Serum levels of soluble CD23, but not soluble CD25, predict disease progression in early stage B-cell chronic lymphocytic leukemia

Serum levels of the soluble forms of CD23 (sCD23) and CD25 (sCD25) were prospectively analyzed with respect to their prognostic relevance in early stage B-cell chronic lymphocytic leukemia (B-CLL). SCD23 and sCD25 levels were determined in 105 patients with newly diagnosed B-CLL (Binet stage A). In 93 of the patients, these levels were correlated with other already established indicators for risk of disease progression, including the histologic pattern of bone marrow infiltration, lymphocyte doubling time (LDT), and the serum level of thymidine kinase (TK). High serum levels of both sCD23 and of sCD25 were associated with a diffuse bone marrow infiltration, a LDT < or = 12 months, and elevated (>5 U/L) serum TK, respectively. Moreover, examination of the clinical course of 76 untreated patients showed that high levels of sCD23, but not of sCD25, at initial diagnosis were linked with disease progression. Furthermore, in a stepwise Cox regression model, high levels of sCD23 and a short LDT were shown to be strong predictors of progressive disease within the first year of disease presentation. Therefore, it appears to be justified to incorporate sCD23 levels into the risk profile of early stage B-CLL and to take them into account for stratification in risk-adapted treatment strategies.     

Total aortic arch reconstruction for multiple great vessel occlusive disease

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), beta 2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54+ lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and beta 2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.     

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).     

Release of soluble intercellular adhesion molecule 1 into bile and serum in murine endotoxin shock

Neutrophil-induced liver injury during endotoxemia is dependent on the adhesion molecules Mac-1 (CD11b/CD18) on neutrophils and its counterreceptor on endothelial cells and hepatocytes, intercellular adhesion molecule 1 (ICAM-1). To investigate a potential release of a soluble form of ICAM-1 (sICAM-1), animals received 100 micrograms/kg Salmonella abortus equi endotoxin alone or in combination with 700 mg/kg galactosamine. In endotoxin-sensitive mice (C3Heb/FeJ), injection of endotoxin did not cause liver injury but induced a time-dependent increase of sICAM-1 in serum (300%) and in bile (615%) without affecting bile flow. In galactosamine/endotoxin-treated animals, which developed liver injury, the increase in both compartments was only 97% and 104%, respectively. In either case, the increase in sICAM-1 concentrations paralleled the enhanced ICAM-1 expression in the liver. The endotoxin-resistant strain (C3H/HeJ) did not show elevated sICAM-1 levels in serum or bile after endotoxin administration. In contrast, the intravenous injection of murine tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) or IL-1 beta (13-23 micrograms/kg) into endotoxin-resistant mice induced a 225% to 364% increase in serum sICAM-1 and a 370% elevation of the biliary efflux of sICAM-1, again independent of changes in bile flow. These data indicate that cytokines are major inducers of sICAM-1 formation during endotoxemia in vivo. The described experimental model can be used to investigate the role of sICAM-1 in the pathophysiology of inflammatory liver disease.     

Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events

We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were obtained from 119 patients with objectively-proven PAD, 39 patients with hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both p <0.01) in the patients with PAD relative to the controls, but no significant change in patients with hypercholesterolaemia. However, the effect for sVCAM-1 was lost when smoking was entered as a covariate. Only sICAM-1 was higher in patients with PAD in the femoral/iliac arteries compared to the carotid arteries (p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1 weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to end points such as myocardial infarction and arterial surgery). However, high fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05) predictor of disease progression. We suggest (i) that increased levels of sVCAM-1 in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent of this risk factor, (iii) that both these changes are independent of hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of disease progression in peripheral atherosclerosis.     

