C5 PROTEINS & TUMOUR MARKERS PART 1

Plasma Proteins

  • two major groups: albumin & globulins

Individual plasma protein conc. affected by

  • nutritional status
  • physiologic changes
  • synthesis rate
  • extracellular distribution
  • clearance rate

▪ Total protein level remains relatively constant (reference range: 6.4 – 8.3 g/dL) ▪ Most synthesized in the liver, except immunoglobulins & protein hormones ▪ Prealbumin, albumin, α2-macroglobulin, ceruloplasmin, haptoglobin, transferrin, immunoglobulins, myoglobin, C- reactive protein, complement proteins and α1-antitrypsin

Prealbumin (Transthyretin)

▪ Small transporter protein that migrates before albumin in classic serum protein electrophoresis

▪ Transports thyroid hormones (i.e., T3 and T4)

▪ Also binds to retinol-binding protein for the transportation of vitamin A (retinol)

▪ Synthesized in the liver & choroid plexus of the central nervous system

→ stimulated by glucocorticoid hormones, androgens & NSAIDs

Laboratory Investigations

i) immunonephelometry

  • measure the intensity of light scattered from the sample by using laser light & nephelometer

ii) immunoturbidimetry

  • measure the intensity of light pass through the sample by using spectrophotometer

Clinical revelance for prealbumin

  • reference range: CSF: 0.0 – 3.1 mg/dL   Serum: 10 – 20 mg/dL
  • indicates protein nutrition
  • higher than normal: severe renal failure, corticosteroid use, oral contraceptive use
  • lower than normal: malnutrition, liver disease, serious infection, trauma, inflammation, serious or long term illness, hyperthyroidism

Albumin

  • small protein found in blood, CSF, interstitial fluid, urine & amniotic fluid
  • synthesized in the liver
    • stimulated by hormones, eg., insulin, cortisol & growth hormone
    • inhibited by proinflammatory substances, eg., IL-6 & TNF-alpha
    • regulated by colloidal osmotic pressure and protein intake
  • catabolized mainly in the muscles, liver & kidneys
  • Primary function: maintain the colloidal osmotic pressure in the intravascular & extravascular compartments
  • serves as a transport protein for fatty acids, phospholipids, cholesterol, amino acids, hormones, bilirubin, drugs, toxins, metallic ions & gas

Laboratory investigations

  • measured colorimetrically by using bromocresol green dye
  • upon binding to albumin at pH 4.2, bromocresol green
  • colour intensity is directly proportional to the amount of albumin present in the serum sample
  • interfere by high concentration of bilirubin, hemolysis, lipemia

Clinical Revelance

  • reference range: 3.5 - 5.2 g/dL
  • related to liver or kidney disease, or underlying nutritional deficits
  • hyperalbuminemia: dehydration, increased insulin level, blood transfusion, exogenous albumin administration, anabolic steroid use, androgen/ growth hormone administration
  • hypoalbuminemia: overhydration, hepatic disease, nephrotic syndrome, protein-losing states, inflammation, poor nutrition

 

  • serine protease inhibitor
    • inhibits different types of proteinases
    • inhibits enzymes in the kinin, complement, coagulation & fibrinolytic pathways
  • carrier proteins for cytokines, growth factors & cations
  • modulates immunologic & inflammatory reactions
  • very large glycoprotein synthesized mainly in the liver

Laboratory findings of alpha2-macroglobulin

  1. serum protein electrophoresis
    • one of the major proteins comprising the alpha2-globulin band
  2. immunologic assay
    • intensity of the light scattered onto the antigen-antibody complex is proportional to the amount of proteins (antigen) in the sample

Clinical Relevance of alpha2-macroglobulin

  • reference range: 150 - 420 mg/dL
  • increased level: nephrotic syndrome, related to estrogen & age
  • decreased level: acute phase response, pancreatitis, prostate cancer

Immunoglobins

  • function as antibodies
  • composed of 2 light protein chains & 2 heavy protein chains
  • produced by plasma cells in response to pathogenic antigens
  • constitute about 20% of the plasma proteins
  • 5 classes: IgG, IgM, IgA, IgD, IgE

IgG - neutralizes toxins, viruses and bacteria, opsonizes bacteria for phagocytosis, 800-1800mg/dL

IgE - least prevalent antibody, during an allergic reaction, the immune system overreacts by producing these antibodies, 0-160kIU/L

IgD - B cell antigen receptor, exact function is unknown, 0-384mg/ml

IgM - serves as the first line of host defense against infections, plays an important role in immune regulation and immunological tolerance, 60-250mg/dL

IgA - most abundant antibody, binds and neutralizes food allergies, protects mucosal tissues from microbial invasion, 90-450mg/dL

Laboratory investigations for immunoglobulins

  • reference range
    • IgG: 800-1800mg/dL
    • IgM: 60-250mg/dL
    • IgA: 90-450mg/dL
    • IgD: 0-384mg/dL
    • IgE: 0-160kIU/L
  • serum protein electrophoresis
  • immunoelectrophoresis/ immunofixation
  • immunoturbidimetry/ immunonephelometry

Clinical relevance

  1. Immunoglobulin deficieny
    • most manifest in infancy
    • those in adults are due to another primary disorder or immunosuppressive therapy
    • most common types: selective IgG immunodeficiency, selective IgA immunodeficiency, X-linked agammaglobulinemia
  2. Polyclonal hyperimmunoglobulinemia
    • the blood level of all immunoglobulins is increased
    • sometimes, a particular immunoglobulin is increased more compared to others
    • autoimmune diseases → particularly IgG
    • primary biliary cirrhosis → particularly IgM
    • acute hepatitis → particularly IgG
  3. Monoclonal immunoglobulinemia
    • involves only one specific type of immunoglobulin
    • increased concentration due to the increased size of aparticular clone of plasma cells      → shown as a sharp peak on serum protein electrophoresis
    • eg., multiple myeloma      → plasma cell cancer      → IgG (most common), followed by IgA & IgD; IgM (rare)      → malignant plasma cells secrete M proteins