. The levels of IL-1beta in the PF were not a relevant factor influencing the concentrations of sICAM-1.     

A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 +/- 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 +/- 145 ng/ml; n = 13; p < 0.0005 and 846 +/- 84 ng/ml; p < 0.02, respectively) compared with controls (668 +/- 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and normotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.     

Levels of soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 are increased in women with ovarian hyperstimulation syndrome

OBJECTIVE: To determine whether plasma and peritoneal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) are altered in women with ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective, case-control study. SETTING: Lis Maternity Hospital and the Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): The study group comprised 16 women with severe OHSS. The control groups comprised 10 women treated with controlled ovarian hyperstimulation and 8 women with normal findings at diagnostic laparoscopy. INTERVENTION(S): Plasma samples were obtained from the study group and the first control group. Peritoneal fluid samples were obtained during paracentesis from the study group and during diagnostic laparoscopy from the second control group. MAIN OUTCOME MEASURE(S): Samples were assayed by specific ELISA for sVCAM-1 and sICAM-1. RESULT(S): The mean peritoneal fluid levels of sVCAM-1 and sICAM-1 and the mean plasma levels of sVCAM-1 were significantly higher in the women with OHSS than in the control groups. However, the mean plasma levels of sICAM-1 were comparable. A positive correlation was demonstrated between the levels of sVCAM-1 and plasma E2 at the time of hCG administration and between the levels of sICAM-1 and number of ova retrieved. CONCLUSION(S): Our findings suggest that soluble cell adhesion molecules may have a role in the pathogenesis and progression of OHSS.     

Use of serum-soluble intercellular adhesion molecule-1 as a new marker of endometriosis

OBJECTIVE: To investigate the hypothesis that soluble intercellular adhesions molecule-1 (sICAM-1) may be used as a new serum marker of endometriosis. DESIGN: Prospective cohort study. SETTING: An academic department specializing in gynecologic laparoscopy. PATIENT(S): Consecutive series of 120 women of reproductive age who underwent laparoscopy for benign gynecologic conditions. INTERVENTION(S): Data were collected on baseline clinical characteristics, and surgical and histologic diagnosis. MAIN OUTCOME MEASURE(S): Serum concentration of both CA125 and sICAM-1. RESULT(S): Endometriosis was documented in 71 women (stage I to II in 24 cases and stage III to IV in 47 cases). Serum levels of sICAM-1 were only slightly but not significantly increased in women with endometriosis compared with women without the disease. However, serum concentration of sICAM-1 in the 21 women who were found to have deep peritoneal endometriosis was significantly enhanced when compared with both women without the disease and those with other forms of endometriosis. The sensitivity and specificity of sICAM-1 in detecting deep peritoneal endometriosis were 0.19 and 0.97, respectively; whereas those of CA125 were 0.14 and 0.92, respectively. When both parameters were used concomitantly, the sensitivity and specificity were 0.28 and 0.92, respectively. CONCLUSION(S): Although the present study tends to support a role of sICAM-1 in the development of endometriosis, serum concentrations of this molecule do not seem to be an effective indicator for the diagnosis of either the early or advanced stage of endometriosis. However, an integrated clinical and laboratory approach using both CA125 and sICAM-1 may be helpful in specifically identifying women with deep peritoneal endometriosis.     

Soluble intercellular adhesion molecule 1 in umbilical cord serum: potential for the diagnosis of neonatal infections

