Immune dyscrasia in adult growth hormone deficiency: Evaluation of hemolytic complement activity (CH50) and IgG subclasses.

CH50 is a screening assay for the activation of the classical complement pathway, the immunoglobulins-mediated one, activated in several inflammatory diseases. Adult growth hormone deficiency (aGHD) is recognized as a chronic inflammatory condition, although poorly evaluated under the profile of inflammatory biomarkers. The aim of this case-control observational study is to analyze CH50 and immunoglobulins G (IgG) subclasses production in aGHD, comparing this condition to healthy controls.38 subjects were included and divided as follows: aGHD (n = 18, 6 females and 12 males); healthy controls (n = 20, 10 females and 10 males). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response 30 kg/m2. The two groups were evaluated for hormonal and metabolic parameters, CH50 and IgG subtypes.IgG1 and IgG2 were significantly higher in controls than in aGHD, while IgG3 and IgG4 showed a trend to higher levels in controls, although not significant. Furthermore, CH50 levels were significantly higher in aGHD.These data substantiate the hypothesis of a dyscrasia in IgG subclasses production in aGHD. As IgG levels decrease, CH50 levels do not

Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma

Background: Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma. We sought to investigate if serum Ig FLC concentrations are affected by asthma severity and their relationships with inflammatory outcomes.Methods: By using immunoassays, we measured serum κ and λ Ig FLCs in 24 severe persistent asthma patients, 15 patients with moderate persistent asthma, 15 steroid-naïve mild persistent asthma patients and 20 healthy control subjects in a cross-sectional observational study. Total and specific serum IgE concentrations, fractional exhaled nitric oxide (FENO), lung function, peripheral blood eosinophils and neutrophils, and C reactive protein (CRP) were also measured.Results: Serum κ FLC concentrations were elevated in severe asthma patients compared mild asthma patients (p < 0.05) and healthy subjects (p < 0.05). Serum λ FLCs were higher in severe asthma patients than in healthy subjects (p < 0.05) and correlated with blood eosinophil counts (percentage, κ: r = 0.51, p = 2.9678−6; λ: r = 0.42, p = 1.7377−4; absolute values, κ: r = 0.45, p = 6.1284−5; λ: r = 0.38, p = 7.8261−4), but not with total or specific serum IgE. In severe asthma patients, serum Ig FLC correlated with serum CRP (κ: r = 0.33; p = 0.003; λ: r = 0.38, p = 8.8305−4) and blood neutrophil cell counts (percentage, κ: r = 0.31; p = 0.008; λ: r = 0.29, p = 0.01; absolute values, κ: r = 0.40; p = 3.9176−4; λ: r = 0.40, p = 4.5479−4), were elevated in subjects with blood eosinophilia (≥300 cells/µL) (n = 13) compared with non-eosinophilic subjects (n = 10) (κ: 19.2 ± 1.2 mg/L versus 12.1 ± 1.3 mg/L, p < 0.001; λ: 27.2 ± 2.6 mg/L versus 16.8 ± 2.5 mg/L, p < 0.01), but were similar in atopic (n = 15) versus nonatopic subjects (n = 9) (κ: p = 0.20; λ: p = 0.80). Serum FLC were negatively correlated with lung function tests, including forced expiratory volume in one second (FEV1) (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0035), and FEV1/forced vital capacity ratio (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0036).Conclusion: Serum Ig FLCs are elevated in severe asthma adults and might represent new surrogate markers of inflammation. The pathophysiological implications of these findings require further research. This study was approved by the ethics committee of the University Hospital Agostino Gemelli Foundation and Catholic University of the Sacred Heart (approval number P/1034/CE2012)

Ornamenti e forme architettoniche nella miniatura islamica del XIII secolo

In this analysis of the architectural elements present in Islamic miniature painting two main aspects have been considered: their role in the iconographic composition, and the parallel between painted and actual architecture. The chronological analysis showed that, while in the early years of thirteenth century such representations, often reduced to their essential architectural forms, were used as frames for the image, from the third decade of the thirteenth century such features became autonomous parts of the image. The actual architecture and the painted architecture have been analyzed by comparing both building typologies and ornamental motifs: many images of mosques, mausoleums, and tombstones present in the manuscripts of Ḥarīrī’s Maqāmāt have been compared with the contemporary architectural structures, while architectural elements and ornaments in miniatures from other two manuscripts (and Arabic Kalīla wa Dimna and the Seljukid Warqua wa Gulšāh) have been analyzed according to their chronology and typology

Design of Flat Vaults with Topological Interlocking Solids

This paper investigates the principles that regulate complex stereotomic constructions as a starting point for the design of a new two-dimensional floor structure based on the principles of TIM (Topological Interlocking Materials). These interlocking systems use an assembly of identical Platonic solids which, due to the mutual bearing between adjacent units and the presence of a global peripheral constraint, lock together to form pure geometric shapes. This type of structure offers several advantages such as a high energy dissipation capacity and tolerance towards localised failure, which has made it a popular research topic over the last thirty years. The current research project includes a case study of an assembly of interlocking cubes to create a \u201cflat vault\u201d. The resulting vault design features a striking appearance and its geometry may be manipulated to achieve different two-dimensional solutions, provided certain geometric conditions necessary for the stability of the system are followed

Cerebral Microbleeds in a Small Cohort of Patients with First Ever Lacunar Stroke. A 3Tesla MRI Longitudinal Case Series

Background: High resolution imaging may help detect early development of cerebral microbleeds (CMB) and clarify mechanisms of small vessel disease (SVD).Methods: 19 patients with lacunar stroke were recruited and 3T MRI scan was performed after the acute event and at four months. All patients were started on anti-platelet treatment after the first event. SVD severity was assessed by the age-related white matter changes (ARWMC) scale.Results: First MRI - 13 patients had No or Mild SVD (ARWMC 1-2), 6 patients had Moderate to Severe SVD (ARWMC 3-6). 3/13 of NO-MILD patients and 5/6 of MOD-SEV patients have at least 1 CMB in the first scan. Only 2 patients in the MOD-SEV group showed either enlarged or additional CMB at follow up. 3 patients in the MOD-SEV group and no patients in the NO-MILD group had at least one new asymptomatic subcortical ischemic lesion in the follow-up scan.Conclusions: Rapid development of new CMB after starting antiplatelet therapy seems to be confined in patients with severe SVD only. Subclinical vascular events in patients with moderate to severe SVD occur even when antiplatelet treatment is started. Long term effects of antiplatelet treatment in MOD-SEV patients with GRE lesions must be tested.</p

Serum and urine free light chains measurements in patients with systemic sclerosis: novel biomarkers for disease activity

Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in affected individuals as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of kappa and lambda FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free kappa/lambda ratio and kappa + lambda sum (p = 0.0001). SSc patients showed increased free kappa in urine with a kappa/lambda higher than HC (p = 0.0001). SSc patients with increased kappa + lambda in serum showed that erythro-sedimentation rate (p = 0.034), C-reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free kappa and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free kappa in urine had higher DAI (p = 0.048) than SSc patients with normal kappa levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients

Overview of immune abnormalities in lysosomal storage disorders

The critical relevance of the lysosomal compartment for normal cellular function can be proved by numbering the clinical phenotypes that arise in lysosomal storage disorders (LSDs), a group of around 70 different monogenic autosomal or X-linked syndromes, caused by specific lysosomal enzyme deficiencies: all LSDs are characterized by progressive accumulation of heterogeneous biologic materials in the lysosomes of various parts of the body such as viscera, skeleton, skin, heart, and central nervous system. At least a fraction of LSDs has been associated with mixed abnormalities involving the immune system, while some patients with LSDs may result more prone to autoimmune phenomena. A large production of proinflammatory cytokines has been observed in Gaucher and Fabry diseases, and wide different autoantibody production has been also reported in both. Many immune-mediated reactions are crucial to the pathogenesis of different inflammatory signs in mucopolysaccharidoses, and subverted heparan sulphate catabolism might dysregulate cellular homeostasis in the brain of these patients. Furthermore, an inappropriate activation of microglia is implicated in the neurodegenerative foci of Niemann-Pick disease, in which abnormal signalling pathways are activated by impaired sphingolipid metabolism. In addition, not the simple impaired catabolism of gangliosides per se, but also the production of anti-ganglioside autoantibodies contributes to the neurological disease of gangliosidoses. Even if the exact relationship between the modification of lysosomal activities and modulation of the immune system remains obscure, there is emerging evidence of different impaired immunity responses in a variety of LSDs: in this review we investigate and summarize the immune abnormalities and/or clinical data about immune system irregularities which have been described in a subset of LSDs

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis

Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG