[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes]. / Neopterin a solubilní receptor interleukinu-2 u nemocných se systémovým lupus erythematodes.

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.

[Relation of serum levels of the soluble cytoadhesion molecules sVCAM-1 and sICAM-1 to selected factors in the cytokine network in multiple myeloma]. / Vztah hladin solubilních cytoadhezivních molekul sVCAM-1 a sICAM-1 v séru k vybraným pusobkum cytokinové síte u mnohocetného myelomu.

BACKGROUND: Contemporary, not very frequent studies have brought only few and often inconsistent findings about the significance of cytoadhesive molecules (CAM) type "vascular cell adhesion molecule-1" (VCAM-1) and "intercellular cell adhesion molecule-1" (ICAM-1) at multiple myeloma (MM). The aim of the study was to interpret relations among levels of soluble forms of VCAM-1 and ICAM-1 in serum of the peripheral blood (SPB) and in serum of the aspirated bone marrow (SABM) to concentrations of selected elements of the cytokine network (IL-2, sIL-2R, IL-6, sIL-6R, and TNF-alpha) during different phases of MM disease and to recognise whether there are some specific relations of these factor in both tissue fluids. METHODS AND RESULTS: Two groups of patients with MM were analysed: the group of 64 patients examined in different phases of MM disease and group of 39 patients examined when the disease was diagnosed (age median was 63 and 64 years, male to female relation was 1.6 and 1.3 to 1.0). CAM, cytokine and their soluble receptor levels were estimated using ELISA method. Increased levels of sVCAM-1 in APB were found in 87.5 and 87% of patients; in both groups sVCAM-1 medians almost twice exceeded the upper limits of normality (1180 and 1295 ng/ml). Levels in SABM were always higher (1347 and 1546 ng/ml) than that in SPB. Higher values of sICAM-1 in SPB had 35 and 33% of patients; sICAM-1 medians in SPB and in SABM did not exceed in either group the upper limits of normality (691 ng/ml) and they did not differ significantly (519 vs 476 and 518 vs 500 ng/ml). Statistical analysis (Pearson's correlation quotient, p < 0.05) has shown in both groups significant relation among sVCAM-1 in SPB and SABM levels (p-0.0001 and p-0.0012) and sICAM-1 level (p-0.0002 and p-0.0011) in both types of tissues fluids. In the larger group the statistically significant relation of sVCAM-1 in SPK to sIL-2R (0.0001), sIL-6R (0.0001), TNF-alpha (0.0003), and sICAM-1 (0.042) was found as well as to IL-2 (0.034, sIL-6R (0.044), and sICAM-1 (0.007) in SABM. In the group of 39 patients examined when the MM disease was diagnosed, relation of sVCAM-1 in SPB to levels of sIL-6R (0.0002) and TNF-alpha (0.0001), and in SABM only to sIL-2R (0.009). Evaluation of sICAM-1 revealed relation only to levels of sVCAM-1 both in SPK (0.042) and in SABM (0.007) in the larger group of patients. CONCLUSIONS: The described concentration changes of soluble CAM in serum of the peripheral blood and in serum of the aspirated bone marrow as well as identified relations to levels of various elements of the cytokine network indicate that CAM and especially sVCAM-1, together with elements of the cytokine network play a role in the complicated MM pathology. Particular activity of serum soluble forms sVCAM-1 and sICAM-1 in the pathogenesis of myeloma has not been clarified. It shows that analysis of soluble cytoadhesive molecules sVCAM-1 and sICAM-1 and selected elements of the cytokine network (IL-2, sIL-2R, IL-6, sIL-6R and TNF-alpha) in serum of the aspirated bone marrow has no advantage to analysis of the peripheral blood serum.

[Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma]. / Vztah hladin solubilních cytoadhezivních molekul VCAM-1 a ICAM-1 k vybraným klinickým a laboratorním ukazatelum mnohocetného myelomu.

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.