Immunology and Autoimmunity

Immunoglobulins (Antibodies)

Function to neutralize toxic substances, support phagocytosis, and destroy microorganism functions.

 IgA
o Serum – blood stream
o Secretory – saliva, tears, colostrum, bronchial, GI and GU secretions

Increased

 Primary biliary cirrhosis

 Obstructive jaundice

Decreased

 Protein-losing gastroenteropathies
 IgE
o Allergic reactions
 IgD
o Humoral immunity
 IgG
o The only immunoglobulin that can cross the placenta
o Responsible for protection of the newborn during the first months of life

Increased

 Rheumatoid arthritis
 Malnutrition

Decreased

 Bence Jones proteinemia

 Chronic lymphoblastic leukemia
 IgM
o Possess antibody activity against gram negative organisms and rheumatoid factors

Increased

 Infectious mononucleosis
 Lupus erythematosus

Decreased

 Lymphoproliferative disorders
 Chronic lymphoblastic leukemia
 Protein Electrophoresis

Serum proteins are a source of nutrition and a buffer system. Blood serum and urine are commonly screened for
monoclonal immunoglobulin component by SPEP and UPEP. In health, the immunoglobulins are polyclonal instead
of monoclonal. When a monoclonal band is observed it typically signals a neoplastic process.

Increased

 Multiple myeloma
 Waldenstrom’s macroglobulinemia
 Liver disease
 Systemic lupus erythematosus
 Rheumatoid arthritis

Decreased

 Malnutrition
 Nephrotic syndrome
 Crohn’s disease
 Ulcerative colitis

Immunofixation Electrophoresis

Monoclonal immunoglobulins consist of heavy and light chains. Immunofixation does two things, identifies the
presence of absence of monoclonal protein and determines its heavy-chain and light-chain types.

 Monoclonal protein suggests neoplastic process

 Polyclonal increase suggests chronic liver disease, connective tissue disease, infection

 Monoclonal light chain (K or Bence Jones protein) is found in the urine of patients with multiple myeloma

Cold Agglutinin

Diagnose primary atypical viral pneumonia caused by Mycoplasma pneumoniae and diagnose certain hemolytic
anemias.

C3 Complement Component

Constitutes 70% of the total protein in the complement system and is essential to the activation of both classic and
alternative pathways. Synthesized in the liver, macrophages, fibroblasts, lymphoid cells, and skin. This is useful for
assessing disease activity in SLE.

Decreased C3

 Acute poststreptococcal glomerulonephritis

 Active SLE
 Nephritis
  End stage liver disease

Increased C3

 Inflammatory states

C4 Complement Component

This is synthesized in the bone and lung tissue.

Decreased C4

 Acute SLE
 Early glomerulonephritis

Increased C4

 Malignancy

Antinuclear Antibody (<1:160)

Most commonly performed screening test for autoantibodies in patients suspected to have systemic rheumatic
disease. Examples of these include SLE, mixed connective tissue disease, Sjogrens syndrome, scleroderma, CREST
syndrome, rheumatoid arthritis, and polymyositis dermatomyositis.

Anticentromere Antibody

Anticentromere antibodies appear in about 90% of patients with CREST syndrome.

Anti-dsDNA Antibody

This is done to specifically identify or differentiate native DNA antibodies found in 40%-60% of patients with SLE
during the active phase of their disease from other, nonnative DNA antibodies found in other rheumatic diseases.

 Presence of antibodies to dsDNA generally correlates with lupus nephritis

 Supports a diagnosis of SLE
 Allows monitoring of disease activity and response to therapy in SLE
 Establishes a prognosis for SLE

Rheumatoid Factor

This is useful in the diagnosis of Rheumatoid Arthritis. RF is sometimes found in blood serum from patients with
other diseases.
 Cyclic Citrullinated Peptide Antibody

This test helps to diagnose Rheumatoid Arthritis. These are autoantibodies produced by the immune system that are
directed against CCP. Citrulline is naturally produced in the body as part of the metabolism of the amino acid
arginine. In joints with RA this conversion occurs at a higher rate.

Antibodies to Extractable Nuclear Antigens

 Anti-RNP
o Mixed connective tissue disease
 Anti-Sm
o SLE
 Anti-SSA (Ro)
o Sjogren’s syndrome
 Anti-SSB (La)
o Sjogren’s syndrome
 Anti-Scl-70
o Scleroderma
 Anti-Jo-1
o Polymyositis

Cardiolipin Antibodies

In patients with SLE, antibodies to cardiolipin have been associated with arterial and venous thrombosis,
thrombocytopenia, and recurrent fetal loss.

Gliadin Antibodies

Antibodies to gliadin (wheat protein) have been shown conclusively to be the toxic agent in celiac disease. IgG and
IgA gliadin antibodies are detected in sera of patients with gluten-sensitive enteropathy.

Antineutrophil Cytoplasmic Antibodies

Two types:

 cANCA is found in Wegener’s granulomatosis

 pANCA is found in systemic vasculitis

C-Reactive Protein

This appears in the blood during an inflammatory process in response to inflammatory cytokines. Virtually absent
from the blood of healthy persons. This is one of the most sensitive acute-phase reactants.

 CRP (0.3-20 mg/dL)

o Trauma, infection, inflammation, surgery, or neoplastic proliferation
 hs-CRP (0.1 mg/dL)
 o risk for developing myocardial infarction

Erythrocyte Sedimentation Rate

Sedimentation occurs when the erythrocytes clump or aggregate together in a column-like manner (rouleaux
formation). The ESR is the rate at which erythrocytes settle out of anticoagulated blood in 1 hour. The faster the
settling, the higher the ESR. This is based on the fact that inflammatory and necrotic processes cause an alteration in
blood proteins.

 Temporal arteritis
 Rheumatoid arthritis
 Polymyalgia rheumatica

Tumor markers

 Prostate specific antigen

o Carcinoma of prostate
 Lactate dehydrogenase
o Testicular cancer
o Ewing’s sarcoma
o Acute lymphocytic leukemia
o non-Hodgkin’s lymphoma
o Breast cancer
o Lung cancer
o Colon cancer
 Human chorionic gonadotropin
o Testicular cancer
o Ovarian cancer
 Calcitonin
o Breast cancer
o Thyroid cancer
 Serotonin (5-HIAA)
o Carcinoid tumors
 Alpha-fetoprotein
o Hepatocellular cancer
o Testicular cancer
o Pancreatic cancer
 Carcinoembryonic antigen
o Colon cancer
o Pancreatic cancer
o Lung cancer
o Stomach cancer
 CA 19-9
o Pancreatic cancer
o Colorectal cancer
 CA 125
o Ovarian cancer
o Endometrial cancer
 BRCA-1 and BRCA-2
o Predisposition to developing breast and ovarian cancer