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'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. in AAT deficiency, 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 in transferrin and β1. Familial hypercholesterolemia causes a β2 spike.

5/ Gamma portion: main utility of SPEP.
If , suspect humoral immune dysfunction w/ hypogammaglobulinemia.
If , suspect gammapathy and determine if monoclonal or polyclonal.

When to order a SPEP? (courtesy of AAFP, 2005)

6/ Case #1:

What pathology is this pattern most compatible with?

6/ What pathology is this pattern most compatible with?

7/ Answer: Inflammation

Note albumin (acute phase reactant) & α1/α2 (phase reactants).
Dehydration expected to cause 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 (albumin, Ig) with compensatory 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. albumin.
A:G ratio<1 (albumin, 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 ( if GFR ).

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.sciencedirect.com/topics/medicine-and-dentistry/protein-electrophoresis

Interprétation 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 cases:
http://ucsdlabmed.wikidot.com/chapter-7-laboratory-diagnosis-of-protein-abnormalities