OBJECTIVE: To evaluate the diagnostic relevance to neonatal infections of the soluble intercellular adhesion molecule 1 (sICAM-1) cord serum level. METHODS: The case-control study included 66 term newborn infants with and without risk factors for neonatal infections. Cord blood serum determinations of white blood cell count, C-reactive protein, fibrinogen, and sICAM-1 were systematically performed associated with bacterial cultures from placenta, ears, and gastric fluids. RESULTS: 6 of 33 infants (18.2%) with risk factors were infected, and 13 (39.4%) were colonized. Two infants included in the group without infection risk factors (n = 33) were colonized. No difference in sICAM-1 cord serum levels was found according to the presence of premature rupture of membrane, fetal tachycardia >160 bpm, meconial amniotic fluid, and duration of labour >10 h. No difference in sICAM-1 was noted between infected and non-infected infants. The cord serum levels of sICAM-1 were significantly higher in infants after forceps extraction (p = 0.01). A correlation was observed between sICAM-1 and C-reactive protein cord serum levels (p = 0.004, r = 0.371) and between sICAM-1 level and neutrophil count (p = 0.01, r = 0.489). CONCLUSIONS: Our results suggest that cord serum sICAM-1 determinations have no diagnostic relevance to neonatal infection. The increase of sICAM-1 cord serum levels in infants after forceps extraction suggests its potential to evaluate cerebral trauma or hypoxia.     

Expression of intercellular adhesion molecule 1 (ICAM-1) in Plasmodium falciparum-infected placenta.

We investigated the expression of intercellular adhesion molecule 1 (ICAM-1) in malarial placenta and related histological changes. Thirty-two malarial and 40 control term placentae were collected at Tanga, Tanzania and examined histologically and immunohistochemically. Malaria infected placentae were further divided into acute (15) and chronic (17) cases according to the presence of malarial pigment. The expression of ICAM-1 on monocyte, syncytio- and cytotrophoblasts, endothelial and stromal cells was assessed. Birthweight was lower and leukocyte counts higher in placentae with chronic infection. Many monocytes were present within the intervillous spaces, especially in placentae with chronic infection, and aggregated with parasitized erythrocytes. Some monocytes were adhesive to the surface of fibrinoid deposits. ICAM-1 expression on monocytes of malarial placentae was significantly conspicuous and correlated to the degree of intervillous leukocyte infiltration. Syncytiotrophoblasts often did not show ICAM-1, even though ICAM-1 was expressed by endothelium and weakly by cytotrophoblasts and stromal cells in both infected and control placentae. These results suggest that the expression of ICAM-1 on monocytes contributes to sequestration of infected erythrocytes within the intervillous spaces and their adhesion to fibrin masses and that ICAM-1 is unlikely to be associated with the direct adhesion of infected erythrocytes to the syncytiotrophoblasts.     

Endothelium-derived nitric oxide metabolites and soluble intercellular adhesion molecule-1 in diabetic and normal pregnancies

OBJECTIVE: Endothelial dysfunction has been demonstrated in adult subjects with diabetes. We studied if maternal diabetes is associated with altered endothelial function in the fetus, as this might shed light on mechanisms by which adult diseases are programmed in utero. STUDY DESIGN: Total nitrate/nitrite (NOx) concentration was measured spectrophotometrically with the Griess reagent method. Soluble intercellular adhesion molecule-1 (sICAM-1) concentration was measured by enzyme-linked immunoassay. RESULTS: Venous cord serum NOx concentration at birth was highest in pregnancies complicated by type 1 diabetes (29.5+/-1.8 micromol/l, n=63) (P<0.0001 versus controls) and lowest in normal pregnancies (19.0+/-1.0 micromol/l, n=56). The concentration was intermediate in pregnancies complicated by gestational diabetes (23.9+/-2.7 micromol/l, n=24), but not significantly higher than in normal pregnancies (P=0.172). Venous cord serum sICAM-1 concentration did not differ between the three groups (P=0.191). Maternal serum NOx concentration in the third trimester was higher in pregnancies complicated by type 1 diabetes (22.9+/-3.4 micromol/l, n=22) than in normal pregnancies (15.4+/-1.4 micromol/l, n=21) (P=0.049). CONCLUSIONS:: Increased cord serum NOx but unaltered sICAM-1 concentration in diabetic pregnancies indicates that maternal diabetes does not cause a general alteration in fetal endothelial function. The increase in cord serum and maternal serum NOx concentration in diabetic pregnancies may be due to abnormalities in insulin-induced nitric oxide release or to a diminished reactivity of the vasculature to the effects of nitric oxide.     

