Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        Serum Protein Electrophoresis (SPE)
      

Indications for SPE:

  1. The most common reason for doing the SPE is to check for the presence of a monoclonal gammopathy (suspect multiple myeloma...bone lesions...back pain, Waldenstrom's, amyloidiosis).
  2. It may also helpful in liver disease detection & evaluation: in cases of hyperproteinemia (especially if there is beta-gamma bridging) with hypoalbuminemia, for example.
  3. work-up of peripheral neuropathy of undetermined etiology.
  4. anemia of uncertain etiology in a renal insufficiency and/or bone-pain patient.
  5. hypercalcemia of uncertain etiology.
  6. rouleaux formation noted on CBC peripheral smear.
  7. renal insufficiency with elevated serum protein.
  8. unexplained pathologic fracture or lytic bone lesion on X-ray.
  9. Bence Jones proteinuria.

Interpretation is enhanced by having knowledge of the serum total protein and albumin levels...then an A/G ratio can be checked (normal being 1.0 or slightly higher).

A sample of serum (with known albumin determination value) is placed on the moist electrophoretic  membrane to which an electric charge is applied. The charge causes various proteins to reliably migrate certain distances in certain amounts of time. The membrane is then stained and submitted for a densitometer tracing of the variable degrees of protein staining along the protein migration line. The clinical pathologist then has:

  •  the analytic value for serum albumin, 
  • the visible membrane pattern, and 
  • the densitometer tracing quantitation in order to make a screening-level diagnosis.
Should there be any suggestion of monoclonal gammopathy among the above three lines of evidence, then immunofixation electrophoresis (IFE...IFX) can be carried out on the same sample. We do this at no additional charge so that an abnormal protein workup can be expeditiously finalized.

Suspicion of monoclonal gammopathy...presence of "M-protein"...is most commonly noted on the membrane in the "gamma" region. But, "M-protein" can be present in the beta or beta-gamma zone, too (it may be problematic to discern in those locations). And, one occasionally notes pseudo-M-proteins. [serological methods]

Hypogammaglobulinemia will indicate primary (see Michigan Immunodeficiency Foundation list of primary disorders) or secondary immunodeficiency disorders.

ALBUMIN ZONE:

  • CONSTITUENTS:
  • ELEVATIONS: DEHYDRATION OR THERAPEUTIC OVERDOSE of albumin
  • DECREASES:
    • DECREASED SYNTHESIS:
      • LIVER DISEASES (implies reduced hepatocyte capacity)
      • STARVATION OR MALNUTRITION
      • CONGENITAL ANALBUMINEMIA
    • LOSS:
      • RENAL: NEPHROTIC SYNDROME
      • GUT: PROTEIN-LOSING GASTROENTEROPATHY
      • SKIN: SEVERE ECZEMA/MARKED VESICULAR OR BULLOUS; BURN WOUNDS
    • INCREASED CATABOLISM:
      • PSEUDO-M: BISALBUMINEMIA
      • ACUTE PHASE REACTIONS
      • PREGNANCY
      • ILLNESS & RECOVERY
      • THYROTOXICOSIS
      • WISKOTT-ALDRICH SYNDROME
      • FAMILIAL INCREASED CATABOLISM
ALPHA-1 ZONE:

  • CONSTITUENTS:
  • ELEVATIONS:
    • PSEUDO-M: HYPER-ALPHA-2
  • DECREASES:
ALPHA-2 ZONE:

  • CONSTITUENTS:
  • ELEVATIONS:
    • PSEUDO-M:
  • DECREASES:
BETA ZONE:

  • CONSTITUENTS:
  • ELEVATIONS:
    • PSEUDO-M: HYPERTRANSFERRINEMIA (OF  CHRONIC IDA, PREGNANCY, BIRTH CONTROL PILLS) 
    • TRUE M-PROTEIN: IgA
    • increases in IgA or IgM2.
  • DECREASES:
BETA-GAMMA ZONE:

  • PRESENCE/ELEVATIONS:
    • PSEUDO-M:
    • "Beta-gamma bridging " IS HIGHLY ASSOCIATED WITH CHRONIC LIVER DISEASE and is...as visble on the membrane or tracing...the reduction of the valley (tracing) or clear zone (membrane) between the beta peak and the gamma peak. Since the liver disease might be occult as to other liver function tests, decisions must be made about the sensitivity level of "calling" a beta-gamma bridge. The zone blurrs or bridges due to an increase in the anodally migrating part of IgG plus increased IgA & IgM which tend to be in the beta globulin fraction2. It is sometimes alternatively called beta-gamma fusion or beta gamma linking2.
    • ABSENT: normal.
    • "Stair-step" PATTERN: the alpha 1, alpha 2, and gamma zones on the tracing form peaks with blunting of the beta-gamma valley and the successive peaks visually remindful of upward stairsteps; think of sarcoidosis and/or chronic liver disease.
GAMMA ZONE:

  • CONSTITUENTS:
  • ELEVATIONS:
    • PSEUDO-M:
    • fibrinogen spike in someone on heparin
    • minimonoclonals within a polyclonal zone ["MGUS"]
    • there can be a significant increase in a narrow polyclonal zone (a compact gamma-globulin band) as revealed by increases of both kappa & lambda & referred to as an oligoclonal gammopathy (seen more commonly in auto-immune hepatitis & diseases with high levels of circulating immune complexes such as rheumatoid arthritis with high RF levels)2.
    • broad increases might indicate autoimmune disease
  • DECREASES:
POST-GAMMA ZONE:
  • PRESENCE/ELEVATIONS: HYPERLYSOZYMEMIA ASSOCIATED WITH RENAL INSUFFICIENCY OR MONOCYTIC LEUKEMIA

References:

  1. American Family Physician SPE file.
  2. Ritzmann SE & Daniels JC, Serum Protein Abnormalities, Diagnostic and Clinical Aspects, about 1982, Alan R. Liss, Inc., New York. [JBC's office]
(posted about 2001; latest addition 27 October 2009)
 
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