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From the Townsend Letter
January 2014

Predictive Biomarkers in Personalized Laboratory Diagnosis and Evidence Based Best Practices Outcome Monitoring
by Russell Jaffe MD, PhD, CCN, and
Jayashree Mani, MS, CCN

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The LRA tests measure all three delayed allergy pathways (Figure 5) while avoiding false positives common in other types of delayed allergy tests:

  • reactive antibody (IgA, IgM, and IgG)
  • immune complexes
  • direct T-cell activation

The LRA by ELISA/CT tests are fundamentally different from antibody serology or particle counting tests in that ex vivo LRA tests are substantially more sensitive, specific, and predictive.
Benefits of the LRA compared with other allergy tests include that it is:
1. comprehensive: Only clinical tests of all three delayed allergy pathways at one time (type II, type III, and type IV) able to perform up to 491 cell cultures on just 1 ounce of blood;
2. functional: Identifies only symptom provoking reactive substances, not merely harmful or protective while missing T-cell responses entirely;
3. ex vivo: Unique LRA tests are performed just as they occur inside the body.
Identifying the patient's specific sensitivities and delayed allergies that burden the immune system is a clinical breakthrough. Patients often experience a dramatic improvement in quality of life as a result of the individualized treatment plan, which includes an alkalinizing diet and targeted supplementation. After 6 months, a reevaluation of progress is recommended with three possible outcomes:
1. If patient is in remission, a guided gradual reintroduction of previously reactive items 1 per week is advised, ingesting an item 3 times in the first week because of amnestic responses.
2. If patient is better but not yet well, repeat LRA tests and treatment guidance every 6 months until in sustained remission. Since digestion and detoxification, among other systems, take time to recover, it is common for people to lose some reactive items and acquire new ones. A repeat program starting from a healthier base is likely to further improve health and sustain remission.
3. If patient reports following instructions carefully and avoiding reactive items but is still not better, look for toxins or hormone-disrupters that might inhibit to recovery. If a person reports making best efforts at following the program and does not report improvement, repeat testing is not indicated.
Healthy immune tolerance means no delayed allergic LRA reactions. Highly healthy people are tolerant. People can restore tolerance as part of a proactive prevention lifestyle. If reactions are found by LRA tests, our approach includes substitution of reactive foods along with an Alkaline Way whole-foods diet with an emphasis on super-foods, targeted supplementation to promote repair, and mental and physical activities to evoke healing responses. LRA by ELISA/ACT cell cultures are reproducible within less than 3% when different readers read split samples on different days.

Discussion and Conclusion
The eight predictive biomarkers discussed here are presented for use in clinical practice based on their predictive goal value and translated into years or decades of life at risk, retainable, or recoverable. Every health practice can benefit from learning about the value of personalized medicine and effective proactive prevention.
While each of the predictive biomarkers is predictive, when four or more are interpreted together, their predictive power increases, covering the 92% of lifetime health determined by choice and habit. While each biomarker is a separate marker of certain aspects of physiology, human systems are interdependent and usually consistent. When a biomarker shows higher risk, sooner rather than later is the time to take action and bring that marker back to or toward the goal value.
By example, hemoglobin A1c is highly predictive of certain aspects of sugar, insulin, energy metabolism, weight, metabolic syndrome, diabetes, cardiovascular, and other chronic diseases. Hs-CRP is highly predictive for other aspects of cardiovascular and chronic disease, particularly in regard to repair deficits that present as clinically as inflammation and to the person as stiffness or pain. Homocysteine rounds out the remainder of cardiovascular risks as they relate to methylation, sulfur metabolism, detoxification, and epigenetic modulation.
Predictive biomarker goal values are best on best outcome and least risk variables that do not depend on age or gender. The usual or statistically normalranges for homocysteine, for example, are usually based on age and gender. This means that there are more unhealthy people in the population as it ages. Age-conditional usual lab ranges often drift toward the less well with advancing age. Age, however, is a contingent variable. The significant variable is how many unhealthy people are present at each age. An important difference: chronology is fixed and most of function is choice.
Every test has a standard deviation or range within which the value exists. Typical variance for most classic ELISA based tests is 20% or more. This means that a value of 6 from a given specimen will cluster values around 6 with a large range of values from 4.8 to 7.2. The typical lab test variance is 20%. The more narrow the variance, the more predictive is the observed value. For predictive biomarker tests, a variance of 5% or less is desirable. For example, if the "true" value is 6 and the test technology allows for better precision and as a result a 3% variance, a single test value actually exists between a narrow range of 5.92 and 6.18. Improvement in preanalytic variables by reducing interfering substances, improved control of analytic conditions, use of improved curve fitting particularly at the lower end of the test range, often where the accuracy of measurement is most important. As a result, the predictive significance of any specific value becomes much greater. Such improvements in precision have been accomplished in higher-complexity tests such as lymphocyte response assay cell cultures (e.g., LRA by ELISA/ACT). As with all tests and particularly homocysteine, attention to details makes for better clinical results and improved human outcomes, particularly when therapy or management is based on lab results. Colleagues such as Alan Gaby have long pointed out that the best of tests done poorly or whose meaning is misunderstood by practitioners is unhelpful to the client. Mark Twain summed up the issue as follows: "Be careful about reading health books. You could die of a misprint." Those of us who are clinical, analytical, methodological, and metrological have an obligation to point out strengths and limitations of tests where results drive therapies or predict outcomes.
Separately, two people, each with a true hemoglobin A1c of 8%, one of whom has been diagnosed as a diabetic, both have an equally high risk of a cardiovascular or other health crisis within 10 years. Technically, both are diabetic and only one knows it. This is known as the difference between incidence and prevalence. Many diabetologists today are increasingly diagnosing the degree of diabetes based entirely on accurately performed Hgb A1c tests.
While each of these tests is a predictive biomarker, when they are taken together we can identify both where healthier resilience exists and also where risks that can be reduced are identified. Predictive biomarkers are each based on large-scale, long-term studies including all ethnic, economic, and cultural groups. There are no population exceptions of which we know. The predictive goal value for the biomarkers explained here is based on evidence from many studies covering all ethnic groups over long periods of time in regard to all-cause morbidity and mortality; that is, life expectancy. The probability of living 10 years for these predictive biomarkers is based on large-scale, long-term community-based outcome studies. The Health Studies Collegium includes links to review articles that address aspects of predictive personalized and potentially life-saving tests and what to do about them.
Predictive biomarkers are not age adjusted, because the interpretations of the test results reported here are based on least-risk, best-outcome healthier goal values. Healthy people at all ages have the same lab ranges. As people accumulate age, there are more unhealthy people in each progressive decade. This is why using predictive biomarkers based on goal values is an advancement of the previous statistical normality approach.
While too many people live in denial about their health until some catastrophe occurs, more and more professionals and consumers are using predictive biomarkers to help assure and guide their lifestyles. These proactive consumers of healthier caring are likely to live well and prosper.

