SummaryThe complement alternative pathway is a powerful arm of the innate immune system that enhances diverse inflammatory responses in the human host. Key to the effects of the alternative pathway is properdin, a serum glycoprotein that can both initiate and positively regulate alternative pathway activity. Properdin is produced by many different leukocyte subsets and circulates as cyclic oligomers of monomeric subunits. While the formation of non‐physiological aggregates in purified properdin preparations and the presence of potential properdin inhibitors in serum have complicated studies of its function, properdin has, regardless, emerged as a key player in various inflammatory disease models. Here, we review basic properdin biology, emphasizing the major hurdles that have complicated the interpretation of results from properdin‐centered studies. In addition, we elaborate on an emerging role for properdin in thromboinflammation and discuss the potential utility of properdin inhibitors as long‐term therapeutic options to treat diseases marked by increased formation of platelet/granulocyte aggregates. Finally, we describe the interplay between properdin and the alternative pathway negative regulator, Factor H, and how aiming to understand these interactions can provide scientists with the most effective ways to manipulate alternative pathway activation in complex systems.
INTRODUCTION: Left ventricular assist devices (LVADs) are used in patients with advanced systolic heart failure as a bridge to cardiac transplant or as destination therapy. LVADs provide a survival benefit in this population but pose a significant risk of infection, typically of the driveline. Gastrointestinal-related infectious complications of LVADs, including erosion into the GI tract, or a device-related enteric fistula are less common. Here we present a case of enteric LVAD erosion discovered while investigating unusual blood culture results. CASE DESCRIPTION/METHODS: A 52 year old man with history of alcohol-related cardiomyopathy now with LVAD and chronic driveline infections with Stenotrophomonas, E. cloacae, MRSA, and MSSA on suppressive antibiotics was admitted to our hospital after outpatient blood cultures grew C. albicans. He reported fatigue and forty-pound weight loss during the previous three months. He denied fevers, abdominal pain, nausea, vomiting, change in appetite or early satiety. On admission, the patient was afebrile. On physical exam, he was in no distress, the abdomen was soft and not tender. There was purulent drainage from the driveline site, unchanged from prior admissions. Given his unusual history of bloodstream infections with Lactobacillus, Enterobacter, E. coli, and now Candida, there was concern for a bowel connection to the LVAD. Cross-sectional imaging with PO contrast revealed expected positioning of the LVAD abutting the gastric body and significant hardware scatter artifact, limiting the examination (Figure 1). The patient therefore underwent bidirectional endoscopy and EGD revealed two areas of ulceration and exposed LVAD hardware eroding into the greater curvature of the gastric body (Figure 2). The patient underwent subsequent explant and replacement of the LVAD. Two defects in the gastric body, one near the cardia and the other near the antrum were repaired by omental flap placement and gastrorrhaphy. A peri-gastric abscess was also drained. DISCUSSION: LVADs have revolutionized the management of advanced heart failure, however one-half of patients will develop a device-related infection within nine months of implantation. Although less common, GI-related LVAD infections, including enteric erosion and fistula formation, require a high index of suspicion. Non-invasive testing is suboptimal given limitations of current imaging modalities. Therefore, these patients should undergo upper and lower endoscopy for direct visualization and timely diagnosis.
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