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Our Tests Autoimmune Diseases

Autoimmune diseases can arise when the immune system malfunctions and forms “self-antibodies” (auto-antibodies) that attack normal, healthy tissues in the body. There are two general types: organ-specific, where the autoantibodies attack a specific organ (e.g., Hashimoto’s thyroiditis), and systemic, where multiple organ systems are involved [e.g., systemic lupus erythematosus).

Why our immune system malfunctions is not completely understood. It is thought that genetic susceptibility and a triggering event (e.g., a virus or a change in hormonal balance) together initiate production of autoantibodies that over time create clinical symptoms (this process can take several years). The development of autoimmune disease is a multifactorial process involving immune system derailment that is often precipitated by intestinal dysbiosis and damage to the gut lining.

 

Systemic Autoimmunity

Immune system dysregulation can lead to autoantibodies directed against a variety of intracellular antigens, such as chromatin (dsDNA and histones), nuclear/nucleolar proteins, centromeres, RNA, cytoplasmic organelles, and cell membrane components.1,2 These “antinuclear antibodies” (ANA) are often present in patients with autoimmune diseases.

The ANA test is performed by indirect immunofluorescence assay (IIFA) using HEp-2 (human epithelial cancer) cells; the “gold standard” method with high sensitivity to detect ANA present in serum.2,3 The specific staining pattern and titer of antibody binding, in conjunction with patient clinical symptoms, helps in differential diagnosis of autoimmune diseases such as systemic lupus erythematosus (SLE), Sjödren’s syndrome, scleroderma (systemic sclerosis), mixed connective tissue disease (CTD), rheumatoid arthritis, autoimmune liver diseases, and dermatopolymyositis.1,2,4,5

  •  An extractable nuclear antigen (ENA) panel may be used as follow up to a positive ANA test to identify the specific cellular component that is causing immunoreactivity and establish the correct diagnosis (testing for anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, anti-Jo-1, anti-dsDNA antibodies).1,2,3

As many of the early symptoms of autoimmune diseases (e.g., disabling fatigue, joint pain, Raynaud’s phenomenon, immune thrombocytopenia, skin rash, myositis, fever, neurologic signs) are common to other chronic diseases, detection and quantification of ANA can provide pivotal diagnostic information: confirming a suspected autoimmune CTD, excluding CTD in patients with ambiguous clinical findings, monitoring disease activity.

However, serum ANA are detected in up to 18% of the general population and 25% of apparently healthy people, with titers that are higher in women and increase with age.11-14 ANA may also be seen in patients with organ-specific autoimmune disease (e.g., autoimmune thyroiditis, multiple sclerosis), cancer, and those taking certain commonly-used medications (e.g., some statins, NSAIDs, ACE inhibitors, and β-blockers).5,7,15,1 The dense-fine speckled pattern in isolation may distinguish ANA-positive “healthy” persons from those with CTDs.9-10 ANA test results should therefore be evaluated carefully in conjunction with clinical signs and symptoms.

As ANA arise several years before symptoms, their presence in apparently healthy patients may indicate subclinical autoimmunity and increased risk for future CTD.2,18 ANA detection facilitates the early identification and treatment of autoimmunity to help prevent, slow, or halt disease progression.19

  1. von Muhlen CA, Tan EM. Semin Arthrit Rheum 1995;24(5):323–358.
  2. Agmon-Levin N, et al. Ann Rheum Dis 2014;73:17–23.
  3. Chan EKL, et al. Front Immunol 2015;6:Article 112.
  4. Soto ME, et al. Results Immunol 2015;5:13–22.
  5. Volkmann ER, et al. South Med J 2012;105(2):100–104.
  6. Mongey AB, Hess EV. Nat Clin Pract Rheumatol 2008;4(3):136–144.
  7. Conrad K, et al. Clinic Rev Allerg Immunol 2016;Jun 28. [Epub ahead of print]
  8. Mariz HA, et al. Arthritis Rheum 2011;63:191–200..
  9. Elnady BM, et al. Medicine (Baltimore) 2016;95(38):e4336. 2016;37(5):439–452.
  10. Arbuckle MR, et al. N Engl J Med 2003;349(16):1526–1533.
  11. Finckh A, Deane KD. Rheum Dis Clin North Am 2014;40(4):771–785.

