Immunosuppressive Acidic Protein Values Research Articles

Prognostic Value of Immunosuppressive Acidic Protein and Oxidative Stress Status in Critically Ill Patients.

IntroductionThe aim of this study was to determine the prognostic value of admission immunosuppressive acidic protein (IAP), interleukin-6 (IL-6), total oxidant status (TOS), and total antioxidant status (TAS) in 161 critically ill patients.Materials and methodsThis prospective observational study was carried out in the Emergency Department ICU for 6 months. Critically ill patients were included in the study consecutively. The main outcomes were the need for early mechanical ventilation (MV) and in-hospital mortality.ResultsThe mean age of 161 patients was 66.5 ± 17.1 years. The median IL-6 levels of patients who required early MV were significantly higher than of the patients who required no MV (p < 0.001), and the median IL-6 levels in the nonsurvivors were significantly higher than in the survivors (p < 0.001). The median IAP levels were not significantly different between the groups (p = 0.464 for early MV and p = 0.340 for the in-hospital mortality group). The AUCs of IL-6 and TOS for predicting in-hospital mortality were 0.819 and 0.608, respectively.ConclusionThe IAP level on admission to ICU is ineffective in predicting the need for early MV and in-hospital mortality; however, IL-6 level on admission is a strong prognostic predictor in critically ill patients. Our findings showed that the burden of oxidative stress was high in general ICU patients.Clinical significanceOur study showed that increased oxidative stress is an important problem in critically ill patients. If measures are taken to reduce oxidative stress by physicians, the prognosis of critically ill patients will be better.How to cite this articleTutuncu EO, Dundar ZD, Kilinc I, Tutuncu A, Kocak S, Girisgin AS. Prognostic Value of Immunosuppressive Acidic Protein and Oxidative Stress Status in Critically Ill Patients. Indian J Crit Care Med 2021;25(4):405–410.

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Neutrophil Elastase Inhibitor (Sivelestat) Preserves Antitumor Immunity and Reduces the Inflammatory Mediators Associated with Major Surgery

To examine the effects of the administration of perioperative sivelestat, a selective neutrophil elastase inhibitor, on tumor immunity and inflammatory mediators in patients who undergo major surgery. Thirteen patients admitted to the hospital for elective surgery were equally randomized into one of two groups: the Sivelestat group (n = 6) and the control group (n = 7). Thereafter, the immunosuppressive acidic protein (IAP), serum interleukin-6 (IL-6), and type 1/type 2 T-helper cell balance were all assessed at several time points before and after surgical intervention. The serum IL-6 values at 1 and 12 h after surgery and on postoperative days 1 and 3 were all significantly lower in the sivelestat group than in the control group. The IAP values at postoperative days 7 and 28 in the sivelestat group were also significantly lower than those in the control group. There was a significant correlation between the IL-6 level at 1 h after surgery and the IAP level at postoperative days 7 and 28. In this preliminary study, the perioperative administration of sivelestat was thus suggested to reduce surgical stress by decreasing the cytokine release and preserving the antitumor immunity.

Beneficial effects of protein-bound polysaccharide K plus tegafur/uracil in patients with stage II or III colorectal cancer: Analysis of immunological parameters

