Indications for SPE:
- Myeloma search: 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).
- Liver disease: It may also helpful
in liver disease detection & evaluation, mostly in cases of hyperproteinemia (especially if there is beta-gamma bridging) with hypoalbuminemia, for example.
- Neurology: work-up of peripheral neuropathy of undetermined etiology.
- Anemia: anemia of uncertain etiology in a renal insufficiency and/or bone-pain patient.
- Weakness and/or fatigue workup.
- Immunoglobulin deficiency cases.
- Recurrent infections cases.
- Abnormal lab values :
CBC smear review: rouleaux formation noted on CBC peripheral smear.
Nephrology: unexplained renal insufficiency, especially if with elevated serum protein.
ER & Orthopedic: unexplained bone pain or pathologic fracture or lytic bone lesion on X-ray.
- hypercalcemia of uncertain etiology
- elevated ESR of uncertain etiology
- hypergammaglobulinemia of uncertain etiology (reversed A/G ratio)
- heavy proteinuria in patient >40 y/o & look for 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
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
Hypogammaglobulinemia will indicate primary (see
Michigan Immunodeficiency Foundation list of
primary disorders) or secondary immunodeficiency disorders.
Since the clinical lab usually has no idea when/whether a monoclonal spike (M protein) has known significance, a lab-based terminology for small spikes has often been "mini-monoclonal" gammopathy. Though the term MGUS (monoclonal gammopathy of uncertain significance) is usually applicable to any new monoclonal gammopathy of as-yet-undetermined etiology, it sort of tends to be synonymous with "mini-monoclonal". It is these small ones that often elude specific identification of an etiology. Some can be so small that it is not absolutely certain that it is even a "minute" mini-monoclonal
- TWO BANDS = bisalbuminemia, an insignifcant hereditary situation.
OR THERAPEUTIC OVERDOSE of
- LIVER DISEASES (implies
reduced hepatocyte capacity)
- STARVATION OR MALNUTRITION
- CONGENITAL ANALBUMINEMIA
RENAL: NEPHROTIC SYNDROME
GUT: PROTEIN-LOSING GASTROENTEROPATHY
SKIN: SEVERE ECZEMA/MARKED
VESICULAR OR BULLOUS; BURN WOUNDS
ACUTE PHASE REACTIONS
ILLNESS & RECOVERY
FAMILIAL INCREASED CATABOLISM
CONSTITUENTS: alpha-1 antitrypsin.
- abnormal alpha-1 AT type (MGUSs rarely if ever migrate as far as the alpha-1 zone)
CONSTITUENTS: haptoglobin, alpha-2 macroglobulin, HDL.
BETA-GAMMA ZONE: With the various techniques & vendors to study serum proteins by SPE, a system is sufficiently sensitive when it (1) can crisply separate the beta region into its two subdivisions, transferrin & C3
and can (2) adequately portray a monoclonal or minimonoclonal peak or band down to the quantitative level of 0.1 gm/dl.
CONSTITUENTS: normally visualize transferrin and C3.
(OF CHRONIC IDA, PREGNANCY, BIRTH CONTROL PILLS)
- High LDL.
- Elevated C3
TRUE M-PROTEIN: IgA
- increases in IgA or IgM2.
PSEUDO-M: post-beta peak= excess antigen-specific IgA; IgG4 disease peak; IgM peak; excess IgM; elevated fibrinogen or CRP.
"Beta-gamma bridging" IS
MOST IMPORTANTLY TENDS TO BE ASSOCIATED WITH CHRONIC LIVER DISEASE and is a technical, visual phenomenon...as visble & best discerned on the electrophoretic membrane (tracing gives a "heads up" but is too sensitive)...denoting the reduction
of the depth of the valley (tracing) or distinctness of the 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 (we have rarely seen the
bridge when the SPE pattern & quantities are all otherwise normal). The zone "blurrs" or
"bridges" due to an increase in the polyclonal, anodally migrating portion of the total polyclonal IgG plus increased IgA & IgM which migrate
beta & gamma; it is sometimes alternatively called "beta-gamma fusion" or "beta gamma linking"2. This polyclonal
increase may be also
be due to a variety of other clinical situations: chronic infections, autoimmune or collagen disorders, metastatic carcinoma, cystic fibrosis and some
stages of thermal burns. We had a case in Oct. 2009 with bridging but negativity for hypoalbuminemia that was Hashimoto's thyroiditis. So, maybe bridging is related to oprgan-based diseases with lots of plasma cells. In truth, it is
a nonspecific finding that must be looked at in conjunction with the clinical situation and possibly followed by specific Ig testing and disease-specific profiles.
- "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, though some say this pattern has no definite diagnostic
- ABSENT beta-gamma zone: normal.
fibrinogen spike in someone
minimonoclonal: small M-spike within
a polyclonal zone ["MGUS"] determined to be monoclonal by immunofixation. If it goes away on subsequent testing a few weeks or so later, it might be referrd to as an "evanescent MGUS"
. The sensitivity for MGUS diagnosis is 0.1gm/dl7, 8. MGUS cases risk progression is at a rate of 1% per year7, 8. Annual status monitoring is standard in absence of "CRAB" (hyperCalcemia, Renal disease, Anemia, or Bone lesions)7, 8.
- Oligoclonal gammopathy: there can be (1) two or more small, ill-defined bands in a polyclonal background6 or (2) a significant increase in a narrow, tightly peaked, spike-like polyclonal zone
(a compact gamma-globulin band) as revealed by increases of both kappa & lambda. (1) is referred to as an oligoclonal gammopathy reflecting chronic immune stimulation or suppression; and (2) by that same term, said to be seen
more commonly in lupoid & auto-immune hepatitis & diseases with high levels of circulating immune complexes such as rheumatoid
arthritis with high RF levels)2, it being a nonspecific reflection of active autoimmunity4
. IgG-4 related disease may affect enough tissue volume to increase gama with9 or without a tight spike. But, modern electrophoretic plates sometimes detect seeming bands due to
broad increases might indicate
autoimmune disease vs. active chronic inflammation of non-autoimmune type.
- "Stair-step" immunofixation electrophoresis (IFE) pattern: in gamma is an "oligoclonal" pattern
in which there are (1) multiple tiny bands due to restricted IgG increases of chronic immune stimulation or (2) multiple tiny bands left behind as a reflection of chronic immunosuppression.
ASSOCIATED WITH RENAL INSUFFICIENCY OR MONOCYTIC LEUKEMIA
- American Family Physician SPE file.
- Ritzmann SE & Daniels JC, Serum Protein Abnormalities, Diagnostic and Clinical Aspects, about 1982, Alan R. Liss, Inc., New York. [JBC's office]
- Wikipedia HERE.
- Carter JB, personal communication.
- British Columbia Society for Laboratory Science web file on SPE with many membrane examples
- Mike Moss's LifeLabs web file HERE.
- Dr. John Carter, Memo about detection of small MGUS, 14 Feb. 2013 Based on Dr. Keren's book, below).
- David F. Keren, on-line SPE on PDF, his 2003 textbook HERE.
- Joannes F. M. Jacobs, MD, PhD, Renate G. van der Molen, PhD and David F. Keren, MD, PhD, "Relatively Restricted Migration of Polyclonal IgG4 May Mimic a Monoclonal Gammopathy in IgG4-Related Disease", AJCP 142(1):76-81, July 2014, HERE.
|(posted about 2001; latest addition 7 November 2017)