Immune System “Fingerprinting” A Key to Understanding Autoimmunity

A recent study published in the journal Arthritis and Rheumatology, shows that the prevalence of antinuclear antibodies (ANA)– the most common biomarker of autoimmunity–has increased considerably in the United States in recent years.

Researcher Gregg E. Dinse and colleagues at Social & Scientific Systems, Durham, NC, examined the prevalence of ANA positivity in human subjects from three distinct time periods between 1988 and 2012. In total, they had data from 14,211 individuals.

The findings were astounding. Based on their sample population, they estimated that:

· In 1988-1991, 11% of the US population, or 22 million individuals, were ANA-positive.

· In 1999-2004, this increased to 11.5%, or 27 million individuals.

· In 2011-2012, the number was 15.9%, or 41 million individuals.

The authors note that prevalence of ANA increased in both genders over the last 30-plus years, but particularly in men. There were also marked increases in adults aged 50 years or older of all racial and ethnic backgrounds, and in non-Hispanic whites (Dinse GE, et al. Arthr Rheumatol. 2020).

“These increases in ANA prevalence were not explained by concurrent trends in weight (obesity/overweight), smoking exposure, or alcohol consumption,” they write.

As a category, “Autoimmune Disease” includes over 100 debilitating conditions; it is no wonder so many people are affected. The article also emphasizes the need for clinicians to take a more comprehensive look at the individual, immune system “fingerprints” of patients with autoimmune conditions. 


The immune system “fingerprint,” or “immunophenotype” as it is known in research terms, reflects an individual’s immunologic makeup, and it has significant implications in terms of how the immune system functions both in relation to the body’s own tissues, as well as in response to exogenous pathogens.  

Immunophenotyping uses highly specific antibodies to identify various types of cells based on the antigens and markers expressed on their surfaces, in their nuclei, or in their cytoplasm. These techniques, based largely on flow cytometry, are widely used in basic immunological research, as well as in cancer research and oncology practice. They’ve enabled oncologists to identify and categorize certain types of cancer, particularly leukemias, with great accuracy.

The immune system “fingerprint,” or “immunophenotype” as it is known in research terms...informs how each individual may react, or is reacting, to an environmental antigen, like a virus. In the context of the COVID-19 pandemic, this sort of information is essential to helping immunocompromised patients protect themselves.

Flow cytometry utilizes light-scatter technology to detect and count specific cell types present in a mixture of cells. It is preferred by top researchers because of its quantitative accuracy and specificity.

Recently, however, interest in the technique has extended well beyond basic research labs and oncology centers.

That’s because these tests can give physicians much more detailed information about a patient’s immune system than we can obtain from standard Complete Blood Count (CBC) panels. We can gain unprecedented, in-depth views of our patients’ immune systems. This knowledge is critical to making informed clinical decisions.

Relevance for COVID Risk

Immune system fingerprinting has relevance to the current COVID-19 pandemic.

We know that patients with autoimmune diseases are at higher risk for COVID-19. According to the Global Autoimmune Institute, there are instances in which having an autoimmune disease increases vulnerability to COVID-19 complications. In other cases, contracting COVID-19 triggers pre-existing autoimmunity, leading to symptom flares. Severe cases of COVID-19 have been associated with hyperactive immune responses in chronically ill patients, as well as those who previously showed no signs of autoimmunity.

A pre-existing, but possibly undetected issue with the immune system may enable the SARS-CoV-2 virus to move from the nose and throat, into the lungs, and to spread to other parts of the body.

Immunocompromised patients may not be able to manufacture the antibodies needed to prevent the virus from entering cells. Likewise, individuals on immunosuppressive medications such as corticosteroids are also at higher risk to be infected and suffer more severe COVID-19 complications.

We live in an ever-changing world of complicated novel pathogens, such as COVID-19. While it is important that we research and understand each of them, we must also recognize that there is much more to the complex picture of an individual patient’s risks and outcomes.

