The Anti-Polymer Antibody Assay, or APA Assay, detects an abnormal immune system response in most fibromyalgia patients. In one preclinical study, the titers of the antibodies detected correlated with nine separate clinical measures of fibromyalgia severity, including:

• fatigue
• stiffness
• anxiety
• depression

The APA Assay appears to be the first practical laboratory test for fibromyalgia, and the correlation between antibody titers and symptomatology appears to provide the first direct evidence that fibromyalgia syndrome is in fact a unique disease which is based on a physiological, and not a psychological, pathology. Choose from the links below:

• INTRODUCTION
• THE RESEARCH STUDIES
• FREQUENTLY ASKED QUESTIONS (FAQ's)

INTRODUCTION

The APA Assay has been shown in two previously published studies to detect anti-polymer antibodies in the blood of a large percentage of patients with fibromyalgia and fibromyalgia-like symptoms. New data presented in September 2001 at the International Myopain Society's 5th World Conference on Myofascial Pain and Fibromyalgia revealed statistically significant relationships between the titers of these antibodies and nine different clinical measures of fibromyalgia severity.

The data presented in September 2001 was obtained from a study of well-characterized fibromyalgia patients which was conducted at the University of Texas Health Science Center in San Antonio (the "San Antonio study"). The San Antonio investigators were Yang-Ming Xiao, M.D., Ph.D., I. Jon Russell, M.D., Ph.D., and Joel E. Michalek, Ph.D. Dr. Russell is one of several world-recognized fibromyalgia experts, and Dr. Michalek is the principal investigator for the Air Force Ranch Hand Study, which is the largest and longest-running epidemiological study in the United States. Manuscripts describing the San Antonio study are now being prepared for publication.

The APA Assay appears to be the first practical blood test for fibromyalgia. Data from the San Antonio study is now being used to prepare clinical testing protocols to propose to the U.S. Food and Drug Administration as part of the process of winning FDA approval of the APA Assay as a diagnostic test for fibromyalgia. The published results suggest that the APA Assay may objectively contribute to distinguishing between patients with fibromyalgia and patients with connective tissue diseases such as systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, rheumatoid arthritis, and poly/dermatomyosis.

In part because of the historical absence of laboratory evidence to the contrary, many physicians currently feel that fibromyalgia is not a physically-based illness. These physicians instead believe that fibromyalgia is either a psychological disorder or that fibromyalgia symptoms are the product of some other disease which has not yet been correctly diagnosed. By directly associating immune response with symptomatology, the APA Assay demonstrates that fibromyalgia is in fact a unique physical disorder, or, in lay terminology, "a real disease."

The data from the San Antonio study suggests that anti-polymer antibodies might play a direct role in the fibromyalgia disease process. Data from this study as well as the two previously published studies indicate that approximately two-thirds of primary fibromyalgia patients test positive for anti-polymer antibodies. Primary fibromyalgia syndrome is believed by many researchers to have more than one cause, and it is entirely possible that fibromyalgia patients who test positive for anti-polymer antibodies represent a very large and previously unrecognized group of fibromyalgia patients whose disease is the result of one particular cause.

Drugs which modulate a patient's immune response are frequently prescribed by physicians to help alleviate symptoms in autoimmune disease patients. The APA Assay shows that an abnormal immune response is present in most fibromyalgia patients, and physicians could choose to interpret this finding as an indication that such drugs might also be useful in treating fibromyalgia patients.

The titers of the antibodies detected by the APA Assay correlate with nine measures of severity of symptoms of fibromyalgia. In contrast, other immunological test results rarely show any correlation at all between antibody titers and symptoms in any rheumatic disease. Because such correlations can in fact be explored by using the APA Assay, the Assay may also prove to be a valuable aid to physicians who wish to monitor flare and other on-going conditions in their fibromyalgia patients.

THE RESEARCH STUDIES

An article published in the February 1999 issue of The Journal of Rheumatology(1) entitled "Anti-Polymer Antibody Reactivity in a Subset of Patients with Fibromyalgia Correlates with Severity" shows that 47% of patients with fibromyalgia and 61% of patients with severe symptoms of fibromyalgia were seroreactive on the APA Assay. The pain thresholds, as determined by dolorimeter scores, for seropositive patients in the study were significantly lower than those of seronegative patients, demonstrating that APA Assay reactivity correlates with severity of symptoms. No other reported laboratory measure has been found to correlate with severity of symptoms in patients with fibromyalgia.

