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Immunoglobulin G (IgG) antibodies in the form of high-dose intravenous immunoglobulin (IVIG) exert immunomodulatory activity and are used in this capacity to treat inflammatory and autoimmune diseases. Reductionist approaches have revealed that terminal sialylation of the single asparagine-linked (N-linked) glycan at position 297 of the IgG1 Fc bestows antiinflammatory activity, which can be recapitulated by introduction of an F241A point mutation in the IgG1 Fc (FcF241A). Here, we examined the antiinflammatory activity of CHO-K1 cell-produced FcF241A in vivo in models of autoimmune inflammation and found it to be independent of sialylation. Intriguingly, sialylation markedly improved the half-life and bioavailability of FcF241A via impaired interaction with the asialoglycoprotein receptor ASGPR. Further, FcF241A suppressed inflammation through the same molecular pathways as IVIG and sialylated IgG1 Fc and required the C-type lectin SIGN-R1 in vivo. This contrasted with FcAbdeg (efgartigimod), an engineered IgG1 Fc with enhanced neonatal Fc receptor (FcRn) binding, which reduced total serum IgG concentrations, independent of SIGN-R1. When coadministered, FcF241A and FcAbdeg exhibited combinatorial antiinflammatory activity. Together, these results demonstrated that the antiinflammatory activity of FcF241A requires SIGN-R1, similarly to that of high-dose IVIG and sialylated IgG1, and can be used in combination with other antiinflammatory therapeutics that rely on divergent pathways, including FcAbdeg.

We evaluated the usefulness of roentgenographic tracheal tube cuff shadow to tracheal wall diameter ratio (CTW ratio) and cuff minus tracheal diameter difference (C-T diameter) in estimating intracuff pressure (ICP) in intubated and mechanically ventilated patients. Seventy-one measurements of ICP, CTW ratio and C-T diameter were obtained from 20 mechanically ventilated male patients intubated with high volume low pressure cuffs in the surgical and medical intensive care units. The mean age was 61 years (range 30 to 83 years). ICP was measured by one observer, while CTW ratio and C-T diameter was measured by another observer. No significant relationship was seen between ICP and CTW ration (r = 0.092, p = 0.873), or between ICP and C-T diameter (r = 0.093, p = 0.42) by linear regression analysis. In conclusion, roentgenographic estimation of ICP by portable plain chest films in intensive care units was not found useful in this study.

Bronchial asthma is a common disease that is not yet completely understood. We specify the basic evaluation that asthmatic patients should undergo and discuss some aspects of pathophysiology. Guidelines to select patients for further evaluation are suggested.