Simplifying a Complex Picture

As Hen-Avivi and Avraham note in their 2018 paper, “There is, in fact, great heterogeneity in infection outcome, from complete clearance of the pathogen to severe illness. Understanding this variation remains elusive, despite its great potential to equip us with new tools for the treatment of infectious diseases.”

A pre-existing, but possibly undetected issue with the immune system may enable the SARS-CoV-2 virus to move from the nose and throat, into the lungs, and to spread to other parts of the body

They propose that single-cell analysis technologies and recent advances in single-cell RNA-seq technologies “allow the detection of rare subpopulations that play important roles in host-pathogen interactions.”  These techniques can provide “a ‘fingerprint’ of the immune cell types that are associated with the ability of the host to clear a pathogen and, thereby, broaden our current understanding of variation in susceptibility to infection within the population.” (Hen-Avivi S, Avraham R. Curr Opin Microbiol. 2018).

In the clinic, immunophenotyping can give us a lot of information about the integrity of a patient’s immune systems. It goes far beyond what we can obtain from standard lab tests, which are not specific-enough or sufficiently detailed to allow a thorough evaluation of a patient’s overall immune system health or the risks of future diseases and complications.

Beyond the CBC

For example, unusually high or low white blood cell (WBC) counts obtained from a complete blood count (CBC) may indicate that something is wrong, but they do not usually reveal what is going on with the patient. Often, a CBC comes back absolutely normal, but the patient could actually be suffering from immune system dysfunction, immunodeficiency, hyper-inflammation, autoimmunity, allergies, and hypersensitivities induced by environmental triggers.

Simply stated, a stand-alone CBC panel is only one piece of the puzzle. Tests that reveal various immunophenotypes can give us significantly more usable clinical information.

Flow cytometry actually separates and quantifies different types of cells by detecting unique markers present on the cell surface. It is much more specific than standard tests that attempt to quantify different immune cell types by measuring cellular products such as cytokines and other signaling substances.

Since lymphocytes make up 20-40% of an individual’s total white blood cells (WBCs), understanding the lymphocyte sub-populations (like TH1, TH2, CD4, CD8, TH17, Natural Killer Cells etc.) and their ratios is the foundation of a detailed immune system fingerprint.

This fingerprint informs how each individual may react, or is reacting, to an environmental antigen, like a virus. In the context of the COVID-19 pandemic, this sort of information is essential to helping immunocompromised patients protect themselves.

Cyrex Laboratories’ a clinical laboratory specializing in functional immunology and autoimmunity, has recently developed a proprietary test panel called The Lymphocyte Map – Comprehensive Immunophenotyping of Lymphocytes, that provides comprehensive information on an individual’s unique immune system fingerprint. The Lymphocyte Map is the latest release in Cyrex’ innovative line of tests geared toward assessing “immune health.” In essence, it translates a host of complex flow cytometry data into an immune health analysis report.

Given the wide prevalence of autoimmune conditions, and the ways that autoimmunity heightens risk for infectious diseases, it makes good clinical sense to consider running a Lymphocyte Map any time you would typically order a CBC. It can provide indispensable information for guiding treatment decisions, and it has the added benefit of helping practicing clinicians to better read and comprehend the current medical literature at a time of unprecedented interest in the immune system.


Chad Larson, NMD, DC, CCN, CSCS, holds a Doctor of Naturopathic Medicine degree from Southwest College of Naturopathic Medicine and a Doctor of Chiropractic degree from Southern California University of Health Sciences. He is a Certified Clinical Nutritionist and a Certified Strength and Conditioning Specialist with particular interest in advanced developments in the fields of endocrinology, orthopedics, sports medicine, and environmentally-induced chronic disease. Dr. Larson is an Advisor and Consultant on the Clinical Consulting Team for Cyrex Laboratories.

Mark. Engelman, MD, is the Director of Clinical Consulting for Cyrex Laboratories. He is also the Founder and President of the Engelman Health Institute. His career history includes 23 years as the director of St. Joseph’s Medical Center emergency department; and a term as President of the Maricopa County American Heart Association. He is also the Founder and CEO of AmeriMed American Hospitals in Mexico; and is known as an expert speaker on emergency medicine both nationally and internationally.

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