 

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting up to 1% of us as we age.1 It is characterized by chronic inflammation of the joints and progressive destruction of bones and cartilage. Stiff, painful, and swollen joints can significantly impair quality of life. Early diagnosis and treatment is important.

Diagnosis of RA is based primarily on clinical signs and symptoms and the presence of specific autoantibodies in the blood. Detection of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibodies can confirm clinical diagnosis and help in predicting risk of disease development and gauging severity.2,3

Rheumatoid Factor: RF is an autoantibody against the conserved (Fc) portion of immunoglobulin G (IgG). Although it is a widely used serological marker for the diagnosis of RA and present in 60-90% of patients with established RA, RF is only present in about 50% of patients with early-stage RA and it can be detected in patients with other rheumatic disorders.3 RF can also be detected in 5% of healthy individuals, and in 10-30% of the elderly.2

Anti-Cyclic Citrullinated Peptide (CCP) Antibodies: Postranslational modification of the amino acid arginine to citrulline occurs naturally in the body, marking proteins for degradation during cell growth and turnover. While most people can readily clear the citrullinated proteins, those genetically predisposed to RA cannot, leading to the production of autoantibodies and inflammation.2,4 Anti-CCP is a highly specific early marker for RA and a powerful predictor of disease course.2,4,5 Positive anti-CCP results can confirm a diagnosis of RA, especially where RF is negative.6  The antigen used in the Salveo DiagnosticsTM anti-CCP test is the newest, most sensitive, 3rd generation CCP3.1 peptide that detects IgA and IgG antibodies.7 This is the only assay approved by the American Food and Drug Administration (FDA) for the early detection of RA.8

Uric Acid: Uric acid is a byproduct of purine nucleotide metabolism. Excess serum uric acid can cause crystals to form in the joints and other tissues. In genetically predisposed individuals, this may lead to inflammation and gout—a painful, chronic form of arthritis. High uric acid levels are also a risk factor for cardiovascular disease.9

The upregulated immune response–inflammation cycle characteristic of autoimmune diseases can cause chronic tissue damage over time. However, early treatment of RA or gout can alleviate inflammation, slow damage to the joints, and improve clinical outcome.

  1. Rheumatoid Arthritis Facts and Statistics. Rheumatoid Arthritis Support Network. Last Edited: August 3, 2016. https://www.rheumatoidarthritis.org/ra/facts-and-statistics/
  2. Taylor P, et al. Autoimmune Dis 2011;815038. (8)
  3. Sun J, et al. Clin Exp Rheumatol 2014;32:11-21.
  4. Van Venrooij WJ, et al. Ann NY Acad Sci 2008;1143:268-285.
  5. Jilani AA, et al. Int J Rheumatol 2015;2015;728610.
  6. Aletaha D, et al. Arthritis Rheum 2010;62:2569-2581.
  7. Vos I, et al. Clin Rheumatol 2017;36:1487-1492.
  8. Infantino M, et al. Clin Chim Acta 2014;436:237-242.
  9. Singh JA. Ann Rheum Dis 74(4):631-634.

 

General Immune Function

Immunoglobulins are proteins produced by cells of the immune system in response to bacteria, viruses, and other microorganisms or any substance that is recognized by the body as “non-self” and therefore potentially harmful. This test measures the amount of immunoglobulins G, A, M, and E (IgG, IgA, IgM, IgE) in the blood.

IgG is the predominant circulating immunoglobin, present in the plasma as well as interstitial body fluids. IgA, as a mucosal immunoglobin, plays a role in the development and maintenance of mucosal immunity in the gastrointestinal and respiratory tracts. IgM is usually the “first responder” to foreign antigens and plays an important role in the development of the immune response. IgE has traditionally been associated with atopic disease (allergy) and systemic anaphylaxis. It also plays a role in host defense, parasitic infections, and immune surveillance.

Testing for these antibodies provides important information about the health of an individual’s immune system and is used to help diagnose various conditions and diseases that affect the levels of one or more of these Ig classes.