Enrichment of total serum IgG4 in patients with pemphigus.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in patients with pemphigus. OBJECTIVES: The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus. METHODS: IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay. RESULTS: Dsg-specific antibodies comprised a median of 7·1% and 4·2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with age-matched controls (P = 0·004 and P = 0·005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions. CONCLUSIONS: Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.

Investigations into the sterility of manually assembled extracorporeal circuits with vented reservoirs.

This study was designed to investigate the ability of an extracorporeal circuit (ECC) with a vented hard shell reservoir to remain sterile for a period of 72 h under dry conditions. The study was conducted in three phases. In Phase One: Two previously published methods for detecting contamination of the ECC were compared. A group of positive controls was collected by contaminating identical circuits with a known level of Enterobacter cloacae (ATTC: 13047) before initiating a regimen of "sample-dilute-sample" culturing. Negative controls for this phase were conducted by randomly sampling 1 L per manufacturer's lot of lactated ringers with each detection method. Culture results suggest that large volume filtration, but not small aliquot sampling, is sensitive to extremely low levels of contamination. No growth was detected in any negative control samples. In Phase Two: 19 ECC consisting of a membrane oxygenator, vented hardshell reservoir, arterial filter, and PVC tubing were removed from their sterile packages, assembled, and left unprotected in the moderate traffic environment of a research laboratory. The circuits were then primed with Lactated Ringer's solution. The prime solution was sampled for aerobic contamination by large volume filtration. None of the 19 samples detected contamination. In Phase Three: 43 ECC identical to the Phase Two circuits were assembled and left unprotected in the substerile pump room. The circuits were then primed, circulated, and cultured as in Phase Two. One of the 43 samples was discarded because of a recognized break in aseptic technique during sample collection. None of the remaining samples detected contamination. Mathematical calculations of binomial probabilities suggest that the chance of an open ECC developing a detectable level of contamination within 72 h of its dry assembly is insignificant.

Perioperative distribution of pulmonary vascular resistance in patients undergoing coronary artery surgery.

This study was undertaken to measure distribution of pulmonary vascular resistance (PVR) perioperatively in patients undergoing coronary artery bypass grafting (CABG) and to examine the effects of cardiopulmonary bypass (CPB) on pulmonary capillary pressure (Pc) relative to wedge pressure (Pw). Pulmonary artery catheters were placed before anesthetic induction in 18 patients scheduled for elective CABG and systemic hemodynamic variables were measured. Pulmonary artery pressure was recorded during balloon inflation and stored for off-line determination of Pc. Data were collected prior to induction (baseline), as well as after induction and intubation, skin incision, sternotomy, protamine administration, and chest closure. At each data point, downstream (capillary plus venous segments) resistance (Rds) contributed approximately 60% of total PVR and did not change significantly during the operation. PVR decreased (P < 0.05) after CPB and protamine administration, primarily due to a decrease in the absolute magnitude of the upstream (arterial) resistance. Administration of large-dose opioid anesthesia had no significant effect (P > 0.05) on total PVR or on segmental distribution of vascular resistance. At all data points, Pc was significantly larger than Pw (P < 0.05). This study demonstrates that perioperative measurement of Pc is feasible, that during CABG under these conditions, relative contribution of arterial and venous resistances remain relatively unchanged, that Pc is always larger than Pw, and that the administration of large-dose opioid anesthesia has a minimal effect on pulmonary vascular hemodynamics.