Soluble tumor necrosis factor receptor II and soluble cell adhesion molecule 1 as markers of tumor necrosis factor-alpha release in preeclampsia

BACKGROUND: The purpose of this case-controlled study was to investigate whether plasma concentrations of TNF-receptors I and II and tumor necrosis factor-alpha-induced cell adhesion molecule 1 VCAM-1 could serve as more sensitive markers of tumor necrosis factor-alpha release in preeclamptic women than a direct measurement of circulating tumor necrosis factor-alpha. METHODS: Plasma concentrations of soluble tumor necrosis factor receptor I and II, immunoreactive tumor necrosis factor-a and soluble cell adhesion molecule VCAM-1 were determined in 21 patients with severe proteinuric preeclampsia (23-35 weeks' gestation) and 21 gestational age-matched normotensive controls by enzyme-linked immunoassays. Concentrations of bioactive tumor necrosis factor-alpha were assessed by the WEHI 164 bioassay. Data were statistically evaluated by Wilcoxon's rank sum and sign tests, and Spearman's test was used to evaluate clinical and biochemical correlations. RESULTS: Bioactive tumor necrosis factor-alpha was detected in 19 of 21 preeclamptic and 18 of 21 normotensive women, with no difference in plasma concentrations between both groups. Immunoreactive tumor necrosis factor-alpha, soluble TNF-receptors and soluble cell adhesion molecule VCAM-1 were significantly increased in plasma of preeclamptic patients, and a statistically significant positive correlation was observed between immunoreactive tumor necrosis factor-alpha and TNFRII. In preeclamptic patients a statistically significant negative correlation was observed between TNFRII and platelet count, and between soluble cell adhesion molecule VCAM-1 and birthweight ratio. CONCLUSION: These results show that plasma concentrations of soluble tumor necrosis factor receptor II and soluble cell adhesion molecule VCAM-1 reflect the release of tumor necrosis factor-alpha and provide sensitive markers of excessive release of this cytokine in preeclampsia.     

Endometrial immunofluorescence associated with endometriosis and pelvic inflammatory disease

Anti-immunoglobulin G (anti-IgG) staining in the endometrium by immunofluorescence has been associated with endometriosis. To investigate this phenomenon further, we took endometrial samples from 42 patients who underwent laparoscopy or laparotomy, which were tested for immunofluorescence. Fluorescein-labeled anti-IgG was incubated with tissue samples. Of 18 patients with documented endometriosis, 16 had positive immunofluorescence (89% sensitivity). Of 24 patients with no evidence of endometriosis, 9 had false-positive immunofluorescence and 15 had negative immunofluorescence. Of the 9 false-positive samples, 8 had evidence of old pelvic inflammatory disease. In the absence of this condition, there was only one false-positive study for immunofluorescence. The implications of these findings in terms of the pathophysiology of endometriosis-associated infertility is that it may be an immune-mediated process. With regard to diagnosis, the high predictive value of endometrial immunofluorescent IgG may be a useful tool in indicating early laparoscopic examination of the infertile period.     

Plasma concentration of soluble intercellular adhesion molecule-1 in women with polycystic ovary syndrome.

