Guidelines for the Clinical Use of ANA and Related Specific Autoantibody Testing

2000, Volume 11, Number 2


David F. Keren, M.D.

In the past few years several studies have suggested that inflammation plays a role in atherosclerosis. Indeed, some authors now consider the process to be a low-grade chronic inflammation that may even be related to infections.

Enter C-reactive protein (CRP).

CRP has been the most reliable marker of early inflammation for a couple of decades. It is a hepatocyte-derived, 135,000 dalton nonimmunoglobulin protein that migrates in the gamma region. C-reactive protein derives its name from the fact that it reacts with the capsular polysaccharide of Streptococcus pneumoniae. It is one of the most reliable, objective measures of the acute inflammatory response, and has been recommended as a particularly strong indicator of bacterial infections. Recent studies even place quantification of C-reactive protein as superior to cytokine assays of interleukin-6, interleukin 1beta and tumor necrosis factor for detecting the presence of inflammation in intensive-care patients.

Formerly, assays for CRP had a sensitivity of about 5 mg/L. With these assays, the level CRP was detectable only during significant inflammation in most individuals. However, recently, high-sensitivity assays of CRP (hsCRP) have become available. These assays have allowed studies to be performed on the CRP levels of individuals who are apparently healthy. Several reports now indicate that CRP concentrations are elevated in individuals who are at high-risk of developing coronary artery and cerebrovascular events. Indeed, the elevated CRP may be found years before first detection of the vascular problems. In the Physician’s Health Study, men with greater than 2.11 mg/L had about 3 times the risk of suffering a heart attack compared with individuals with CRP less than 0.55 mg/L (the lowest quartile of scores).

When evaluating the hsCRP data, be aware that all methods are not the same. An article in the April issue of Clinical Chemistry compared the 4 available hsCRP tests. They found that at the level of 1.3 mg/L (an important level for detection) the variability (coefficient of variation) of these tests varied from as low as 3.1% to as high as 24%! At Warde Medical Laboratory, we have chosen the method with the lowest variation to provide the most sensitive and reproducible assay for this important evaluation.

Lastly, when patients have an unexpected rise in the CRP value, it is likely to be related to another process-such as an infection or injury. DonÕt forget, CRP is still the most sensitive indicator of inflammation in the clinical laboratory. When you have questions about an particular patient, please feel free to call us (800 876-6522), or even better, write to us at our web site (


  1. Koenig W, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men. Results from MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237-242.
  2. Ridker PM, et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998;98:731-733.
  3. Rifai N, et al. Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem 1999;45:2136-2141.
  4. Roberts, WL et al. Evaluation of four automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Clin Chem 2000;46:461-468.