Functional predictive biomarkers can be obtained through
Link to the predictive biomarker table:
Clinical protocols for these eight predictive biomarkers can be obtained by contacting PERQUE Integrative Health: 800-525-7372;
ELISA/ACT Biotechnologies: 800-553-5472;
Health Studies Collegium: 800-328-7372;

1.  Galen RS, Gambino SR. Beyond Normality: The Predictive Value and Efficiency of Medical Diagnosis. New York: Wiley; 1975.
2.  Cheraskin E, Ringsdorf WM Jr, Clark JW. Diet and Disease. Emmaus, PA: Rodale Books; 1968.
3.  Williams RJ. Biochemical Individuality: The Key to Understanding What Shapes Your Health. New Canaan, CT: Keats Publishing; 1998.
4.  Hinzmann R, Schlaeger C, Tran CT. What do we need beyond hemoglobin a1c to get the complete picture of glycemia in people with diabetes? Int J Med Sci. 2012;9(8):665–681.
5.  Silva D, Pais de Lacerda A. High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease. Rev Port Cardiol. 2012;31:733–745.
6.  Jaffe R, Mani J. Rethink health: inflammation is actually repair deficit: using physiology first to achieve better outcomes, part 1: value and importance of understanding inflammation as repair deficit. Townsend Lett. 2013 Jun;359:68–74.
7.  Holvoet P, De Keyzer D, Jacobs DR Jr. Oxidized LDL and the metabolic syndrome. Future Lipidol. 2008 December; 3(6):637–649.
8.  Humphreys V, Martin RM, Ratliffe B, et al. Age-related increases in DNA repair and antioxidant protection: A comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample. Age Ageing. 2007;36(5):521–526.

Dr. Russell Jaffe received his AB, MD (with senior thesis honors), and PhD (In biochemistry and physiology) from Boston University. Dr. Jaffe served his medical internship at University Hospital and was awarded a the US Public Health Service Officer Commission, assigned to the Clinical Center of the National Institutes of Health, in June 1973. While at the Clinical Center, Dr. Jaffe served his residency in clinical pathology. He is board certified in clinical and subspecialty certified in chemical pathology. Dr. Jaffe remained on the permanent senior staff of the NIH Clinical Pathology Department, where he continued method innovation and was active in collaborative research with the Laboratory of Experimental Atherosclerosis (of the Heart, Lung, and Blood Institute). Concurrently, Dr. Jaffe's interests in the mechanisms of health and the evoking of human healing responses led him to apprentice in such healing arts as acupuncture; mindfulness; massage; music, art, and color therapy; and a variety of eclectic therapeutic approaches. In addition, Dr. Jaffe performed innovative studies of platelet function and blood clotting in relation to the origins of coronary artery and cardiovascular diseases. Among the tests that he developed are the early colon cancer-screening test using occult blood detection not interfered with by vitamin C consumption, as well as a variety of tests related to the blood clotting and immune defense and repair systems. Dr. Jaffe developed the first method of measuring cell-mediated immunity using a modified ELISA system in a lymphocyte mitogenesis/blastogenesis brief cell culture known as lymphocyte response assays (LRA). This LRA by ELISA/ACT provides an "immunologic fingerprint" of items to which the body is reactive or tolerant.

Dr. Jaffe has contributed over 100 symposium-invited talks, scientific articles, or book chapters. He received the J. D. Lane award for original research from the USPHS, the Merck Sharp and Dohme Excellence in Research Award, and in 2002 the International Research Scientist of the Year, among other recognitions for his investigations. Dr. Jaffe is a fellow of the Health Studies Collegium and director of ELISA/ACT Biotechnologies LLC and PERQUE LLC in Ashburn, Virginia. He may be reached at 800-525-7372 ext. 5101, and or

Jayashree Mani is a certified clinical nutritionist (CCN). She is experienced in the effective implementation of the comprehensive program described in this article involving these predictive biomarkers, LRA by ELISA/ACT tests, Health Appraisal Questionnaires (HAQ), Alkaline Way diet, and PERQUE nutraceuticals.

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