Soluble intercellular adhesion molecule-1 (sICAM-1) is ranked as one of the endothelial dysfunction markers and factors predicting diseases of the cardiovascular system. The main objective of this study was to assess the serum concentration of sICAM-1 in women with polycystic ovary syndrome (PCOS) and to verify correlations between serum sICAM-1 levels and selected anthropometric, metabolic and hormonal indices. The study assessed 57 women with PCOS (mean age 28.2 +/- 6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI) < or =25 kg/m2 (21 women of mean age 27.4 +/- 7.0 years) and the second with BMI >25 kg/m2 (36 women of mean age 28.6 +/- 6.0 years). In the control group there were 22 healthy women (mean age of 31.6 +/- 8.5 years). That group again was divided accordingly to BMI into two subgroups: the first with BMI <25 kg/m2 (ten women, mean age 30.2 +/- 8.4 years) and the second with BMI > 25 kg/m2 (12 women, mean age 31.7 +/- 8.7 years). The results demonstrated statistically significantly higher mean concentrations of sICAM-1 in women with PCOS as compared to healthy individuals from the whole control group and also from the control subgroup of women with BMI >25 kg/m2. There was no statistically significant difference in sICAM-1 concentration between the PCOS group and the control subgroup with BMI < or =25 kg/m2 In conclusion, higher concentrations of sICAM-1 in women with PCOS may confirm the presence of a higher risk for cardiovascular diseases in this group. Further studies are therefore necessary to identify both the factors that are responsible for the increase in sICAM-1 concentration and the clinical usefulness of routine sICAM-1 measurement in females with PCOS.     

子(癎)前期患者血中氧化低密度脂蛋白及可溶性细胞间黏附分子-1水平的变化及意义

目的探讨子癎前期(preeclampsia,PE)患者血浆中氧化低密度脂蛋白(oxidized low density lipoprotein,oxLDL)和可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)水平的变化及其意义。方法采用酶联免疫吸附法(enzyme-linked immunosorbent as-say,ELISA),检测50例PE患者[PE组,其中子癎前期轻度(mild preeclampsea,MPE)及子癎前期重度(severe preeclampsia,SPE)各25例]及25例同期正常孕妇(对照组)血浆中oxLDL和sICAM-1的水平变化。结果PE患者血浆中oxLDL和sICAM-1水平[分别为(30.56±10.29)μg/dl和(703.25±184.21)μg/L]均显著高于对照组[分别为(21.48±10.41)μg/dl和(258.07±67.45)μg/L,P均<0.01]。PE组中,SPE组oxLDL和sICAM-1的水平[分别为(33.74±9.57)μg/dl和(820.02±173.47)μg/L]均显著高于MPE组[分别为(27.39±10.18)μg/dl和(586.48±103.85)μg/L,P<0.05和<0.01]。PE组血浆oxLDL与sICAM-1的水平呈显著正相关(r=0.6175,P<0.01)。结论PE的发病与血清中oxLDL和sICAM-1的水平异常有密切关系。     

细胞间粘附分子-1在子宫内膜异位症的表达及意义

目的 探讨细胞间粘附分子-1（ICAM-1）在子宫内膜异位症发病机制中所起的作用。方法用免疫组织化学法检测子宫内膜异位症患者在位子宫内膜36例、异位子宫内膜36例及对照组子宫内膜30例ICAM-1的表达；并用酶联免疫吸附法检测子宫内膜异位症患者腹腔液47例、对照组腹腔液41例中sICAM-1的含量。结果①ICAM-1表达量的比较：子宫内膜异位症患者异位内膜〉对照组内膜〉子宫内膜异位症患者在位内膜；②子宫内膜异位症患者腹腔液sICAM-1含量明显高于对照组，P=0．0078；③Ⅰ，Ⅱ期和Ⅲ～Ⅳ期子宫内膜异位症患者腹腔液sICAM-1含量无明显差异，P=0．37。结论 ICAM-1的异常表达在子宫内膜异位症发病过程中起一定作用。     

Endometrial biology and the etiology of endometriosis

Two recent studies reported in this issue of Fertility and Sterility have explored important issues regarding the understanding and diagnosing of endometriosis. These studies emphasize the complexity of endometriosis and underscore the different roles of clinicians and translational scientists in exploring this disease.     