An earlier study of a different group of patients with fibromyalgia-like symptoms showed similar results. In an article published in the February 15, 1997 issue of The Lancet(2) entitled "Use of Anti-Polymer Antibody in Recipients of Silicone Breast Implants," 68% of patients with advanced fibromyalgia-like symptoms exhibited APA Assay seroreactivity. The results of these two studies suggest that the presence of anti-polymer antibodies may serve as a laboratory marker for an illness that is the same or similar in both groups of patients. The APA Assay was also shown to be a very specific test, with a level of APA reactivity among patients known not to have any fibromyalgia symptoms of approximately 3%.

Both articles also present results showing that APA reactivity is markedly lower (p< 0.05) in patients with diffuse connective tissue diseases than in patients with fibromyalgia or fibromyalgia-like symptoms alone. Such connective tissue diseases include rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis/scleroderma, and it can be difficult, particularly in severe cases of fibromyalgia, to differentiate fibromyalgia from these diseases.

The San Antonio study data presented in July 2004 at the Sixth World Conference on Myofascial Pain and Fibromyalgia(3) is entitled "Anti-Polymer Antibodies Identify a Large Subgroup of Fibromyalgia Syndrome Patients." The conclusions recited in the abstract are as follows:

The APA Assay kit was highly reliable. Significantly higher anti-polymer antibody values were found in primary fibromyalgia syndrome patients than in healthy normal controls. These findings suggest that anti-polymer antibody testing may have identified a previously unrecognized subgroup of primary fibromyalgia syndrome patients. It seems reasonable to propose that anti-polymer antibodies may be important to the pathogenesis of that primary fibromyalgia syndrome subgroup.

In the San Antonio study, statistically significant correlations (p ≤ 0.05) were found between the optical densities of the ELISA test results (i.e., the antibody titers) and the following nine clinical measures of fibromyalgia severity:

In addition, the correlation between antibody titers and a tenth clinical measure of fibromyalgia severity approached statistical significance at p = 0.06. This tenth measure was ABDMPAIN, which represents the number of days in which abdominal pain was experienced during the last week(3),(4).

Anti-polymer antibodies have also been shown to belong to the IgG2 subclass of human immunoglobulins, a subclass of IgG composed of antibodies that typically recognize non-peptide antigens(5).

In the San Antonio study, APA seroreactivity was found in approximately 26% of the population of relatively healthy normal controls. Subsequent analysis revealed that the APA-positive members of the control group exhibited a statistically-significant (p ≤ 0.05) increase in pain sensitivity as measured by dolorimeter, which suggests that anti-polymer antibodies are present in individuals with mild manifestations of fibromyalgia. A high APA reactivity rate among individuals who consider themselves to be healthy corresponds with the high rate of subclinical fibromyalgia found in studies by Clauw(6) and by Wolfe et al(7), which approached 20% of the adult female population in the United States.

Anti-polymer antibodies were discovered at Tulane University Medical School, and the APA Assay and has been licensed to Autoimmune Technologies, LLC of New Orleans. The APA Assay is currently covered by U.S., European and Australian patents, and other patents are pending.

The APA Assay is now being manufactured in commercial ELISA kit form. Because the APA Test Kit is undergoing FDA clinical trials it cannot be distributed in the U.S., though it is available in other countries. Individual tests for anti-polymer antibodies can be conducted in nitrocellulose strip format by Autoimmune Technologies as a service to interested physicians and researchers for investigational use.

FREQUENTLY ASKED QUESTIONS (FAQ's)

Is the APA Assay the first laboratory test for fibromyalgia?

Answer: Yes. Until now there has not been a lab test that is specific for fibromyalgia. Research studies to date have shown that the APA Assay can identify between one-half and two-thirds of fibromyalgia patients tested.

What does the APA Assay detect?

Answer: The APA (Anti-Polymer Antibody) Assay detects IgG anti-polymer antibodies in human serum.

What are anti-polymer antibodies?

Answer: Researchers are still in the process of trying to fully understand the nature of these antibodies. However, published studies have recently reported that fibromyalgia patients with a higher level of anti-polymer antibodies in their blood have more severe fibromyalgia symptoms than patients with lower antibody levels. This makes the APA Assay a valuable fibromyalgia test even though the circumstances surrounding antibody production are not yet completely understood.

Why do anti-polymer antibodies occur in fibromyalgia patients?

