Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation.

BACKGROUND: Activated hepatic macrophages play a key role in inflammation and fibrosis progression in chronic liver disease. AIM: To assess the prognostic value of soluble (s)CD163 and mannose receptor (sMR) in cirrhotic patients and explore associations with markers of intestinal permeability (lactulose-mannitol ratio, diamine oxidase), bacterial translocation (endotoxin, lipopolysaccharide-binding protein) and markers of systemic immune activation (interleukin-6, interleukin-8, sCD14). METHODS: We prospectively investigated 101 cirrhotic patients (Child-Pugh class A: n = 72, Child-Pugh classes B and C: n = 29) and 31 healthy controls. Patients were observed for a median follow-up of 37 months. RESULTS: Median plasma levels of sCD163 and soluble mannose receptor were significantly elevated in cirrhotic patients (P < .001) and increased with disease severity (sCD163 in healthy controls = 1.3, Child-Pugh class A = 4.2, Child-Pugh classes B and C = 8.4 mg/L; sMR in healthy controls = 15.8, Child-Pugh class A = 36.5, Child-Pugh classes B and C = 66.3 µg/dL). A total of 21 patients died during the observation period. Patients with sCD163 levels above 5.9 mg/L showed significantly reduced survival (survival rate after 36 months: 71% versus 98%, P < .001). Patients with soluble mannose receptor levels above 45.5 µg/dL developed significantly more complications of cirrhosis within 12 months (73% versus 9%, P < .001). Furthermore, both variables correlated with the lactulose-mannitol ratio, diamine oxidase, lipopolysaccharide and interleukin-8. CONCLUSION: Our data demonstrate the prognostic value of sCD163 in predicting long-term survival in patients with liver cirrhosis and identify soluble mannose receptor as a prognostic marker for occurrence of cirrhosis-associated complications. The correlation between gut barrier dysfunction and activation of macrophages points towards a link between them.

Reduced-intensity allografting in patients with therapy-related myeloid neoplasms and active primary malignancies.

Therapy-related myeloid neoplasms (t-MNs) are severe long-term consequences of cytotoxic treatments for a primary, often, malignant disorder. So far, the majority of patients eligible for transplantation have undergone myeloablative allo haematopoietic SCT (HSCT) as a potentially curative treatment, but it has been associated with high transplantation-related mortality (TRM) rates. In this retrospective study, we analysed the outcome of patients with t-MNs undergoing HSCT with reduced-intensity conditioning (RIC). Of 55 patients, seen at a single centre over a 10-year period, 17 underwent RIC HSCT with related or unrelated donors. The estimated overall survival was 53% at 1 year and 47% at 3 years, and disease-free survival was 47% at 1 year. At 1 year, the cumulative incidence of relapse and TRM were 24% and 30%, respectively. Of five patients with active primary neoplasms who underwent transplantation, two are alive beyond 1 year and show CR of both t-MNs and the primary malignancy. These data indicate that RIC HSCT is an encouraging approach for patients with t-MNs. The issue of primary malignancies not being in remission at the time of transplantation should be explored in further studies.

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs). METHODS: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro. RESULTS: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14-12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment. CONCLUSION: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs.

Function and activation state of platelets in vitro depend on apheresis modality.

BACKGROUND AND OBJECTIVES: In multicomponent collection, various blood components are prepared during one apheresis process. The aim of this prospective crossover study was to compare the function, metabolic parameters and activation state of fresh and stored platelets (PLTs) collected by two different cell separators. MATERIALS AND METHODS: Twenty-four donors underwent apheresis on each of two cell separators (Fenwal Amicus(®) and CaridianBCT Trima Accel(®)) with an interval of at least 2 months between donations. Per donation, one double dose of PLT concentrate (PC) and one unit of packed red-blood-cells were collected. In total, 48 single unit PCs were tested for pH, glucose, bicarbonate, lactate, potassium and LDH concentration during 7 days of storage. PLT function was analysed by aggregometry, rotation thrombelastometry and hypotonic shock response. The PLT surface expression of P-selectin (CD62P) and LAMP-3 (CD63) was estimated by flow cytometry. RESULTS: During storage, metabolic parameters were well maintained in both groups, but levels of glucose and pH were significantly lower, while lactate and LDH were significantly higher in Amicus(®)-PCs. Amicus(®)-derived PLTs were significantly more activated as evidenced by higher CD62P and CD63 expression. In parallel, the in vitro function of Amicus(®)-PLTs was significantly reduced compared to Trima(®)-PLTs. CONCLUSION: In multicomponent apheresis, standardized PLT collection is effective and well tolerated. The higher activation of Amicus(®)-derived PLTs may be because of the divergent centrifugation modalities during collection. Possible consequences for the clinical outcome of thrombocytopenic patients will be evaluated in further trials.

The basophil activation test in the diagnosis of allergy: technical issues and critical factors.

BACKGROUND: The basophil activation test (BAT) is a widely validated and reliable tool especially for the diagnosis of hymenoptera venom allergy. Nevertheless, several pitfalls have to be considered and outcomes may differ because of diverse in-house protocols and commercially available kits. We aimed to identify the factors that may influence results of the CD63-based BAT. METHODS: Basophil responses to monoclonal anti-IgE (clone E124.2.8) and bee and wasp venom were determined by BAT based on CD63. The effect of stimulating factors such as, IL-3, cytochalasin B and prewarming of the samples was investigated. Furthermore, we compared two different flow cytometer systems and evaluated the influence of storage time, different staining protocols and anti-allergic drugs on the test results. RESULTS: Interleukin-3 enhanced the reactivity of basophils at 300 pM, but not at 75 and 150 pM. Prewarming of samples and reagents did not affect basophil reactivity. CD63 expression assayed after storage time of up to 48 h showed that basophil reactivity already started to decline after 4 h. Basophils stained with HLA-DR-PC5 and CD123-PE antibodies gated as HLA-DR(neg)/CD123(pos) cells showed the highest reactivity. No effect on test outcomes was observed at therapeutic doses of dimetindene and desloratadine. Finally, slight differences in the percentage of activated basophils, depending on the cytometer system used, were found. CONCLUSION: Basophil activation test should be performed as early as possible after taking the blood sample, preferably within 4 h. In contrast to the skin test, BAT can be performed in patients undergoing treatment with antihistamines. For reasons of multiple influencing factors, BAT should be performed only at validated laboratories.

Influence of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy.

BACKGROUND: Detection of specific IgE for Hymenoptera venoms and skin tests are well established diagnostic tools for the diagnosis of insect venom hypersensitivity. The aim of our study was to analyze the effect of total IgE levels on the outcome of generalized anaphylactic reactions after a Hymenoptera sting. METHODS: Two hundred and twenty patients allergic to bee, wasp, or European hornet venom were included in the study. Their specific and total IgE levels, serum tryptase levels, skin tests, and sting history were analyzed. RESULTS: In patients with mild reactions (grade I, generalized skin symptoms) we observed higher total IgE levels (248.0 kU/l) compared to patients with moderate reactions (grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms; 75.2 kU/l) and severe reactions (grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness; 56.5 kU/l; P < 0.001). Accordingly, 25% of the patients with low levels of total IgE (<50 kU/l), but no individual with total IgE levels >250 kU/l, developed loss of consciousness (P = 0.001). Additionally, specific IgE levels were related to total IgE levels: Specific IgE levels increased from 1.6 to 7.1 kU/l in patients with low (<50 kU/l) and high (>250 kU/l) total IgE levels, respectively (P < 0.001). Specific IgE levels correlated inversely to the clinical reaction grades, however, this trend was not statistically significant (P = 0.083). CONCLUSION: Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.