Aberrant expression of intercellular adhesion molecule-1 and killer inhibitory receptors induces immune tolerance in women with pelvic endometriosis

OBJECTIVE: To investigate host immunologic response to endometriosis in terms of intercellular adhesion molecule (ICAM)-1 expression by macrophages and killer cell inhibitory receptor (KIR) expression by natural killer (NK) cells. DESIGN: Case-control study of immunologic markers. SETTING: University hospital. PATIENT(S): Twenty-eight Japanese women with endometriosis. Control subjects were 26 women without endometriosis. Diagnoses were made at laparoscopy. INTERVENTION(S): Venipuncture and laparoscopic peritoneal fluid collection. MAIN OUTCOME MEASURE(s): ICAM-1 expression by macrophages and KIR expression by NK cells, measured by flow cytometry. RESULT(S): In women with endometriosis, expression of ICAM-1 by peritoneal macrophages was significantly lower and expression of KIR by NK cells in peritoneal fluid and peripheral blood was significantly higher than in control subjects. CONCLUSION(S): Properties of macrophages and NK cells in women with endometriosis promote immunotolerance to implanted tissue in the peritoneal environment. Increased KIR(+)NK cells in peripheral blood may represent a risk factor for endometriosis.     

The relationship between the level of expression of intercellular adhesion molecule-1 in placenta and onset of preeclampsia

OBJECTIVE: To investigate the differences in the expression of intercellular adhesion molecule-1 (ICAM-1) in the placenta and the concentration of soluble ICAM-1 between early-onset and late-onset preeclampsia. METHODS: Preeclampsia was divided into early-onset type (EO: 20 to 31 weeks gestation) and late-onset type (LO: > or = 32 weeks gestation). Post delivery, placentas were obtained from 19 control pregnant women and from 9 EO and 8 LO preeclamptic women. The expression of ICAM-1 in placenta was determined by immunohistochemical staining. Blood samples were taken from 21 non-pregnant women, 16 control pregnant women, 13 EO and 8 LO preeclamptic women, and umbilical cord blood samples from 38 control pregnancies and from 16 EO and 14 LO preeclampsia. The concentration of ICAM-1 was measured by enzyme-linked immunosorbent assays. RESULTS: The expression of ICAM-1 in placenta was higher in LO than in EO preeclampsia (48.2 +/- 8.2% vs 17.9 +/- 5.0%) (p < 0.05). ICAM-1 concentration in umbilical cord blood was higher in EO than in LO preeclampsia (umbilical artery, 150.6 +/- 34.0 ng/ml vs 90.3 +/- 9.4 ng/ ml) (umbilical vein, 128.3 +/- 31.2 ng/ml vs 91.3 +/- 10.2 ng/ml) (p < 0.05). CONCLUSIONS: Significant differences were noted in the expression of ICAM-1 between patients with EO and LO preeclampsia, which suggest that the possibility that EO and LO preeclampsia may have different onset mechanisms.     

Soluble intercellular adhesion molecule and C-reactive protein as early markers of infection in newborns

In order to find a reliable early marker of infection in newborns a study with simultaneous determination of soluble Intercellular Adhesion Molecule-1 (sICAM-1) and C-Reactive Protein (CRP) was planned. Prospectively 90 babies < 5 days of age suspect of infection were included. Retrospectively this population was classified into an "infected" group (n = 45) and a "non-infected" group (n = 45). For each of these two groups we calculated the sensitivity, specificity and predictive values of sICAM-1 and CRP as early markers of infection. We determined the best cut-off level for sICAM-1 to be 300 micrograms/l and for CRP 5 mg/l. As a biochemical test for infection in the newborns the sensitivity and negative predictive value for CRP were 0.69 and 0.73 respectively. When sICAM-1 was added and CRP and s-ICAM-1 were used in combination the sensitivity improved significantly to 0.93, p < 0.01 and the negative predictive value improved to 0.92, p < 0.05. In normal 5-8 days old babies' sICAM-1 was significantly higher than at birth (cord blood), p < 0.0001. In conclusion, sICAM-1 and CRP in combination are better than CRP as a primary test for identification of infection in babies < 5 days of age.