Increased serum levels of tumor necrosis factor-alpha are correlated to soluble intercellular adhesion molecule-1 concentrations in non-small cell lung cancer patients

Tumor necrosis factor (TNF)-alpha has been shown to induce shedding of ICAM-1. Experimental studies report that soluble intercellular adhesion molecule-1 (sICAM-1) may interfere with the host immunesurveillance system. Serum levels of TNF-alpha and sICAM-1 were determined by ELISA in 112 non-small cell lung cancer (NSCLC) patients. Serum concentration of TNF-alpha and sICAM-1 were related to tumor burden and progression; a significant correlation was observed between circulating levels of TNF-alpha and sICAM-1. Our study suggests that ICAM-1 could be a marker of TNF-alpha activity and that high levels of these molecules may have a prognostic value in lung cancer.     

Serum concentrations of sICAM-1, sE-, sP- and sL-selectins in patients with Schistosoma mansoni infection and association with disease severity

Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1, CD54) and of soluble E- (CD62E), but not soluble P- (CD62P) and L- (CD62 L) selectins, were detected in Malagasy patients living in an hyperendemic focus of Schistosoma mansoni. Levels of sICAM-1 remained elevated for several months after treatment with praziquantel. Serum levels of ICAM-1, but not of other markers, were significantly correlated with the disease severity, as indicated by ultrasonographical data, and with some circulating fibrosis markers (at least hyaluronic acid). sICAM-1 level may reflect endothelial inflammatory reactions, probably harmful, in the liver and may be useful for monitoring morbidity evolution in schistosomiasis mansoni.     

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.     

Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases

Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176 ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.     

Circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in head and neck cancer

The sera from patients with nasopharyngeal carcinoma (n = 30), oral carcinoma (n = 22) and laryngeal carcinoma (n = 22) was extracted before treatment. The concentration of circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) was measured by enzyme-linked immunoassay and compared with those from normal subjects (n = 20). The concentration of circulating ICAM-1, E-selectin and VCAM-1 was significantly increased in nasopharyngeal carcinoma. Correspondingly, VCAM-1 and E-selectin were significantly increased in laryngeal carcinoma, whereas only E-selectin was elevated in oral carcinoma. The concentrations of these adhesion molecules did not significantly differ with respect to the early and late stages of these carcinomas. Elevated levels of soluble adhesion molecules in the sera of cancer patients at three different head and neck regions, although appearing to be implicated in these tumour formations, may be unrelated to tumour progression.     

Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis

BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE. Pts were subdivided on the basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts with high AChRAb). Soluble adhesion molecules and cytokines were measured before the 1st and last PE, at the end of the 1st PE and in the samples of plasma filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the first PE and the course of PE led to the substantial decrease of serum levels of AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not, however, significantly influenced by both the single and the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS: Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in pts with MG indicated to the treatment by PE suggest some systemic activation of immune response which is more pronounced in pts with high circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion molecules due to their effective filtration, but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with synthetic membrane.     

Molecular comparison of soluble intercellular adhesion molecule (sICAM)-1 and sICAM-3 binding to lymphocyte function-associated antigen-1

The interactions of intercellular adhesion molecules-1 and -3 (ICAM-1 and ICAM-3) with lymphocyte function-associated antigen-1 (LFA-1) have been characterized and compared on the molecular and cellular level. Enzyme-linked immunosorbent-based molecular assays have been utilized to calculate the binding affinities of soluble ICAM-1 (sICAM-1) and soluble ICAM-3 (sICAM-3) for LFA-1. Consistent with previously published data, we found that sICAM-1 binds to LFA-1 with an affinity of approximately 60 nM. In contrast, sICAM-3 binds to LFA-1 with an affinity approximately 9 times weaker ( approximately 550 nM). Both sICAM-1 and sICAM-3 require divalent cations for binding. Specifically, both Mg2+ and Mn2+ support high affinity adhesion, although interestingly, high concentrations of Ca2+ decrease the affinity of each molecule for LFA-1 substantially. Furthermore, a panel of anti-LFA-1 monoclonal antibodies were characterized for their ability to block sICAM-1 and sICAM-3/LFA-1 interactions in molecular and cellular assays to help distinguish binding sites on LFA-1 for both molecules. Finally, molecular and cellular competition experiments demonstrate that sICAM-1 and sICAM-3 compete with each other for binding to LFA-1. The above data demonstrate that sICAM-1 and sICAM-3 share a common binding site or an overlapping binding site on LFA-1 and that the apparent differences in binding sites can be attributed to different affinities of sICAM-1 and sICAM-3 for LFA-1.     

