Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions.

BACKGROUND: Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)-activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown. OBJECTIVES: To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches. METHODS: We determined the rates of ASST+/BT- and ASST-/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD). RESULTS: The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT-: 22%, ASST-/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA-: 18.8% and ASST-/BHRA+: 16.7%) and 31.3% (ASST+/BAT-: 6.3% and ASST-/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA-: 18.8%, ASST-/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD-: 10.0% and ASST-/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002). CONCLUSIONS: The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum-induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.

The blockade of angiotensin AT1 and aldosterone receptors protects rats from synthetic androgen-induced cardiac autonomic dysfunction.

AIM: This study aimed to evaluate the combined effects of exercise and antagonists of the angiotensin II and aldosterone receptors on cardiac autonomic regulation and ventricular repolarization in rats chronically treated with nandrolone decanoate (ND), a synthetic androgen. METHODS: Thirty male Wistar rats were divided into six groups: sedentary, trained, ND-treated, trained and ND-treated, trained and treated with both ND and spironolactone, and trained and treated with both ND and losartan. ND (10 mg kg(-1) weekly) and the antagonists (20 mg kg(-1) daily) of the angiotensin II AT1 (losartan) and aldosterone (spironolactone) receptors were administered for 8 weeks. Exercise training was performed using a treadmill five times each week for 8 weeks. Following this 8-week training and treatment period, electrocardiogram recordings were obtained to determine the time and frequency domains of heart rate variability (HRV) and corrected QT interval (QTc). RESULTS: Nandrolone decanoate treatment increased the QTc interval and reduced the parasympathetic indexes of HRV (RMSSD, pNN5 and high-frequency power) in sedentary and trained rats. The ratio between low- and high-frequency power (LF/HF) was higher in ND-treated groups. Both losartan and spironolactone treatments prevented the effects of ND on the QTc interval and the HRV parameters (RMSSD, pNN5, high-frequency power, and the LF/HF ratio). CONCLUSION: Our results show that chronic treatment with a high dose of ND induces cardiac parasympathetic dysfunction and disturbances in ventricular repolarization in both sedentary and exercised rats. Furthermore, inhibiting the renin-angiotensin-aldosterone system using losartan, or spironolactone, prevented these deleterious effects.

Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels.

Common variable immunodeficiency disorders (CVID), the most frequent cause of symptomatic primary immunodeficiency, are defined by impaired antibody production. Notwithstanding, T cell activation and granulomatous manifestations represent the main causes of CVID morbidity even in patients receiving immunoglobulin (Ig) G replacement therapy. Additionally, gut pathology is a frequent feature of CVID. In this study, we investigated monocyte imbalances and their possible relationship with increased microbial translocation in CVID patients. Monocyte subsets were defined according to CD14 and CD16 expression levels and evaluated in terms of human leucocyte antigen D-related (HLA-DR), CD86 and programmed death-1 molecule ligand 1 (PD-L1) expression by flow cytometry, in parallel with the quantification of plasma lipopolysaccharide (LPS) and serum levels of soluble CD14 (sCD14), LPS-binding protein (LBP) and anti-LPS antibodies. CVID patients (n=31) featured significantly increased levels of serum sCD14 and an expansion of CD14(bright) CD16(+) monocytes in direct correlation with T cell and B cell activation, the latter illustrated by the frequency of the CD21(low) CD38(low) subset. Such alterations were not observed in patients lacking B cells due to congenital agammaglobulinaemia (n=4). Moreover, we found no significant increase in circulating LPS or LBP levels in CVID patients, together with a relative preservation of serum anti-LPS antibodies, in agreement with their presence in commercial IgG preparations. In conclusion, CVID was associated with monocyte imbalances that correlated directly with T cell activation markers and with B cell imbalances, without an association with plasma LPS levels. The heightened monocyte activated state observed in CVID may represent an important target for complementary therapeutic strategies.