Answer: Why anti-polymer antibodies occur is also not fully understood yet. However, this is not unusual, because it is also not fully understood why other abnormal antibodies occur in diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Nevertheless, detecting the presence of the other antibodies in RA and SLE patients is useful in aiding in the diagnosis, and sometimes the treatment, of those illnesses.

If my physician has already told me that I have fibromyalgia, could this test be of any use for me?

Answer: Yes it could. The test could objectively confirm your physician's diagnosis, and it might also help in determining your treatment. A positive result on the APA Assay means that a fibromyalgia patient's immune system is producing anti-polymer antibodies. This is the first evidence that an immune response is associated with fibromyalgia as it is with rheumatoid arthritis and lupus. Immune-modulating drugs have not been thought to be appropriate for fibromyalgia in the past, but now the APA Assay could lend considerable support to a physician's decision to prescribe these drugs for a fibromyalgia patient.

Are there other examples of lab tests for factors that are not completely understood?

Answer: Yes. One good example is the anti-nuclear antibody test, or ANA test, which is the most commonly used autoimmune screening test. Physicians order the ANA test approximately 25 million times per year worldwide and use the results to help diagnose and monitor their patients, yet researchers still don't fully understand why anti-nuclear antibodies are produced or what their significance is.

What about using other lab tests for fibromyalgia patients?

Answer: There are dozens of lab tests that physicians can order when they are in the process of examining a patient suspected of having fibromyalgia. However, these tests are not specific for fibromyalgia and they are usually ordered to help rule out other immune disorders. Many fibromyalgia patients have completely normal results on all of these other tests.

Is a lab test useful even if it doesn't detect something in every patient?

Answer: Yes, both positive and negative test results can supply valuable information, and many diagnostic tests don't operate in the 95% to 100% detection range. For example, the discovery of proteins called rheumatoid factors helped convince physicians that rheumatoid arthritis was a real disease instead of a psychological disorder, yet only about 70% of patients who receive a diagnosis of rheumatoid arthritis test positive for rheumatoid factors.

If I don't have the antibodies that the APA Assay detects, does that mean I don't have fibromyalgia?

Answer: No, people without anti-polymer antibodies can still have fibromyalgia. In research studies to date, up to two thirds of fibromyalgia patients tested positive on the APA Assay but the other fibromyalgia patients did not. This and other research indicates that there are several distinct subgroups of fibromyalgia patients, and fibromyalgia patients without anti-polymer antibodies probably belong to one of the smaller patient subgroups.

Has the APA Assay been approved by the U.S. Food and Drug Administration for use as a diagnostic test?

Answer: No, but the test is undergoing the clinical trials necessary to support a regulatory filing for FDA approval. For diagnostic tests, the FDA requires that tests be produced in kit form, and the kit is what the FDA approves and regulates. An APA Assay kit, in the Enzyme Linked ImmunoSorbent Assay (ELISA) microtiter plate format, has been developed for Autoimmune Technologies by Corgenix, Inc., and this kit is now being used in the U.S. clinical trials. The data obtained from these trials will then be submitted to the FDA in what is called a Pre-Market Approval, or PMA, application.

How long do clinical trials take?

Answer: Unlike drug trials, clinical trials of a non-invasive blood test like the APA Assay can be done Questionuickly, and the clinical trials of the APA ELISA Kit will probably take between six and nine months to complete. After that, the PMA application to the FDA will be submitted. If the FDA decides to approve the PMA, approval could come within six months to a year after the date of submission.

Can I have my blood tested for anti-polymer antibodies?

Answer: The APA ELISA Kit is designed to be distributed to the clinical labs which run the test when it is ordered by a physician. FDA regulations prohibit the use of a test kit in the U.S. while it is undergoing clinical trials and approval, but the kit is available to labs in other countries through the Corgenix international sales office in Peterborough, UK. For more information, contact:

Corgenix UK Ltd.
75 Broadway
Peterborough
Cambridgeshire, UK PE1 1SY
www.corgenix.co.uk
Telephone: +(44) 01733 296800
Fax: +(44) 01733 296809

Does my physician know about this test?

Answer: Your physician may not know about the APA Assay, and you may want to give him or her a printed copy of the APA Assay Science Summary. Click here to print out a copy of Science Summary of The Anti-Polymer Antibody Assay (APA Assay) and Fibromyalgia Syndrome" (PDF format).