1/ There is more to serum protein electrophoresis (SPEP) than meets the eye. A SPEP is a rich exam, with a wealth of information, that has been relegated to the land of malignant hematology with advances in lab testing. Let& #39;s rediscover its richness through a few clinical cases.
2/ This is what a normal SPEP pattern looks like. Albumin (60%) - globulins (40%). Normal A:G ratio 1.5-2.5.
Globulins comprise alpha 1, alpha 2, beta 1, beta 2 and gamma globulin portions.
3/ Alpha 1 portion: contains alpha1-antitrypsin. Positive acute phase reactant. https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">in AAT deficiency, https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">in inflammation & pregnancy.

Alpha 2 portion: contains ceruloplasmin & haptoglobin. Positive acute phase reactant.
4/ Beta 1 portion: contains transferrin. Pre-β region contains VLDL.

Beta 2 portion: contains beta-lipoprotein (mainly LDL).

IgA and IgM are in beta portion of SPEP.

Iron deficiency anemia causes https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> in transferrin and β1. Familial hypercholesterolemia causes a β2 spike.
5/ Gamma portion: main utility of SPEP.
If https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">, suspect humoral immune dysfunction w/ hypogammaglobulinemia.
If https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">, suspect gammapathy and determine if monoclonal or polyclonal.

When to order a SPEP? (courtesy of AAFP, 2005)
5/ Gamma portion: main utility of SPEP. If https://abs.twimg.com/emoji/v2/... draggable=, suspect humoral immune dysfunction w/ hypogammaglobulinemia. If https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">, suspect gammapathy and determine if monoclonal or polyclonal.When to order a SPEP? (courtesy of AAFP, 2005)" title="5/ Gamma portion: main utility of SPEP. If https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">, suspect humoral immune dysfunction w/ hypogammaglobulinemia. If https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">, suspect gammapathy and determine if monoclonal or polyclonal.When to order a SPEP? (courtesy of AAFP, 2005)" class="img-responsive" style="max-width:100%;"/>
6/ Case #1:

What pathology is this pattern most compatible with?
6/ What pathology is this pattern most compatible with?
7/ Answer: Inflammation

Note https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow"> albumin (https://abs.twimg.com/emoji/v2/... draggable="false" alt="➖" title="Heavy minus sign" aria-label="Emoji: Heavy minus sign">acute phase reactant) & https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">α1/α2 (https://abs.twimg.com/emoji/v2/... draggable="false" alt="➕" title="Heavy plus sign" aria-label="Emoji: Heavy plus sign">phase reactants).
Dehydration expected to cause https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> albumin (hemoconcentration).
CVID expected to cause flattening of γ portion.
AAT def. causes flattening of α1 (SPEP now replaced w/ serum AAT level).
8/ What pathology is this pattern most compatible with?
8/ What pathology is this pattern most compatible with?
9/ Answer: Nephrotic syndrome.

Loss of small-size proteins in urine (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">albumin, Ig) with compensatory https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">liver production of large proteins leading to α2 spike (α2-Macroglobulin & VLDL).
IDA can cause a β1 spike.
10/ Case #3:

What pathology is this pattern most compatible with?
10/ What pathology is this pattern most compatible with?
11/ Answer: cirrhosis

Early cirrhosis: beta-gamma bridging (related to increase in IgA and transferrin production?). Fairly characteristic of cirrhosis.
Advanced cirrhosis: poor synthetic function. https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">albumin.
A:G ratio<1 (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">albumin, https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">Ig).
12/ Case #4:

What combination of pathologies is this pattern compatible with?
12/ What combination of pathologies is this pattern compatible with?
13/ Answer: SLE/cirrhosis

When faced with a gammapathy (large protein or gamma gap), identify if pattern is monoclonal or polyclonal.
13/ Answer: SLE/cirrhosis

Broad-based peak in this case is suggestive of polyclonal gammapathy, a condition seen in both SLE and cirrhosis.
14/ Case #5:

What condition is the most likely diagnosis in this case?
14/ What condition is the most likely diagnosis in this case?
15/ Answer: IgG multiple myeloma

There is evidence of monoclonal gammapathy (narrow-based peak). M-protein level seems elevated and predominant in the γ region, mostly compatible with smoldering or active IgG MM.
IgA MGUS should cause a smaller spike shifted more to the left.
16/ Always interpret SPEP in clinical context.
If a plasma cell disorder is still suspected despite a normal SPEP, order a serum free light chain assay (sFLC). Up to 20% of plasma dyscrasias only produce light chains lost in urine. A normal sFLC ratio is 0.26-1.65 (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> if GFR https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">).
Please share your thoughts/questions below.
Further reading:
Understanding and Interpreting Serum Protein Electrophoresis
https://www.aafp.org/afp/2005/0101/p105.html

https://www.aafp.org/afp/2005/... href=" https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-electrophoresis

Interprétation">https://www.sciencedirect.com/topics/me... de l’électrophorèse
des protéines sériques. (in French)
http://www.fmc-tourcoing.org/new/wp-content/uploads/2015/12/Electrophores-des-proteines-seriques-R.pdf

Interesting">https://www.fmc-tourcoing.org/new/wp-co... cases:
http://ucsdlabmed.wikidot.com/chapter-7-laboratory-diagnosis-of-protein-abnormalities">https://ucsdlabmed.wikidot.com/chapter-7...
Understanding and Interpreting the Serum Protein Electrophoresis

Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders. Electrophoresis separates proteins based on their physical properties, and the...

https://www.aafp.org/afp/2005/0101/p105.html
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