Many autoantibody tests for pathological autoantibodies yield a significant number of positive results in asymptomatic controls. So, a positive test does not diagnose an autoimmune disease! This type of positivity can be different than the positivity of natural autoantibodies (NAA) which are present as an essential constituent of a normal, intact immune system (such as the red blood cell anti-A and anti-B found in the serum of persons with blood group O type). NAAs include: antinuclear, antimitochondrial, anti-SSA-Ro, anti-IgG (rheumatoid factor), antithyroglobulin, antimicrosomal, antilymphocyte, antiactin (smooth muscle). There is pathologic potential for some NAAs, and they more likely represent a reflection of an antibody related pathological condition when the titer is high (this is why the screening of serum is usually with patient's specimen diluted 1:10)...and certain NAAs must be positive at even higher levels to be truly clinically significant.

• History & physical exam: The clinician should search for evidence of an immunodeficiency disease and any possible immune dysfunction.  He or she should then inquire about family history of diseases of immune pathogenesis, such as thyroiditis, systemic lupus erythematosus (SLE), myasthenia gravis, and so on.  The clinician also should look for the coexistence of other diseases, such as tumors, because there is an increased incidence of autoimmune diseases in patients with neoplasms.  A thorough physical examination...for enlarged thyroid glands, enlarged lymph nodes, arthritis, skin lesions, and so on...is critical.

• Lab findings that may indicate autoimmune an disease:

  • abnormal serum proteins by SPE or other methods

    • Anemia with increased reticulocytosis may suggest autoimmune hemolytic anemia.

    • Proteinuria and casts may indicate glomerulonephritis with immune pathogenesis.

    • Hypogammaglobulinemia may indicate an immunodeficiency disorder.

    • Elevated gamma globulin may indicate a wide variety of diseases, such as autoimmune liver disease or chronic systemic rheumatic disease.

    • An abnormal liver profile with elevated gamma globulin may indicate chronic viral hepatitis and/or autoimmune liver disease.

    • Hypertriglyceridemia may indicate an endocrine disease, such as Hashimoto's thyroiditis.

    • Hyperglycemia is a classic feature of diabetes.

  • elevated ESR or CRP

• Immunologic markers of autoimmune disease:

  • High level of serum gamma globulin

  • Demonstration of autoantibodies in serum

  • Demonstration of immune deposits in tissues

  • Accumulation of lymphoid cells involved in the autoimmune process in the tissues

  • Response to corticosteroid and immunosuppressive drugs

  • Association with other autoimmune diseases, which may coexist in the patient or occur within his or her family

  • Biologic false-positive serologic test for syphilis (may be associated with SLE)

• Classification of autoimmune disease: There are numerous ways to classify the autoimmune diseases.  However, the most useful and practical categories are the following: endocrine organ-specific autoimmune diseases, systemic autoimmune diseases, organ systemic diseases, and other autoimmune diseases.

References:

1. Nakamura RM, et. al., Clinical and Laboratory Evaluation of Human Autoimmune Disease, ASCP Press 2002, 450 pages.

(posted 12 August 2003; latest additions 29 September 2003)