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The Significance of Subtle Alterations in Routine Serum Protein Electrophoresis Patterns in One Laboratory

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The Significance of Subtle Alterations in Routine Serum Protein Electrophoresis Patterns in One Laboratory ̇your lab focus̈ interpretation [chemistry] The Significance of Subtle Alterations in Routine Serum Protein Electrophoresis Patterns in One Laboratory Stephen L. Strobel, MD From the Department of Pathology, St. Vincent Mercy Medical Center, Toledo, OH Downloaded from https://academic.oup.com/labmed/article/32/6/307/2657171 by guest on 30 September 2021 Visual inspection of the serum protein ferrin and C3 suggesting monoclonal electrophoresis pattern for the following gammopathy of undetermined signif- findings: icance (4 cases [0.6%]), and selective IgA ̈ Alpha1-antitrypsin deficiency deficiency (2 cases [0.3%]). Isolated sub- ̈ Prominent beta-lipoprotein band tle alterations observed in this patient pop- ̈ Minor monoclonal protein in the beta ulation, such as alloalbuminemia, were region not included in this study. ̈ IgA deficiency The Paragon SPE-II Electrophore- sis System (Beckman Instruments M) was used for all SPE specimens. The Serum protein electrophoresis (SPE) SPE-II system was used because of its is a laboratory method generally used superior resolution compared with con- for the evaluation of lymphoproliferative ventional agarose gel methodology, par- neoplasia, in particular multiple myel- ticularly for defining subtle alterations oma.1-3 However, additional disease con- in the gamma region. Serum samples ditions may be reflected in the SPE were evaluated at standard dilutions pattern, often in the form of subtle alter- according to the manufacturer’s guide- ations. Consistent identification of these lines. The Beckman Appraise Densito- subtle changes expands the clinical value meter (Beckman Instruments M) was and utility of the SPE. Visual inspection used to quantitate protein fractions. The of the SPE gel is mandatory for the de- Paragon Immunofixation Electrophore- tection of these subtle aberrations. Den- sis (IFE) kit (Beckman Instruments M) sitometric scans are inherently was used when corresponding IFE was inaccurate for the evaluation of these necessary. All patterns were evaluated slight changes and should be used only by a clinical pathologist. as an adjunct for follow-up of patients with known monoclonal gammopathies Alpha1-Antitrypsin Deficiency and objective assessment of the albumin For patients with alpha1-antitrypsin and gammaglobulin regions. deficiency, a band was visually In our evaluation of 723 SPE patterns detectable in the alpha1 region (albeit (340 men; 383 women; age range, 23 to fainter than the control and normal pa- 91 years; mean, 64 years; median, 62 tient samples of the corresponding gel). years) at St Vincent Mercy Medical Cen- Densitometric quantitation of the alpha1 ter, Toledo, OH, from July 1, 2000 zone in these patients was in the normal [I1] Subtle alterations in isolated protein through December 31, 2000, we observed range. Nephelometric quantitation of fractions of potential clinical significance 307 identified in serum protein electrophoresis 4 subtle alterations that occurred in multi- alpha1-antitrypsin confirmed a patterns (specific abnormalities designated by I1 ple different patient samples [ ]: alpha1- detectable but decreased level for each arrows): 1, Normal control pattern; 2, Alpha1- antitrypsin deficiency (3 cases [0.4%]), of these patients, suggesting heterozy- antitrypsin deficiency (heterozygous); 3, prominent beta-lipoprotein band suggest- gous phenotypic deficiency. Because Increased beta-lipoprotein fraction (comigrating with alpha -globulins); 4, Minor monoclonal ing hyperlipidemic state (5 cases [0.7%]), this deficiency may be associated with an 2 protein migrating between transferrin and C3, small monoclonal paraprotein in the beta increased risk or incidence of bronchitis, causing apparent fusion of these bands; 5, region comigrating with or between trans- pneumonia, and respiratory inflamma- Selective IgA deficiency. © laboratorymedicine> june 2001> number 6> volume 32 ̇your lab focus̈ 4 5 tion, Pi testing was recommended for this pattern (IgG kappa, 2; IgA kappa, 1. Keren DF. Procedures for the evaluation of each of these patients to confirm the 1; IgA lambda, 1). Long-term follow-up monoclonal immunoglobulins. Arch Pathol Lab diagnosis. Genetic counseling may also studies indicate that these small para- Med. 1999;123:126-132. be suggested in selected cases in which proteins may serve as early markers for 2. Kyle RA. Sequence of testing for monoclonal both members of a potential childbear- subsequent clinically significant lym- gammopathies. Arch Pathol Lab Med. 1999;123:114-118. ing couple demonstrate this enzyme phoproliferative disorders/plasma cell 9 3. George ED, Sadovosky R. Multiple myeloma: deficiency. dyscrasias. recognition and management. Am Fam Physician. 