Levels of circulating intercellular adhesion molecule 1 and E-selectin in serum and synovial fluid of juvenile chronic arthritis patients

OBJECTIVE: To measure the levels of two adhesion molecules (AM), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin), in serum and synovial fluid (SF) of patients with juvenile chronic arthritis (JCA). METHODS: Both soluble AM levels were tested, in serum and synovial fluid (SF) samples, with an enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum levels of sICAM-1 and sE-selectin in JCA patients were not significantly different from those of a control group. Synovial fluid levels of sICAM-1, but not of sE-selectin, assayed significantly higher (p < 0.05) in JCA patients than in controls. Moreover SF levels of both molecules correlated negatively with disease duration, being higher in the earliest phases. No significant correlations were found between JCA sICAM-1 and sE-selectin levels and leukocyte count or ESR. CONCLUSIONS: These observations may signify a more important role of ICAM-1 than E-selectin in the migration of inflammatory cells into JCA SF. The negative correlation of both AMSF levels in JCA patients with disease duration could reflect a higher expression of ICAM-1 and E-selectin during the earliest phases of the disease.     

The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1

The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma levels of tumour necrosis factor and its soluble receptors correlate with clinical features and outcome of Hodgkin's disease patients

A prospective study was performed to assess the use of plasma measurement of tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble receptors (p55 and p75) for prognostic risk assignment in 61 patients with Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were higher in Hodgkin's disease patients than in healthy controls. Plasma levels of TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's disease, including those related to the host (age, performance status) and to the tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and p75 were also associated with several parameters reflecting an immune activation, including the presence of B symptoms, elevated serum levels of gammaglobulins, alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia and low serum albumin levels. Finally, elevated TNF ligand receptor plasma markers were associated with a lower incidence of complete response to therapy and predicted shorter free-from-progression survival and overall survival of the patients. These results indicate that the plasma levels of TNF and its soluble receptors correlate with clinical features and outcome of patients with Hodgkin's disease.     

Elevated soluble intercellular adhesion molecule 1 in the serum of patients with polymyalgia rheumatica: influence of steroid treatment

OBJECTIVE: To determine the levels of serum soluble intercellular adhesion molecule 1 (sICAM-1) in patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) prior and during steroid therapy. METHODS: Sixteen patients with PMR and/or GCA had complete clinical and laboratory investigations at diagnosis before treatment and 9 patients were followed during 6 months of steroid therapy. Serum sICAM-1 levels were measured by ELISA: RESULTS: Serum ICAM-1 levels were higher in the patient group compared to a control population. No significant correlation was found between serum sICAM-1 levels and other indices of disease activity. After steroid administration, a dramatic fall in serum sICAM-1 levels was observed at the end of the first week and persisted until the end of the study period, paralleling clinical and laboratory disease remission. CONCLUSION: Serum sICAM-1 levels paralleled disease activity in PMR and/or GCA. Steroid treatment induced a rapid normalization of the serum sICAM-1 levels.     

