Specificity and affinity of human Fc{gamma} receptors and their polymorphic variants for human IgG subclasses.

International audienceDistinct genes encode six human receptors for IgG (hFcgammaRs), three of which have two or three polymorphic variants. The specificity and affinity of individual hFcgammaRs for the four human IgG subclasses is unknown. This information is critical for antibody-based immunotherapy which has been increasingly used in the clinics. We investigated the binding of polyclonal and monoclonal IgG1, IgG2, IgG3 and IgG4 to FcgammaRI, FcgammaRIIA, IIB and IIC, FcgammaRIIIA and IIIB and all known polymorphic variants. Wt and low-fucosylated IgG1 anti-CD20 and anti-RhD mAbs were also examined. We found: 1) that IgG1 and IgG3 bind to all hFcgammaRs; 2) that IgG2 bind not only to FcgammaRIIAH131, but also, with a lower affinity, to FcgammaRIIAR131 and FcgammaRIIIAV158; 3) that IgG4 bind to FcgammaRI, FcgammaRIIA, IIB and IIC and FcgammaRIIIAV158; 4) that the inhibitory receptor FcgammaRIIB has a lower affinity for IgG1, IgG2 and IgG3 than all other hFcgammaRs. We also identified parameters which determine the specificity and affinity of hFcgammaRs for IgG subclasses. These results document how hFcgammaR specificity and affinity may account for the biological activities of antibodies. They therefore highlight the role of specific hFcgammaRs in the therapeutic and pathogenic effects of antibodies in disease

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke

Background\ud There are a number of different approaches to physiotherapy treatment following stroke that, broadly speaking, are based on neurophysiological,\ud motor learning and orthopaedic principles. Some physiotherapists base their treatment on a single approach, while others\ud use a mixture of components from a number of different approaches.\ud Objectives\ud To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy\ud treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles.\ud Search strategy\ud We searched the Cochrane Stroke Group Trials Register (last searchedMay 2005), the Cochrane Central Register of Controlled Trials\ud (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL\ud (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation.\ud Selection criteria\ud Randomised or quasi-randomised controlled trials of physiotherapy treatment approaches aimed at promoting the recovery of postural\ud control and lower limb function in adult participants with a clinical diagnosis of stroke. Outcomes included measures of disability,\ud motor impairment or participation.\ud Data collection and analysis\ud Two review authors independently categorised the identified trials according to the inclusion and exclusion criteria, documented their\ud methodological quality, and extracted the data.\ud Main results\ud Twenty-one trialswere included in the review, five ofwhichwere included in two comparisons. Eight trials compared a neurophysiological\ud approach with another approach; eight compared a motor learning approach with another approach; and eight compared a mixed approach with another approach. Amixed approach was significantly more effective than no treatment or placebo control for improving\ud functional independence (standardised mean difference (SMD) 0.94, 95% confidence intervals (CI) 0.08 to 1.80). There was no\ud significant evidence that any single approach had a better outcome than any other single approach or no treatment control.\ud Authors' conclusions\ud There is evidence that physiotherapy intervention, using a mix of components from different approaches, is significantly more effective than no treatment or placebo control in the recovery of functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy approach is more effective in promoting recovery of lower limb function or postural control following stroke than any other approach. We recommend that future research should concentrate on investigating the effectiveness of clearly described individual techniques and task-specific treatments, regardless of their historical or philosophical origin.\ud \ud Plain language summary\ud \ud Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke\ud Physiotherapy, using a mix of components from different treatment approaches, appears best for promoting functional independence following stroke; no single physiotherapy approach is clearly best for promoting recovery after stroke. A stroke interrupts the blood flow to the brain, often leading to damage to some brain functions. This can cause paralysis of some parts of the body or other difficulties with various physical functions. Physiotherapy is an important part of rehabilitation for people who have had a stroke. A number of physiotherapy approaches have been developed based on different ideas about how people recover after a stroke. This review of 21 trials found there is no evidence that any one approach was clearly better than another for improving leg strength, balance, walking speed or the ability to perform everyday tasks. However, physiotherapy using a mixture of components from the different approaches was better than no treatment or placebo treatment for improving aspects of function following a stroke