Diagnosis of Autoimmune Diseases: Laboratory Testing

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Diagnosis of Autoimmune Diseases: Laboratory Testing

Since autoimmune diseases can affect multiple organs and produce highly variable signs and symptoms that can change in severity over time, recognizing and diagnosing autoimmune diseases can be difficult. Signs and symptoms can be vague, slow to present, and cause incorrect diagnosis. In addition, laboratory tests used to diagnose autoimmune disorders often depend on the particular disorder suspected. Blood tests that indicate the presence of inflammation are usually performed to help diagnose an autoimmune disorder. When autoimmune disease is suspected, the common laboratory evaluation will serve as an initial red flag to pursue further testing. Initially, it is typical that one or more of the following laboratory tests may be performed:
Hematology
Characteristic findings on a complete blood count (CBC) can include normocytic, normochromic anemia indicating the chronicity or severity of a disease and an elevated or decreased platelet count and/or white blood cell count. Leukopenia and thrombocytopenia are common in patients with systemic lupus erythematosus (SLE). Some inflammatory conditions can lead to a slight microcytic, hypochromic anemia. Pernicious anemia, caused by an inability to absorb vitamin B12, is generally macrocytic.
Chemistry
Depending on the specific autoimmune disease, testing for serum levels of specific organ enzymes or abnormalities in metabolic processes may show an elevation of transaminases (ALT and AST), creatinine kinase, bilirubin, and other serum proteins (immunoglobulins).
Coagulation
Coagulation studies may show elevations in the activated partial thromboplastin time (aPTT) and/or the prothrombin time (PT), which could suggest an inhibitor of the clotting process as seen in certain autoimmune disorders such as antiphospholipid syndrome.
Urinalysis
In autoimmune disorders, the urinalysis is commonly used to assess renal injury (glomerulonephritis, interstitial nephritis) and can show proteinuria, hematuria, or clinically significant microscopic elements (e.g., white blood cell casts, red blood cell casts, waxy casts, fatty casts).
Inflammatory markers
Inflammatory markers are serum proteins that are produced in response to inflammation. These proteins are mainly produced by the liver in response to stress and are called acute phase reactants. These inflammatory markers are not diagnostic of inflammation but reflect abnormalities seen in autoimmune diseases, infections, malignancies, and other illnesses.
Several tests for specific protein markers can be employed to assess acute or chronic inflammation; however, none of these tests are necessarily specific for a given autoimmune disease. One or more of the following markers may be elevated in acute or chronic inflammation:
  • Ferritin
  • Ceruloplasmin
  • Haptoglobin
  • Albumin
  • Fibrinogen
Erythrocyte sedimentation rate (ESR)
The ESR, the measure of the rate that red blood cells (RBC) settle in a tube, is typically elevated in inflammation. Multiple factors can influence the ESR, including the patient's age, gender, RBC morphology, hemoglobin concentration, and serum levels of immunoglobulin. While the ESR is not a diagnostic test, it can be used to monitor disease activity and treatment response and signal that inflammatory or infectious stress is present.
C-reactive protein (CRP)
CRP (including high-sensitivity CRP) was discovered and named for its reactivity to the C polysaccharide in the cell wall of S. pneumoniae. CRP helps in the process of phagocytosis and activates the complement system. CRP production is controlled by cytokines IL-1, IL-6, and TNF-alpha. Changes in serum CRP concentration occur faster than ESR. Therefore, CRP may be a better reflection of current inflammation. Unlike the ESR, CRP is a fairly stable serum protein whose measurement is not time-sensitive and is not affected by other serum components. In addition, the magnitude of inflammation directly relates to the concentration of CRP. More recently, high-sensitivity CRP has been utilized and may better quantify lower levels of inflammation.