Vascular endothelial cell expression of ICAM-1 and VCAM-1 at the onset of eliciting contact hypersensitivity in mice: evidence for a dominant role of TNF-alpha

We have studied vascular endothelial activation and increased expression of ICAM-1 and VCAM-1 at the onset of the elicitation phase of oxazolone contact hypersensitivity in mice. By measuring the local uptake of i.v. administered radiolabeled anti-ICAM-1 and anti-VCAM-1 mAb, we found that endothelial ICAM-1 and VCAM-1 was increased by 4 h after challenge, 2 h later than the first peak of ear swelling and 125I-labeled human serum albumen uptake. Increased expression of endothelial ICAM-1 and VCAM-1 was significantly greater in sensitized animals than in naive animals. Anti-TNF-alpha antiserum significantly inhibited both the increase in ear thickness (p < 0.01), and the up-regulation of ICAM-1 and VCAM-1 expression (p < 0.01 for both) at 4 h. In contrast, the combination of anti-IL-1alpha and IL-1beta had only a small inhibitory effect on ICAM-1 expression (p < 0.05) and no significant effect on increased ear thickness or on VCAM-1 expression. A mixture of anti-TNF-alpha, anti-IL-1alpha, and IL-1beta was no more inhibitory for endothelial ICAM-1 and VCAM-1 expression than anti-TNF-alpha alone. ICAM-1 and VCAM-1 expression at 4 h was unaffected by a combination of mAb against alpha4 and beta2 integrins, whereas expression at 24 h was significantly inhibited (p < 0.05), suggesting that the release of TNF-alpha and other cytokines involved in the initiation of the response may not require leukocyte traffic or other leukocyte functions involving these integrins. We conclude that the early up-regulation of endothelial ICAM-1 and VCAM-1 during the elicitation of contact hypersensitivity is primarily due to the immune-dependent local release of TNF-alpha.     

"Secondary" chondrosarcoma of the hand. Case report and review of the literature]

The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin is important for the regulation of the leucocyte traffic into and in inflammatory dermatoses. ICAM-1, VCAM-1 and E-selectin were initially identified as cell-surface proteins, but recent evidence suggests that they also exist in a soluble form. The collection of human afferent lymph exclusively deriving from a selected skin area allows insight into local pathomechanisms as well as signal transmission in skin disorders. In the present study we measured the concentrations of the soluble adhesion molecules (sAM) sICAM-1, sVCAM-1 and sE-selectin in human skin lymph derived from normal untreated skin, irritant contact dermatitis (CD) and the induction and elicitation phases of allergic CD. The strong elicitation reactions of allergic CD produced an increase in sAM output to about three times the baseline values but in the weaker irritant CD we observed no increase at all. In the induction phase of allergic CD the concentrations during the first 9 days of the experiment remained unchanged, as in the lymph derived from normal untreated skin, but were slightly increased thereafter. To our knowledge, no in vivo data exist on the local involvement of sAM in irritant and allergic CD in humans. Our results provide evidence of increased concentrations of sAM mainly in strong allergic CD.     

Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia

The CD44 cell surface proteoglycan participates in a variety of functions including lymphohematopoiesis, lymphocyte homing and tumor metastasis. In addition to the standard form (CD44st), a large family of variant isoforms (CD44v) is generated by alternative splicing of a single gene. Certain CD44v (v5 and V6) are upregulated in the course of neoplastic progression and reflect the metastatic potential of tumor cells. CD44 v6 is expressed in high-grade non-Hodgkin's lymphoma cells and is released in the serum, thus providing a soluble marker that reflects tumor burden, disease progression and treatment response. Here we show that serum CD44st is elevated in approximately half of B-CLL patients. In contrast, CD44v5 and v6 are detected at normal levels in the large majority of the cases. CD44st serum levels correlate significantly with the number of circulating leukemic B cells and with the levels of another soluble B-CLL marker, beta2-microglobulin. Immunoprecipitation analyses of B-CLL sera allow detection of several high molecular weight bands and of a 78 kDa band that represents a soluble form of CD44st and is 4 kDa lower than a similar band (82 kDa) detected in B-CLL cell lysates. Elevated serum CD44st associates with a number of unfavorable prognostic factors such as high peripheral blood lymphocytosis, splenomegaly, advanced disease stage and therapy requirement. A follow-up study indicates that serum levels of CD44st are related to disease status, thus reinforcing our veiw that this molecule may represent a reliable tumor marker in B-CLL.