Pathogens. The specificity of the SELDI-TOF mass spectrometry profile for IAI is suggested by the presence of the 10.8-kDa proteolytic fragment of IGFBP-1, which has not been described in other inflammatory conditions. During pregnancy, the decidua, fetal membranes, and amniotic fluid are rich sources of IGFBP-1. Thus, the presence of the unique IGFBP-1 proteolytic fragment together with the presence of calgranulins is consistent with intrauterine infection in all cells. However, in atherosclerotic tissue, its expression is markedly up-regulated, and the inflammatory mediators produced by its activation exert various atherogenic effects. In this study, we evaluated whether the prevalence of the TLR4 genotype may have an association with acute myocardial infarction (AMI) and with longevity. Methods. We studied 105 young Sicilian men (mean age 41 years; range 20-46 years) consecutively admitted for AMI to the cardiac unit of Palermo University Hospital. Current smoking was present in 74% (former and current in 89%), family history of CVD in 58%, type 2 diabetes in 17%, obesity in 34%, hypertension in 29%, hypercholesterolemia in 61%, and hypertriglyceridemia in 43%. We used pooled maternal serum samples to ascertain the possibility of detecting calgranulin B and IGFBP-1 proteolytic fragment noninvasively without an amniocentesis. In biomarker discovery, pooled samples are frequently used to optimize detection of potential biomarkers. We agree that larger prospective trials that test serum samples from patients are necessary to confirm our findings. One control group consisted of 127 Sicilian men matched by age strata (mean age 38 years; range 20-50 years). These were students and staff personnel who were judged to be in good health based on their clinical history and on blood tests (complete blood cell count, erythrocyte sedimentation rate, and levels of glucose, blood urea nitrogen, creatinine, electrolytes, C-reactive protein, liver transaminases, iron, proteins, cholesterol, and triglycerides). Of these young controls, 20% were moderate smokers; no other major cardiac risk factor was present. A second control group consisted of 55 Sicilian oldest old men (mean age 100 years; range 96-104 years). By using the demographic lists of the registry offices of Palermo and surrounding municipalities, 166 potentially eligible oldest old men were identified in the Palermo area. Ninety-one (55%) agreed to participate. The control group was composed of the 55 (60%) who did not have any cardiac risk factors or major age-related diseases (eg, coronary heart disease, severe cognitive impairment, severe physical impairment, clinically evident cancer or renal insufficiency), although some had decreased auditory and visual acuity. Because immigration and intermarriage in Sicily have historically been rare, the Sicilian ethnicity of all participants was confirmed by having all four grandparents born in Sicily. The study was approved by the hospital ethics committee and written informed consent was obtained from all participants. Financial Disclosure: Drs Gravett and Nagalla are the founders of ProteoGenix and retain stock options in the company. 1. Heine RP, Weisenfeld H, Mortimer L, Greig PC. Amniotic fluid defensins: potential markers of subclinical intrauterine infection. Clin Infect Dis. 1998;27:513- 2. Searle BC, Dasari S, Turner M, et al. High-throughput identification of proteins and unanticipated sequence modifications using a mass-based alignment algorithm for MS/MS de novo sequencing results. Anal Chem. 2004;76:2220-2230. 3. Vogl T, Propper C, Hartmann M, et al. S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J Biol Chem. 1999;274:25291-25296. 4. Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003;24:155-158. 5. Hills FA, Gunn LK, Hardiman P, Thamaratnam S, Chard T. IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery. Early DNA was genotyped for the +896 A G (Asp299Gly) TLR4 single-nucleotide polymorphism (SNP) according to published methods. The Asp299Gly SNPIn the July 28, 2004, issue of JAMA (2004;292:462-469), a financial disclosure was omitted. Oregon Health and Science University (OHSU) investigators, including Drs. Gravett, Rosenfeld, Reddy, Jacob, Roberts, and Nagalla and Mr. Turner, have significant financial interests in Proteogenix Inc., a company that may have a commercial interest in the results of this research and technology. Among the three investigators involved in statistical analysis of the study (Drs. Gravett, Lapidus, and Hitti), the latter two have no potential financial interest in the results of this research. This potential conflict of interest has been reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee, and the Integrity Program Oversight Council has been implemented. Carmela Rita Balistreri, ScD; Giuseppina Candore, PhD; Giuseppina Colonna-Romano, ScD; Domenico Lio, MD Immunosenescence Unit Department of Pathobiology and Biomedical Methodologies University of Palermo Palermo, Italy 2340 JAMA, November 17, 2004 Vol 292, No. 19 (Reprinted)