Protein-bound polysaccharide K (PSK) increased the 5-year disease-free survival rate and reduced the risk of recurrence in a randomised, controlled study for stage II and III colorectal cancer. In order to elucidate the disease-free survival benefits with PSK and what immunological markers could indicate a PSK responder, serial changes in immunological parameters were monitored in the study. PSK decreased the mean serum immunosuppressive acidic protein (IAP) level, and increased the mean population of natural killer (NK) cells compared with the controls. The 5-year disease-free and overall survival rate for patients with serum IAP values <or=500 microg ml(-1), which represents the normal value, were 75.5% (95% CI: 66.8-84.2%; p=0.016) and 85.1% (95% CI: 77.9-92.3%; p=0.032), respectively, in the PSK group compared with 57.5% (95% CI: 43.3-71.6%) and 70.2% (95% CI: 57.1-83.3%) in the control group. In patients with NK cell population >or=8% at 3 months after surgery, PSK conferred a significantly better (p=0.038) 5-year disease-free survival (86.7%; 95% CI: 74.5-98.8%) compared to the control group (60.0%; 95% CI: 29.6-90.4%). In the proportional hazards model, the presence of regional metastases (relative risk, 3.595; 95% CI: 1.518 to 8.518; p=0.004) and omission of PSK treatment (relative risk, 3.099; 95% CI: 1.202 to 7.990; p=0.019) were significant indicators of recurrence. PSK acts as an immunomodulatory activity and biochemical modulator in stage II or III colorectal cancer. Pre-operative serum IAP values <or=500 microg ml(-1) and an NK cell population >or=8% at 3 months after surgery are possible PSK response predictors.

Prognostic value of serum immunosuppressive acidic protein in renal cell carcinoma

To determine whether the immunosuppressive acidic protein (IAP) could be a useful marker for renal cell carcinoma (RCC), serum IAP levels were compared with clinicopathological features in RCC patients. Furthermore, IAP cutoff level to predict the recurrence was determined using receiver operating characteristics (ROC) curve analysis. Between January 1994 and December 1998, pretreatment serum IAP was measured in 123 consecutive patients with PCC at Kitasato University Hospital. Ninety-eight patients were received radical surgery and 86 patients were performed as clinically curable renal cell carcinoma (pT1-pT3N0M0). ROC curve analysis was utilized to set the cutoff value of IAP for prediction of cancer recurrence. Significance of prognostic factors in RCC recurrence was analyzed by Cox proportional hazard model. The mean age of the 123 patients was 58.6 years (range 33 to 90, median 59). The mean follow-up period was 24.8 months (range 1 to 78, median 26). The median IAP levels were 447 ug/ml in stage I, 629 ug/ml in stage II, 588 ug/ml in stage III and 1,150 ug/ml in stage IV (p < 0.05). Tumor size and venous involvement were significantly associated with IAP concentrations (p < 0.05). However, tumor grade did not correlate with IAP level. Of 86 patients with clinically curable tumor, 79 patients were disease-free after median follow-up of 27 months. Using ROC curve analysis, IAP cutoff level for prediction of cancer recurrence was set at 620 ug/ml. Disease-free survival rate in patients with preoperative IAP levels of 620 ug/ml or lower was 98.5% (67/68) at 27 months postoperatively, whereas that in patients with IAP greater than 620 ug/ml was 75.0% (12/18). This difference was statistically significant (p < 0.05). Results of multivariate analysis revealed that preoperative IAP and pT stage were statistically significant factors for tumor recurrence after radical surgery (p < 0.05). The present study indicates that preoperative IAP level is a useful prognostic marker in patients with RCC. In particular, patients with clinically curable tumors (pT1-3N0M0), whose preoperative IAP levels greater then 620 ug/ml may have high risk for recurrence after radical nephrectomy.

Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: Covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system

The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox's proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 microg/ml) with predicted negative antitumor immune reactions, splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.

Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma: Findings from three independent clinical trials

Immunosuppressive acidic protein (IAP) has been reported to have close correlation with the impairment of host immune response. To evaluate the significance of IAP in clinical studies, the prognostic value of preoperative IAP was investigated in clinical trials of patients with gastric carcinoma after curative resection. An appropriate IAP threshold value of 580 micrograms/mL was determined using Cox's proportional hazards model. Five-year survival rates were estimated for high and low IAP groups in three different clinical studies. Meta-analysis was performed based on individual patient data, and summarized hazard ratios were estimated using a stratified proportional hazards model. Meta-analysis of the three clinical trials demonstrated that patients with preoperative IAP levels above the threshold had significantly poorer cancer related survival (P = 0.0039) and absolute survival (P = 0.0023), even after adjustment for the major prognostic factors. Gastric carcinoma patients with an IAP value above the threshold level of 580 micrograms/mL have a higher risk of cancer death and absolute death than patients with an IAP value below the threshold value.

