The Occurrence During Acute Infections of a Protein Not Normally Present in the Blood

Abstract

In 1930 Tillett and Francis (1) found that in certain infectious diseases, notably lobar pneumonia, the serum obtained from patients during the acute stage of the illness yields a precipitate in the presence of dilute solutions of the C polysaccharide of Pneumococcus. In pneumonia the precipitation test is positive during the height of the disease and becomes negative shortly after the onset of recovery. Thus the precipitating action of the serum closely parallels the clinical course of the infection. Although the particular carbohydrate used as test reagent is derived from Pneumococcus, the presence of the active substance in serum is not limited to pneumococcal diseases but occurs in a number of other infections such as acute rheumatic fever, bacterial endocarditis, and staphylococcal osteomyelitis. Ash (2) confirmed and extended these findings and showed that the "C-reactive" substance is demonstrable in sera obtained from children during the acute stage of infections due to Gram-negative bacilli of the colon-typhoid group. In view of the observations cited above it is evident that the phenomenon is associated with a variety of acute pathological conditions and is not specific with respect to the inciting agent.In 1934 Francis and Abernethy (3) published a preliminary report on the occurrence in patients during the acute stage of pneumonia of a characteristic skin reaction following the intracutaneous injection of 0.1 mg. of the C carbohydrate. They showed that the skin reaction is correlated with the precipitating action of the serum in vitro. These results were later confirmed by Finland and Dowling (4). Recently Abernethy and Francis (5) using a more highly purified preparation of the C polysaccharide corroborated the earlier work and emphasized the striking agreement between the results of the serological and cutaneous tests. In all patients in whom the disease terminated in uneventful recovery they found that both the serum and skin tests were positive during the acute febrile period and became negative shortly after crisis. With the development of complications, the capacity of the skin and serum to react may persist or reappear. Only in fatal cases have the results of the serological and cutaneous tests failed to agree. In these instances it has been observed that the skin may fail to react although the active substance can be demonstrated in the blood at the time of death.In a subsequent paper (6) Abernethy reported the results of a study of the precipitation reaction with sera obtained from experimentally infected animals. He found that the serum of monkeys (Macacus cynomolgos) acutely ill with experimentalType II Pneumo-173

The Phosphocholine-binding Pocket on C-reactive Protein Is Necessary for Initial Protection of Mice against Pneumococcal Infection

“…-dependent manner (1)(2)(3). The binding specificity of CRP is for the phosphocholine (PCh) moieties present in PnC (4).…”

“…Pneumococci remain the most common cause of community-acquired pneumonia world-wide (20 -22). In humans, CRP is an acute phase protein; that is, its serum concentration is * This work was supported, in whole or in part, by National Institutes of Health increased several hundredfold in response to pneumococcal infection (2). However, the functions of CRP in pneumococcal infection are not known (3).…”

Application of acute phase protein measurements in veterinary clinical chemistry

“…The rapid sedimentation rate was later found to reflect elevated concentrations of several plasma proteins, in particular the acute phase protein (APP) fibrinogen [46,186]. The term "acute phase" was introduced in 1941 to describe serum in which another acute phase protein, the C-reactive protein, was present [1,109]. The acute phase response is now considered to be a dynamic process involving systemic and metabolic changes providing an early nonspecific defence mechanism against insult before specific immunity is achieved [148,170].…”

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

“…PTXs also trigger the complement system via the classical complement pathway through C1q Volanakis and Kaplan, 1974) and increase pathogen clearance via phagocytosis (Bharadwaj et al, 2001). Short-chain pentraxins are involved in acute-phase response (APR) and recognise various pathogenic bacteria or cellular debris in a characteristic calcium-dependent manner (Abernethy and Avery, 1941;Thompson et al, 1999). CRP binds primarily to phosphorylcholine (PC) (Narkates and Volanakis, 1982;Szalai et al, 1999), whereas SAP binds to amyloid fibrils and the cyclic 4,6-pyruvate acetal of b-D-galactose (Hind et al, 1984).…”