Upregulation of Soluble HLA‐G5 and HLA‐G6 Isoforms in the Milder Histopathological Stages of Helicobacter pylori Infection: A Role for Subverting Immune Responses?

The subversion mechanisms employed by Helicobacter pylori (H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA‐G, a non‐classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA‐G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty‐four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti‐HLA‐G monoclonal antibody. As a result, HLA‐G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA‐G was significantly associated with milder colonization by H. pylori (P < 0.02), milder inflammatory activity (P < 0.02) and bacterium histological location in the gastric antrum. This study is the first to explore HLA‐G expression in the context of bacterial infection. Whether the biological role of HLA‐G during H. pylori infection is beneficial or hazardous for patients remains to be defined.     

HLA‐G and its KIR ligands in cancer – another enigma yet to be solved?

Alterations of antigen-presenting human leukocyte antigen (HLA) molecules often occur in cancer and represent one of the mechanisms by which tumours evade host immunosurveillance. One such molecule, HLA-G, was recently implicated in the same context. HLA-G is thought to mediate the tolerance of the semi-allogeneic fetus during pregnancy, by inhibiting maternal immune response through interaction with different HLA-G-recognizing killer-cell inhibitory receptors (KIRs). A report in this issue of the journal demonstrates for the first time the expression of HLA-G and its KIR ligand, ILT-2 in human breast cancer. Apart from the up-regulation on tumour cells, the authors describe HLA-G induction on the macrophages and T cells infiltrating the breast cancer lesions. Moreover, a subset of infiltrating cells also expressed HLA-G-recognizing KIR, ILT-2. This editorial discusses the induction of HLA-G and related KIR molecules as another mechanism for tumours to escape immune recognition.     

Poly[3,4‐dihydroxybenzhydrazide]: A Polydopamine Analogue?

3,4‐Dihydroxybenzhydrazide (DHBH) could be considered a structural analogue of dopamine, forming polymers under oxidative conditions in a polydopamine (PDA) fashion. However, the former turns out to be more reluctant to oxidize and thus, more drastic conditions must be applied to achieve polymerization. Heating of DHBH in the presence of ammonium peroxydisulfate in Tris buffer yields a mixture of oligomers (average 9–10 monomer units). Although it looks black like PDA, its structure is very different. The polymer is not built up by C? C bond formation but by replacement of hydroxyl groups resulting in acylhydrazine, acylhydrazone, and 1,3,4‐oxadiazoline bridging. Since the catechol moiety of the starting material is destroyed, the polymer lacks the mussel‐like anchoring property found in PDA.     

Feeling “Pooped” and “Run Down?”: Fatigue Experiences in Latino Cancer Patients

The purpose of this study was to describe fatigue and the utility of the Multidimensional Fatigue Symptom Inventory‐Short Form (MFSI‐SF) to assess fatigue among Latino cancer patients. Twenty‐two female and thirteen male Latino cancer patients participated in one of seven focus groups that took place in the southern California USA‐Mexico border region. Participants were asked to describe their fatigue experiences; participants also completed the MFSI‐SF and provided feedback about the items. Content analyses indicate that there are gender differences in the salience of the challenges that fatigue poses. Men tended to focus on physical symptoms, whereas women tended to focus on the impairment in role fulfillment. Findings have implications for intervention and health education efforts in Latino cancer patients.     

Astrocytes and NG2‐glia: what's in a name?

Classic studies recognize two functionally segregated macroglial cell types in the central nervous system (CNS), namely astrocytes and oligodendrocytes. A third macroglial cell type has now been identified by its specific expression of the NG2 chondroitin sulphate proteoglycan (NG2-glia). These NG2-glia exist abundantly in both grey and white matter of the mature CNS and are almost as numerous as astrocytes. It is well established that NG2-glia give rise to oligodendrocytes. However, the majority of NG2-glia in the adult CNS proliferate very slowly and are non-motile. Both astrocytes and NG2-glia display a stellate morphology and express ion channels and receptors to neurotransmitters used by neurons. Both types of glia make intimate contacts with neurons in grey and white matter, and their functional differences and similarities are only beginning to be unravelled. Recent observations emphasize the need to examine the relationship between astrocytes and NG2-glia, and address the question of whether they represent overlapping or two distinct glial cell populations. To be of any relevance, this classification must relate to specific functions in the neural network. At present, the balance of evidence is that NG2-glia and astrocytes are functionally segregated populations.     

Choroidal abnormalities in café‐au‐lait syndromes: a new differential diagnostic tool?

The best known café‐au‐lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café‐au‐lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty‐four patients with NF1 (14 with a truncating mutation, 14 with a non‐truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non‐truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow‐up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.     

Fibroblast Growth Factor 23, Hepatocyte Growth Factor,Interleukin‐6, High‐Sensitivity C‐Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?

Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF‐23), hepatocyte growth factor (HGF), interleukin‐6 (Il‐6), high‐sensitivity C‐reactive protein (hs‐CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF‐23 and HGF with the earlier recognized inflammatory markers Il‐6 and hs‐CRP or suPAR. All patients studied had significantly elevated levels of FGF‐23, HGF, hs‐CRP and suPAR as compared to the controls. Il‐6 and hs‐CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il‐6 and Ln CRP (R 0.28–0.37). Ln FGF‐23 correlated only with Ln HGF (r = ?0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF‐23 with the recognized inflammatory markers Il‐6, hs‐CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il‐6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF‐23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.     

A 7‐year follow‐up study of the Mindfulness‐Based Program for Infertility: Are there long‐term effects?

The Mindfulness‐Based Program for Infertility (MBPI) was developed for people facing infertility and proved effective in cultivating mindfulness skills, improving infertility self‐efficacy, and decreasing depression, shame, entrapment, and defeat feelings. Fifty‐five women attended the MBPI sessions and completed self‐report measures of depression, anxiety, mindfulness, and experiential avoidance at post‐MBPI (T1), 6‐month follow‐up (T2), and 7‐year follow‐up (T3). There were significant direct time effects regarding experiential avoidance (F = 3.81; p < 0.033; η_p² = 0.08), the mindfulness facets describing (F = 3.54; p = 0.037; η_p² = 0.13), acting with awareness (F = 6.87; p = 0.002; η_p² = 0.22), nonjudging of inner experience (F = 10.66; p < 0.001; η_p² = 0.31), and depressive symptoms (F = 4.85; p = 0.020; η_p² = 0.10). There was an increase in the describing facet from T1 to T3 (p = 0.036). The act with awareness facet increased from T1 to T2 (p = 0.010) and from T1 to T3 (p = 0.007), as well as the nonjudging of inner experience facet (T1 to T2 [p = 0.030] and T1 to T3 [p = 0.002]). Experiential avoidance decreased from T1 to T3 (p = 0.022) and depressive symptoms from T1 to T2 (p = 0.019). Post‐MBPI scores were maintained at T2 and T3 concerning anxiety symptoms and the observing and no‐reactivity mindfulness facets. There were long‐term effects of MBPI on mindfulness and experiential avoidance. Moreover, therapeutic gains were maintained regarding depression and anxiety symptoms, independently of the reproductive outcome.     

IL‐17/Th17 in anti‐fungal immunity: What's new?

How the immune system tailors protective responses to suit the infectious challenge while limiting damage to the host is an emerging theme in T‐cell biology. Although many studies have focused on the pathological aspects of IL‐17‐producing T cells in many autoimmune diseases, their role in protective anti‐microbial immunity has also been increasingly recognized. This increased recognition also applies to their role in anti‐fungal immunity; however, the role of IL‐17‐producing T cells in protection versus pathology in fungal infections is still controversial. Although both positive and negative effects on immune resistance have been attributed to the IL‐23/Th17 axis in experimental models of fungal infections, defective Th17 cell differentiation has been linked to recurrent pneumonia by filamentous fungi and the occurrence of mucocutaneous candidiasis in patients with primary immunodeficiencies. Here we discuss how recent findings in experimental candidiasis and aspergillosis shed new lights on the contribution of Th17 cells to resistance and pathology to fungi.