The unique properties of IgG4 and its roles in health and disease

IgG4 has unique functional characteristics that are increasingly recognized to have a pathogenic role in autoimmunity, tumour immunology, IgG4-related diseases and anti-biologic responses, as well as a beneficial role in allergy and parasitic infections.IgG4 is the least abundant subclass of IgG in human serum and has unique functional features. IgG4 is largely unable to activate antibody-dependent immune effector responses and, furthermore, undergoes Fab (fragment antigen binding)-arm exchange, rendering it bispecific for antigen binding and functionally monovalent. These properties of IgG4 have a blocking effect, either on the immune response or on the target protein of IgG4. In this Review, we discuss the unique structural characteristics of IgG4 and how these contribute to its roles in health and disease. We highlight how, depending on the setting, IgG4 responses can be beneficial (for example, in responses to allergens or parasites) or detrimental (for example, in autoimmune diseases, in antitumour responses and in anti-biologic responses). The development of novel models for studying IgG4 (patho)physiology and understanding how IgG4 responses are regulated could offer insights into novel treatment strategies for these IgG4-associated disease settings.Functional Genomics of Muscle, Nerve and Brain Disorder

An adaptive, real-time cadence algorithm for unconstrained sensor placement

This paper evaluates a new and adaptive real-time cadence detection algorithm (CDA) for unconstrained sensor placement during walking and running. Conventional correlation procedures, dependent on sensor position and orientation, may alternately detect either steps or strides and consequently suffer from false negatives or positives. To overcome this limitation, the CDA validates correlation peaks as strides using the Sylvester's criterion (SC). This paper compares the CDA with conventional correlation methods.22 volunteers completed 7 different circuits (approx. 140 m) at three gaits-speeds: walking (1.5 m s- 1), running (3.4 m s- 1), and sprinting (5.2 and 5.7 m s- 1), disturbed by various gait-related activities. The algorithm was simultaneously evaluated for 10 different sensor positions. Reference strides were obtained from a foot sensor using a dedicated offline algorithm.The described algorithm resulted in consistent numbers of true positives (85.6-100.0%) and false positives (0.0-2.9%) and showed to be consistently accurate for cadence feedback across all circuits, subjects and sensors (mean ± SD: 98.9 ± 0.2%), compared to conventional cross-correlation (87.3 ± 13.5%), biased (73.0 ± 16.2) and unbiased (82.2 ± 20.6) autocorrelation procedures.This study shows that the SC significantly improves cadence detection, resulting in robust results for various gaits, subjects and sensor positions

Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial

Background: Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Methods/design: Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. Discussion: We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. Trial registration: This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013on August 25th 2016. © 2017 The Author(s)

Impact of structural modifications of IgG antibodies on effector functions

Immunoglobulin G (IgG) antibodies are a critical component of the adaptive immune system, binding to and neutralizing pathogens and other foreign substances. Recent advances in molecular antibody biology and structural protein engineering enabled the modification of IgG antibodies to enhance their therapeutic potential. This review summarizes recent progress in both natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor binding optimization. We discuss the functional consequences of these modifications to highlight their potential for therapeutical applications