Correlation of IgG autoantibodies against acetylcholine receptors and desmogleins in patients with pemphigus treated with steroid sparing agents or rituximab.

INTRODUCTION: Autoantibodies (autoAbs) against desmoglein-1 (DSG1) and desmoglein-3 (DSG3) have conventionally been studied and well accepted in the pathogenesis of pemphigus vulgaris (PV) and foliaceus (PF). Recent studies have suggested that non-DSG autoAbs may contribute to the pathogenesis of pemphigus, including autoAbs directed at acetylcholine receptors (AChR) and thyroid peroxidase (TPO). The purpose of this study is to retrospectively analyze PV and PF patient sera to better understand the relationship between anti-AChR and -TPO Abs to disease activity and DSG reactivity between patients treated with prednisone and steroid sparing agents (SSA; n = 22) or prednisone and rituximab (n = 21). METHODS: Patients were evaluated at 2 time points, T1 and T2, for disease activity using the Pemphigus Disease Area Index (PDAI), and sera were tested for the presence of TPO, DSG1, DSG3, muscarinic (M3) and nicotinic (n) AChR IgG autoAbs, as well as antibodies against Varicella Zoster Virus (VZV) by ELISA. RESULTS: Disease activity significantly decreased in patients from T1 to T2 (p < .0001). A significant difference was seen in IgG anti-DSG1 (p < .0001) and anti-DSG3 (p = .0049) levels when T1 was compared to T2 in both treatment groups. A significant increase was found between pemphigus patients and normal subjects with nAChR (p < .0001) at T1 but not with m3AChR, TPO or VZV Abs. No significant difference was seen between T1 and T2 values in patients with pemphigus for the non-desmoglein Abs TPO (p = .7559), M3AChR (p = .9003), nAChR (p = .5143) or VZV (p = .2454). These findings demonstrate that although an increase in IgG anti-nAChR autoAbs was found in PV and PF subjects, these Abs did not decrease with treatment. No other non-DSG Abs were increased or significantly changed over time in patients with pemphigus. This suggests that anti -AChR and -TPO Abs may not play a direct role in the pathogenesis of most patients with pemphigus, but does not rule out a role for non-DSG auto antibodies in distinct subsets of pemphigus patient.

Non-ST-Segment-Elevation Myocardial Infarction Among Patients With Chronic Kidney Disease: A Propensity Score-Matched Comparison of Percutaneous Coronary Intervention Versus Conservative Management.

BACKGROUND: Chronic kidney disease (CKD) remains an independent predictor of cardiovascular morbidity and mortality. CKD complicates referral for percutaneous coronary intervention (PCI) in non-ST-segment-elevation myocardial infarction (NSTEMI) patients because of the risk for acute kidney injury and the need for dialysis, with American College of Cardiology/American Heart Association guidelines underscoring the limited data on these patients. METHODS AND RESULTS: Using the National Inpatient Sample to analyze hospitalizations in the United States from 2004 to 2014, we sought to assess PCI utilization and in-hospital outcomes in NSTEMI admissions with CKD. NSTEMI admissions were identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code 410.7. CKD admissions were identified by ICD-9-CM code 585. Propensity score-matched cohorts of patients with NSTEMI were matched for age, sex, comorbidities, race, median household income, primary payer status, and hospital characteristics. Of 4 488 795 hospitalizations for NSTEMI, 31% underwent PCI. Overall, 89% of admissions had no CKD. In addition, 32% of NSTEMI admissions with no CKD and 23%, 14%, and 22% with CKD stages 3, 4, and 5 underwent PCI, respectively. Hospitalized NSTEMI patients with CKD stages 4 and 5 had 41% and 20% less likelihood, respectively, of undergoing PCI compared with those with no CKD. Among hospitalized NSTEMI patients with no CKD or CKD stage 3, 4, or 5, PCI-treated groups had 63%, 57%, 39%, and 59% lower likelihood, respectively, of all-cause, in-hospital mortality compared with propensity score-matched medically managed groups. CONCLUSIONS: PCI use decreased among hospitalized NSTEMI patients as CKD severity increased, and all-cause, in-hospital mortality was greater for NSTEMI patients admitted with more severe CKD regardless of treatment strategy.