Immunosuppressive Acidic Protein in Patients with Lung Cancer

Using a single radial immunodiffusion method, serum immunosuppressive acidic protein (IAP) was determined in 117 patients with primary lung cancer, 34 patients with benign lung disease, and 45 healthy control subjects. The mean value of IAP for patients with lung cancer was significantly higher than that of normal control subjects. There were no significant differences in IAP levels among different histologic types and among different stages of lung cancer. It was concluded that serum IAP level was elevated in patients with lung cancer, especially during the early postoperative period, and serial measurements of serum IAP were of value in monitoring lung cancer patients.

The Influence of Immunosuppressive Acidic Protein on the Activity of Peripheral K-Lymphocytes in Subacute Thyroiditis

We previously reported that immunosuppressive acidic protein (IAP), an alpha 1-acid glycoprotein, is increased during the acute phase of subacute thyroiditis (SAT). In this study we measured the percentage and absolute number of peripheral K-cells using a plaque-forming cell technique to investigate immunological abnormalities associated with SAT. Additionally, we investigated the relationship between IAP and peripheral K-cell activity. In normal controls, a sex-related difference in the percentage of K-cells among total lymphocytes was present; the percentage was significantly lower in women (mean +/- SD, 5.0 +/- 2.0%; n = 12; P less than 0.01) than in men (8.4 +/- 2.9%; n = 13). However, there was no difference (0.153 +/- 0.073 x 10(9)/L in five females; 0.173 +/- 0.054 x 10(9)/L in seven males) in the absolute number of peripheral K-cells. During the acute phase of SAT, the percentage (2.4 +/- 1.9% in 16 females; 2.7 +/- 1.0% in 3 males) and absolute number (0.058 +/- 0.048 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls. These values returned to normal during the recovery phase, although their mean values were still lower than those in normal controls. In female patients with Graves' disease, the percentage (2.2 +/- 1.8% in 11 females) and absolute number (0.038 +/- 0.033 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls; in male patients, the percentage (4.2 +/- 2.7% in 5 males) was lower than that in normal controls, but the absolute number (0.136 +/- 0.114 x 10(9)/L) of K-cells was not significantly different. Serum IAP values during the acute phase of SAT showed a significant negative correlation with the percentage of K-cells (r = -0.66; P less than 0.01). The number of K-cells from a normal subject decreased significantly when these lymphocytes were incubated with sera from patients with SAT, and the mean inhibition rate of K-cells by serum samples from 13 SAT patients during the acute phase was higher than that during the recovery phase (68.0 +/- 21.0 vs. 38.0 +/- 23.0%; P less than 0.01). Purified IAP inhibited the activity of K-cells from normal subjects dose dependently. These results suggest that 1) there may be inhibitory factors for the antibody-dependent cell-mediated cytotoxicity of peripheral K-cells in the serum of patients with SAT, and 2) IAP may be one of these inhibitory factors.

整形外科疾患における血清免疫抑制酸性蛋白の測定

We evaluated an Immunosuppressive acidic protein (IAP) in 240 cases of a disease of bone and joint. The IAP positive rate of a primary malignant tumor of bone was 60% and the mean was 591μg/ml. This rate of metastatic bone tumor was 67% and the mean was 578μg/ml. This rate of a benign tumor of bone was 10% and the mean was 382μg/ml. IAP may represent a tumor marker in malignant tumors of bone like carcinoma in other organ. The IAP positive rate of RA was 80% and the mean was 704μg/ml. All of the cases of gout had abnormal high value of IAP on attack. All of the cases of OA had normal value.

