High Anti-phosphorylcholine Antibody Levels and Mortality Associated with Pneumonia

Abstract

Phosphorylcholine is an immunodominant determinant of pneumococcal teichoic acids. Antibodies to phosphorylcholine are naturally occurring in man and decline in amount with age. Since antibodies to phosphorylcholine are markers of the immune responsiveness to polysaccharides and since anti-polysaccharide antibodies are highly protective against most bacterial pneumonia we expected a higher rate of pneumonia in elderly individuals with low levels of antibodies to phosphorylcholine. The relationship between the levels of antibodies to phosphorylcholine and mortality was analyzed prospectively in a representative sample of elderly individuals. A significant anti-phosphorylcholine antibody response occurred in a subgroup of the probands. There was a strong association (p less than 0.0001) between high levels of antibodies to phosphorylcholine in the serum at 70 years of age and pneumonia related death up to 14 years later. A similarly strong association was not observed between mortality and the antibody titer to another naturally occurring polysaccharide antigen: the blood group B antigen. Furthermore, there was no association between mortality due to diseases other than pneumonia and the levels of antibodies to phosphorylcholine. The association between antibody levels and subsequent fatal pneumonia provides a means of detecting individuals at risk for pneumonia-related death.

Crossreactivity of Human Anti-dsDNA Antibodies to Phosphorylcholine: Clues to Their Origin

“…Antibodies to PC are found to occur naturally in humans and decline in titre with age. A strong association between the mortality rate of pneumonia in elderly patients and titre of antibodies to PC has been observed [11]. Human anti-PC antibodies are predominantly of the IgG2 isotype presumably reflecting their origin in a T-independent antibody response, although in some individuals IgG1 and IgG3 isotypes have been found [12].…”

Bacterial Phosphorylcholine Decreases Susceptibility to the Antimicrobial Peptide LL-37/hCAP18 Expressed in the Upper Respiratory Tract

“…The predominance of the ChoP ϩ phenotype in the human respiratory tract was an unexpected finding, since ChoP renders the organism sensitive to killing by at least two mechanisms. There is activation of the classical pathway of complement mediated by both the abundant naturally acquired antibodies recognizing ChoP and Creactive protein (CRP), which binds specifically to ChoP (6,24,38). The selection for the ChoP ϩ phenotype in vivo despite the targeting of this structure by innate and adaptive immune mechanisms again emphasized that ChoP must confer advantages for bacterial survival.…”

Opsonization of Actinobacillus actinomycetemcomitans by Immunoglobulin G Antibody Reactive with Phosphorylcholine

“…Phosphorylcholine (PC) is the immunodominant epitope found in pneumococcal C polysaccharide (12,18) and an antigen present in normal mammalian cells. It has been shown to occur in a variety of gram-negative and gram-positive bacteria (7), as well as in up to one-half of the microorganisms in subgingival and supragingival dental plaque (15).…”

“…It has been shown to occur in a variety of gram-negative and gram-positive bacteria (7), as well as in up to one-half of the microorganisms in subgingival and supragingival dental plaque (15). Antibodies to PC are routinely found in human serum in the range of 30 to 300 g/ml (3,10,12,15). The function of these antibodies is unclear.…”

“…In mice, the induction of anti-PC antibodies is protective against lethal infections with Streptococcus pneumoniae (2); however, it has been reported that no correlation exists between anti-PC levels and protection against human S. pneumoniae infections in elderly patients (8). Additionally, serum fractions containing anti-PC are not opsonic for S. pneumoniae, and multivalent pneumococcal vaccines containing various amounts of PC fail to induce a significant antibody response against PC (9,11,12).…”