1999;59:1885-1894. Prominent beta-Lipoprotein IgA Deficiency 4. Luft FC. Alpha-1-antitrypsin and its relevance to Band Isolated IgA deficiency is observed human disease. J Mol Med. 1999;77:359-360. A very prominent beta-lipoprotein as a broad zone of decreased staining in- 5. Aslanidis C, Nauck M, Schmitz G. High-speed Downloaded from https://academic.oup.com/labmed/article/32/6/307/2657171 by guest on 30 September 2021 band is usually easily detectable by vi- tensity in the anodal portion of the detection of the two common alpha(1)–antitrypsin deficiency alleles Pi*Z and Pi*S by real-time sual inspection of the electrophoretic gamma region of the SPE. IgA deficiency fluorescence PCR and melting curves. Clin Chem. gel. However, the electrophoretic mo- may occur congenitally, with chronic 1999;45:1872-1875. bility of this protein is highly variable sinopulmonary disease, and ataxia telang- 6. Christie MB. Low-density lipoproteins and risk for coronary artery disease. Am J Cardiol. in the beta-alpha2 region, and comigra- iectasia. Patients with congenital 1998;82:3Q-12Q. tion with transferrin or alpha2-globulins deficiency of IgA are prone to autoim- is common. This can result in the un- mune diseases and may develop antibod- 7. Cullen P, Assmann G. Treatment goals for low- density lipoprotein cholesterol in the secondary derestimation of the band’s intensity, ies to IgA with associated increased risk prevention of coronary heart disease: absolute particularly if the densitometric scan is of anaphylaxis if they undergo blood levels or extent of lowering? Am J Cardiol. reviewed in isolation. Therefore, care product transfusion.10 Understaining of 1997;80:1287-1294. should be taken to correctly identify SPE samples impairs the ability to detect 8. Strobel SL. The incidence and significance of this band in each SPE pattern. When an this change, mandating technical consis- pseudoparaproteins in a community hospital. Ann Clin Lab Sci. 2000;30:289-294. increase of beta-lipoprotein is tency. The diagnosis of IgA deficiency 9. Colls BM. Monoclonal gammopathy of suspected, a fasting lipid profile may be cannot be based on the SPE pattern alone. undetermined significance: 31 year followup of a recommended as a screen for atheros- Quantitative analysis, such as nephelo- community study. Aust NZ J Med. 1999;29:500- clerotic vascular disease risk.6,7 metric measurement, is required. 504. 10. Rogers RL, Javed TA, Ross RE, et al. Transfusion Minor Monoclonal Protein in Conclusion management of an IgA deficient patient with anti- IgA and incidental correction of IgA deficiency the beta Region Alpha1-antitrypsin deficiency, ele- after allogeneic bone marrow transplantation. Am Minor monoclonal paraproteins vated beta-lipoprotein levels, minor J Hematol. 1998;57:326-330. (small monoclonal gammopathies of monoclonal paraprotein comigrating undetermined significance) may comi- with transferrin and C3, and selective InterNetConnect grate with transferrin and C38 or cause IgA deficiency were the 4 most com- fusion of the transferrin and C3 bands. mon subtle alterations identified in SPE For information on risk factors for cardiac Densitometric quantitation of the beta patterns in the patient population of our disease:<heartdisease.miningco.com/health/ region often yields normal results when laboratory over a 6-month period. heartdisease/cs/riskfactors/> the paraprotein concentration is mini- These changes were observed in iso- mal (<0.5 g/dL) or when there is a cor- lated protein fractions evident only by For information on selective IgA deficiency: <www.jmfworld.com/> responding decrease of the transferrin close visual inspection of the SPE gel. and/or C3 level. Visual inspection of Densitometric scans were insufficient Alpha 1 Association for Alpha-1-Antitrypsin the electrophoretic gel is therefore nec- for their identification. Detection of Deficiency: <www.alpha1.org/> essary to detect this alteration. these abnormalities is important Immunofixation electrophoresis con- because of their potential clinical sig- American Cancer Society Multiple Myeloma Resource Center: firms and identifies the paraprotein. In nificance. The incidence of these alter- <www3.cancer.org/cancerinfo/load_cont.asp this study, monoclonal paraproteins ations may vary for different ?ct=30> were demonstrated in 4 samples with laboratories and regions. 308 laboratorymedicine> june 2001> number 6> volume 32 ©.
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