Soluble Membrane Attack Complex: Biochemistry and Immunobiology.

The soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin. sMAC is a member of the MACPF/cholesterol-dependent-cytolysin superfamily of pore-forming molecules that insert into lipid bilayers and disrupt cellular integrity and function. sMAC is a unique complement activation macromolecule as it is comprised of several different subunits. To date no complement-mediated function has been identified for sMAC. sMAC is present in blood and other body fluids under homeostatic conditions and there is abundant evidence documenting changes in sMAC levels during infection, autoimmune disease and trauma. Despite decades of scientific interest in sMAC, the mechanisms regulating its formation in healthy individuals and its biological functions in both health and disease remain poorly understood. Here, we review the structural differences between sMAC and its membrane counterpart, MAC, and examine sMAC immunobiology with respect to its presence in body fluids in health and disease. Finally, we discuss the diagnostic potential of sMAC for diagnostic and prognostic applications and potential utility as a companion diagnostic.

Epidemiology of lumbar punctures in hospitalized patients in the United States.

OBJECTIVES: Lumbar puncture (LP) is an important technique for assessing and treating neurological symptoms. The objective of this study was to describe the characteristics of diagnostic lumbar punctures performed on hospitalized patients in the United States. METHODS: We analyzed data from the 2010 National Inpatient Sample (NIS) and the National Emergency Department Survey (NEDS). We included patients treated in the Emergency Department (ED) as well as those admitted to an inpatient bed through the ED. We identified patients undergoing LPs from ICD-9 procedural code 03.31 and CPT code 62270. We generated nationally weighted estimates of the total number of LPs. We also assessed patient and hospital characteristics of cases undergoing LP. RESULTS: Of an estimated 135 million hospitalizations (ED + admission, or ED only), there were an estimated 362,718 LPs (331,248-394,188), including 273,612 (251,850-295,375) among adults and 89,106 (71,870-106,342) among children (<18 years old). Of the 362,718 LPs, 136,764 (122,117-151,410) were performed in the ED without admission. The most common conditions associated with LP among children were fever of unknown origin, meningitis, seizures and other perinatal conditions. The most common conditions associated with LP among adults were headache and meningitis. CONCLUSIONS: Lumbar Puncture remains an important procedure for diagnostic and therapeutic uses in United States Hospitals.

Soluble membrane attack complex in the blood and cerebrospinal fluid of HIV-infected individuals, relationship to HIV RNA, and comparison with HIV negatives.

The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV+ adults (12 of whom underwent a second visit at least 24weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV+ individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV+ individuals on cART compared to HIV negative controls. In HIV+ participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance.