sIL-2R Expression Research Articles

Expression of SIL-2R in Patients with Multiple Myeloma and Its Clinical Significance

To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM). 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and β2-microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed. The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group (P<0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients (P=0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of β2-microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells(P>0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference (P=0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group (P=0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis. The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.

Modulation of Soluble Interleukin 2 Receptor (sIL-2R) Levels in Patients with HIVWaldenstrom Macroglobulinemia (HIV-WM) Treated with Biaxin-Pentoxifylline-Dexamethasone Followed by Prednisolone (BPD-Pred)

Serum levels of sIL-2R represents the total amount of activated T-lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organ sites. Most malignant diseases overexpress sIL-2R in comparison to non-malignant controls. Immunomodulatory effect of IL-2 therapy on interferon (IFN), tumor necrosis factor alpha (TNF-a) production, nuclear factor kappa–b (NFkb) in vivo and in vitro and on the expression of sIL-2R in Human Immunodeficiency Virus – Waldenstrom Macroglobulinemia (HIV-WM) patients with IgM is not well defined. We present a 42 year old female with HIV, CD4-343/cu mm, viral load (VL) of >100K (persistently elevated VL), hypercoagulable state, serum viscosity >3 centpoises, IgM level of >1 gram with serum free light chain kappa/lambda ratio elevated as well as IgG and IgA on immunofixation studies. She was treated initially with BPD (Biaxin, Pentoxifylline, Dexamethasone) with partial response and with poor paraprotein parameter response. Her HAART regimen consisted of ritonavir base therapy. When dexamethasone was weaned off and prednisolone therapy started, greater than 50% reduction of paraprotein (IgM) occurred over 4–6 weeks. We measued serum sIL-2R, C-reactive protein (CRP), throughout treatment over 12 weeks. The serum sIL-2R level significantly decreased from 21,513.274 pg/ml to 5,424.779 pg/ml (normal 3,592.9 – 9,734.5 pg/ml). The C-reactive protein normalized and IgM was now 0.211 gram and within normal limits as well as serum viscosity.CONCLUSIONS: The suppression and modulation therapy of CRP gene transcription with manipulation of NFkb/IKKb with ritonavir based HAART and BPD-Pred with normalization of sIL-2R, CRP, and IgM paraprotein in HIV-WM patients may have an independent effect on prognosis and maintenance therapy. Serum sIL-2R levels may serve as a useful marker in evaluating HIV-WM disease, stage for stage and monitoring disease progression.

Expression of sIL-2R before and after chemotherapy in patients with breast cancer

To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients, and evaluate the clinical value of the sIL-2R in breast cancer’s diagnosis and therapy. The peripheral blood sIL-2R levels of the breast cancer patients with or without chemotherapy were detected by ELISA. The healthy persons were made as the control group. The sIL-2R levels of the breast cancer patients were higher than that of the control group(P 0.05). The breast cancer patients have the high sIL-2R levels. There is a close relationship between the cancer incidence and the patients, immune situation. The level of sIL-2R could be a clinical index which can be used for evaluating the cancer degree, because the higher levels of sIL-2R can indicate that the immune ability of patient is worse. There is a significant difference between the sIL-2R levels of the patients before chemotherapy and that of the patients undergone chemotherapy.

T cell immune response is correlated with fibrosis and inflammatory activity in hepatitis B cirrhotics

To explore the relationship among interferon-gamma (IFN-gamma) activity, fibrogenesis, T cell immune responses and hepatic inflammatory activity. Peripheral blood samples from a total of 43 hepatitis B cirrhotic patients (LC) and 19 healthy controls (NC) were collected to measure their serum levels of IFN-gamma, interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-10 (IL-10) and three serological markers of fibrosis including hyaluronic acid (HA), procollagen type III peptide (PIIIP), and type IV collagen were measured using a double antibody sandwich ELISA. Also, serum total bilirubin (TB) and alanine aminotransferase (ALT) were measured by routine measures. The concentrations of serological markers of fibrosis in patients with active cirrhosis (ALC) were significantly higher than those in stationary liver cirrhosis (SLC) or NC groups. The levels of serological markers in HBeAg-positive patients were significantly higher than those in HBeAg-negative patients. In SLC and ALC patients, a negative linear correlation was found between IFN-gamma levels and the serological markers of fibrosis. IFN-gamma and IL-2 levels in the ALC group were significantly higher than those in the SLC and NC groups, but the statistical difference was not significant between the latter two. In contrast, IL-10 levels in the SLC group were significantly higher than that in the NC group, but no significant difference was found between SLC and ALC groups. The sIL-2R level was elevated gradually in all these groups, and the differences were significant. Positive linear correlations were seen between IFN-gamma activity and ALT levels (r = 0.339, P < 0.05), and IL-2 activity and TB levels (r = 0.517, P < 0.05). sIL-2R expression was positively correlated with both ALT and TB levels (r = 0.324, 0.455, P < 0.05), whereas there was no statistically significant correlation between IL-10 expression and serum ALT and TB levels (r = -0.102, -0.093, P > 0.05). Finally, there was a positive correlation between IFN-gamma and IL-2 levels. T cell immune responses are correlated with fibrosis and hepatic inflammatory activity and may play an important role in liver cirrhosis.