Significant increase in immunosuppressive acidic protein (IAP) in serum of patients with multiple sclerosis and other inflammatory neurological disorders

IAP, a type of α 1-acid glycoprotein, is mainly produced by macrophages when stimulated in the presence of circulating immune complexes or some inflammatory substances. We assayed the serum levels of IAP by a single radial immunodiffusion method. The normal level of IAP is below 500 μg/ml (385 ± 73). In multiple sclerosis patients, however, IAP increased during exacerbation (630 ± 191) and decreased during the inactive stage (433 ± 170). Eighty-five percent of patients with neuro-Behçet's disease also had high levels of IAP, correlating well with disease activity. In some patients with Guillain-Barré syndrome or Miller Fisher syndrome, IAP increased during the acute phase. In patients with herpes simplex encephalitis, IAP levels remained abnormally high for more than 60 days after onset. The mean value of IAP in patients with amyotrophic lateral sclerosis did not differ from that of normal controls. An increase in IAP in the serum of patients seems to reflect the activity of an inflammatory or immunopathological process.

Serum immunosuppressive acidic protein in renal cell carcinoma.

Serum immunosuppressive acidic protein (IAP) was determined in 45 patients with renal cell carcinoma (20 preoperative and 25 postoperative) and 12 healthy adults. The mean values of serum IAP in patients with renal cell carcinoma of low stage (566.3 +/- 197.7 micrograms/ml) and high stage (936.9 +/- 208.8 micrograms/ml) were statistically higher than those of controls (368.8 +/- 84.5 micrograms/ml). Positive rate of IAP levels was found in 58.3% and 100% of patients with low stage and high stage, respectively. The mean value of serum IAP was 756.4 +/- 361.0 micrograms/ml in patients with metastases, while patients without metastases had a value of 434.7 +/- 170.9 micrograms/ml. There was a statistically significant difference between the two populations. These results suggest that IAP levels appear to provide a useful diagnostic and follow-up marker in renal cell carcinoma patients.

Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL).

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.

Serum Immunosuppressive Acidic Protein (IAP) In Patients with Malignant Head and Neck Tumors

Measurements were carried out on the serum immunosuppressive acidic protein (IAP) level of patients with malignant head and neck tumors. The serum IAP value in patients with malignancies was significantly higher than that in healthy subjects and those with benign tumors. Following treatment, in cases with favorable progress the high IAP values prior to treatment showed a decline, becoming normal. Whereas in cases showing poor progress, there was a delay in reverting to normal values and some were observed to retain the same high values.

The relationship between serum IAP and peripheral K cells in patients with subacute thyroiditis

In a previous study, we showed that the percentage of peripheral K cells of patients with subacute thyroiditis (SAT), determined by a plaque-forming cell technique, was significantly lower than that of normal controls, and that ther sera from SAT significantly inhibited the activity of K cells in normal lymphocytes, suggesting that in the sera of SAT there is some factor which inhibits K cell activity. In this study, we investigated the relationship between K cells and the serum immunosuppressive acidic protein (IAP), the sex difference in percentage of K cells, and the absolute count of K cells in patients with SAT. In normal controls, there was a sex difference in the percentage of K cells in total lymphocytes; the percentage was significantly lower in women (mean +/- S.D., 5.0 +/- 2.0%; n = 12; p less than 0.01) than in men (8.4 +/- 2.9%; n = 20). However, there was no sex difference in the absolute count of peripheral K cells. In the acute phase of SAT, the percentages of K cells wee 2.4 +/- 1.8%; 2.4 +/- 1.9% and 2.7 +/- 1.0% in 19 patients, 16 females and 3 males, respectively, which were significantly lower than 6.8 +/- 3.0%, 5.0 +/- 2.0% and 8.4 +/- 2.9% in 25 controls, 12 females and 13 males, respectively. The absolute counts of K cells in the acute phase of SAT were 56 +/- 45/mm3 and 58 +/- 48/mm3 in 13 patients including 11 females, respectively, which were significantly lower than 165 +/- 63/mm3 and 153 +/- 73/mm3 in 12 patients including 5 female controls, respectively. It was observed that serum IAP values in SAT were correlated negatively with the percentage of K cells and positively with the inhibition rate of SAT sera on K cells from normal subjects. Moreover, purified IAP showed a dose-related inhibition on the K cells from the control subjects. These results suggest that IAP in the sera of SAT seems to be one of the factors which inhibits the activity of K cells.

