Thorough characterization of preparations of these proteins, whether isolated from different individuals or from pools of donors,

has so far shown only the single protein sequences corresponding to their respective single functional genes (Vigushin et al., 1993 and Pepys et al., 1994). The single typical biantennary N‐linked oligosaccharide of human SAP is also invariant ( Pepys et al., 1994); human CRP is not glycosylated ( Vigushin et al., 1993). Thus no genetic ‘experiment of Nature’ is available DNA Synthesis inhibitor for the human pentraxins. Our drug CPHPC ( Pepys et al., 2002) which produces persistent 90-99% depletion of circulating human SAP for as long as it is administered, has led to no functional deficit or detectable adverse effect in 31 adults with systemic amyloidosis treated for up to 7 years ( Gillmore et al., 2010). Any role of human SAP must have been redundant in these individuals and in the 70 or so other adults subjected to SAP depletion so far, including healthy normal volunteers (unpublished), patients with Alzheimer’s disease ( Kolstoe et al., 2009) and patients with osteoarthritis (unpublished). No drug is yet available which depletes CRP

although our novel bis‐phosphocholine compounds ( Pepys et al., 2006) are in development for clinical testing (www.pentraxin.com). The first GMP grade preparations of isolated human SAP and CRP which we report here are approved by the UK MHRA for administration respectively to patients and to human volunteers. SAP deficiency produces no abnormal phenotype in unchallenged mice, and since sustained almost Alectinib mouse complete SAP depletion in human patients with systemic amyloidosis,

Quinapyramine osteoarthritis or Alzheimer’s disease has had no adverse effects, we consider it neither necessary nor ethical to investigate the effects of large doses of isolated human SAP in volunteers. Our use of pharmaceutical grade SAP is thus confined to routine clinical SAP scintigraphy in the National Amyloidosis Centre, where the dose is 50-100 μg per patient and over 15,000 studies have been conducted since 1988, including over 10,000 with the present GMP preparation, without any adverse effects. In contrast, infusion of recombinant bacterial CRP, derived from material which is grossly contaminated with endotoxin (Pepys et al., 2005) and which was purified only by a single gel chromatography procedure (Bisoendial et al., 2005), elicited a marked inflammatory reaction in healthy human volunteers and in patients (Bisoendial et al., 2005, Bisoendial et al., 2007a, Bisoendial et al., 2007b and Bisoendial et al., 2009). The authors ascribed these effects to human CRP and construed them as support for a pro‐atherogenic role of CRP. Our studies with authentic, highly purified human CRP, isolated from humans rather than from recombinant bacteria, and with very low endotoxin content, had no pro‐inflammatory effects either on cells in vitro or in mice in vivo ( Pepys et al., 2005).