Immunomodulation therapy and soluble interleukin-2 receptor (sIL-2R) levels in patients with HIV- myeloma (HIV-M, triclonal gammopathy) treated with biaxin-pentoxifylline-decadron (BPD)

6739 Background: Levels of serum sIL-2R represents the total amount of activated T lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organs. In most malignant diseases, elevated levels of serum sIL-2R are present, compare to normal control. Immunomodulatory effect of low dose IL-2 therapy on interferon (IFN), tumor necrosis factor (TNF) production in vivo and in vitro and on the expression of sIL-2R in HIV-M patients with IgM-laden myeloma cells and triclonal is unknown. Methods: We present a 63 year old female with stage II multiple myeloma (HIV-M), referred to our center with epistaxis, hypercoagulabe state, protein S deficiency, lupus anticoagulant and severe gastrointestinal distress (angulated transverse colon) and a serum viscosity of > 3.00 centipoises (cp). She was treated with immunomodulation therapy BPD (Biaxin, Pentoxifylline, Decadron). Prior to admission she was given plasmapheresis once but relapsed soon afterwards with a rising serum viscosity and bleeding. Her paraprotein parameters were reduced by 50% over ten weeks. We measured serum sIL-2R, C-rective protein (CRP), beta-2-microglobulin (B2M), IgG-kappa, IgG-lambda, IgM-kappa, before and throughout immunomodulation therapy. Her CD4+ count: 728/cumm: viral load:>100K. Highly antiretroviral therapy (HAART) was started. Results: The CRP level began decreasing with cessation of epistaxis. Triclonal parameters decreased steadily over 12 -24 weeks. The sIL-2R level was significantly reduced to normal levels after 24 weeks of immunomodlulation therapy but the beta-2- microglobulin levels remained elevated. Conclusions: The suppression with immunomodulation therapy of CRP gene transcription with manipulation of NF-Kb and IK-Kb with BPD and normalization of sIL-2R in HIV-M patients with early stage triclonal myeloma may have a direct independent effect on the prognostic factor in triclonal IgM-laden HIV-M patients. Serum sIL-2R levels may be a useful parameter for evaluating HIV-M disease stage and monitoring the disease progression during and post-treatment follow-up. No significant financial relationships to disclose.

Levels of soluble interleukin-2 receptor in the sera and skin tissue fluids of patients with vitiligo

In order to study the possible role of soluble interleukin-2 receptor (sIL-2R) in the pathogenesis of vitiligo, we measured the levels of sIL-2R in the sera and the tissue fluids from skin lesions and uninvolved skin from 41 patients with vitiligo, using the method of sandwich ELISA with monoclonal and polyclonal antibodies. The results showed that the overall level of serum sIL-2R from patients with vitiligo was significantly higher than that from normal control group ( P<0.01).The serum level of sIL-2R in both generalized and focal types was significantly higher than that in normal control group ( P<0.01), but there was no significant difference between the segmental type and normal control group ( P>0.05). The level of serum sIL-2R from patients with vitiligo in progressive stage was significantly higher than that in stable stage ( P<0.0l). The level of sIL-2R in the tissue fluid from the skin lesion of the patient was significantly higher than uninvolved skin of the same patient ( P<0.05). The above data indicate that there is an association between the expression of sIL-2R and the pathogenesis of vitiligo. The level of serum sIL-2R in vitiligo is related to the activity of the disease, therefore the measurement of it may be significant in estimating the severity and the prognosis of the disease.

Cytokine profile during high‐dose rhG‐CSF therapy in severe congenital neutropenia

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytokine profile was evaluated in a case of severe congenital neutropenia. The plasma levels of cytokines were measured before and during rhG-CSF therapy. These included G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha, interleukin-1 beta, interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Soluble interleukin-2 receptor (sIL-2R) was measured serially during rhG-CSF therapy. Lymphocyte subpopulations including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were also measured, rhG-CSF was administered once daily as a 30-min infusion. The patient was treated with increasing dose levels of 100, 200, 400, 800, and 1,600 micrograms/m2/day. The level of endogenous G-CSF was elevated to 334 pg/ml before treatment and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. Clinically, he showed a moderate response to a high dose of rhG-CSF (1,600 micrograms/m2/day). Plasma levels of G-CSF markedly increased during therapy but plasma levels of other cytokines did not show significant changes during therapy and lymphocyte subpopulations did not significantly change. A drastic increase in sIL-2R expression was observed after rhG-CSF infusion and an increase in sIL-2R expression occurred even before a major increase in granulocyte counts. These results showed that a high dose rhG-CSF therapy may influence the cytokine network as judged by the increased sIL-2R expression.

Detection of soluble IL‐2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM‐CSF

Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) expression with a cell-free enzyme-linked immunosorbent assay (ELISA) system (T-Cell Sciences; Cambridge, U.S.A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA), 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL-2R levels between RA (median 368 U/ml). RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected. Six patients, who had been under treatment with rhGM-CSF for at least 2 weeks, demonstrated a three- to sevenfold increase of sIL-2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL-2R expression begins within 4 h after subcutaneous application of GM-CSF and reaches its maximum after 12 h. Our data cannot suggest whether increased sIL-2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM-CSF in MDS may result in improvement of altered lymphocyte function. As GM-CSF induces sIL-2R expression, a down regulation of the immune response caused by neutralization of free IL-2 cannot be excluded.