頭けい部悪性しゅようにおける血清ＩＡＰ（Ｉｍｍｕｎｏｓｕｐｐｒｅｓｓｉｖｅ Ａｃｉｄｉｃ Ｐｒｏｔｅｉｎ）値の臨床的意義

Immunosuppressive Acidic Protein (IAP) in the serum of 58 patients with malignant tumor and 13 normal individuals was quantitatively determined by single radial immunodiffusion. The IAP values in 46 epidermoid carcinomas and 12 malignant lymphomas ranged from 697.4+350.8μg/ml to 829.0+372.0μg/ml, significantly higher than those of normal individuals (389.2+93.1μg/ml). The upper limit of normal is usually considered to be 500μg/ml. The IAP value rises as the clinical stage of the tumor advances.Actually, the highest value of IAP in stage IV patients was 888.2μg/ml, and 81.8% of the patients had IAP values above 500μg/ml. An additional experiment showed that natural killer activity of lymphocytes from the patients with malignant tumors correlated well the IAP levels.It is concluded that IAP values not only reflect the immune state of tumor patients, but also are very useful in clinical diagnosis.

Evaluation of serum immunosuppressive acidic protein (IAP) in patients with malignant disease

IAP is one of serum immunosuppressive factors in patients with malignant disease. We evaluated correlation between serum IAP values and other immunological parameters and histopathological findings in patients with malignant disease, especially gastric cancer and lung cancer.IAP values showed negative correlation with PPD and SU-PS skin tests in patients with gastric cancer and correlated with alpha 1-and alpha 2-globlin in patients with gastric cancer and lung cancer.IAP values also increased mostly in accordance with advances of the disease in patients with gastric cancer and lung cancer. In patients with gastric cancer, IAP values correlated with size of the tumor and showed significant difference between group with lymphnode metastasis and those without metastasis.These results suggested that IAP was useful to evaluate immunological state and advance of the disease in patients with malignant disease.However, IAP is not specific for malignant disease, since it is also closely related to inflammation.

Immunosuppressive acidic protein in patients with ovarian cancer

Serum immunosuppressive acidic protein (IAP) was determined in 63 patients with ovarian tumors (33 benign and 30 malignant) and 79 healthy female controls, and was examined as a marker for ovarian cancer in comparison with carcinoembryonic antigen (CEA). The mean value of serum IAP in patients with ovarian cancer (1085 +/- 474 micrograms/ml) was statistically higher than those of both benign tumors (394 +/- 93 micrograms/ml) and controls (298 +/- 92 micrograms/ml). Elevated levels of IAP and CEA were found in 93.3% and 30.0% of patients with ovarian cancer, respectively. There were three false-positive cases with IAP and two with CEA. Elevation of IAP was recognized in all cancer patients in Stage I, whereas 33.3% of these patients showed elevated CEA. The occurrence of elevated serum IAP was not affected by tumor histologic features. Serial IAP determination appeared to provide a useful follow-up marker in patients in whom CEA was low in value. The measurement of serum IAP is highly recommended as an addition to the conventional diagnostic methods.

Immunosuppressive acidic protein (IAP) in gastric cancer patients.

Immunosuppressive acidic protein (IAP) in the serum from peripheral, splenic and regional venous blood of gastric cancer patients was assayed. Peripheral venous blood was collected before, and for several months after the surgery. The IAP values of peripheral venous blood, increased with advancing cancer stage; in patients at the same cancer stage, the IAP values of venous blood draining from the cancer lesion were the highest. In curatively operated patients, the IAP values increased during the first postoperative month and decreased thereafter. In patients with non-resectable cancer and in patients subjected to palliative surgery, these values remained high; they increased sharply just before death. Determination of the serum IAP values in gastric cancer patients may be useful in estimating the immunological state of gastric cancer patients and for monitoring the postoperative immunological status.