Indian Journal of Pathology and Microbiology

: 2016  |  Volume : 59  |  Issue : 1  |  Page : 134--136

Immunoglobulin A gammopathy on serum electrophoresis: A diagnostic conundrum

Frainey Bansal, Priyanka Bhagat, Vishrut K Srinivasan, Seema Chhabra, Parikshaa Gupta 
 Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Seema Chhabra
Department of Immunopathology, Level 4 Research Block A, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012

How to cite this article:
Bansal F, Bhagat P, Srinivasan VK, Chhabra S, Gupta P. Immunoglobulin A gammopathy on serum electrophoresis: A diagnostic conundrum.Indian J Pathol Microbiol 2016;59:134-136

How to cite this URL:
Bansal F, Bhagat P, Srinivasan VK, Chhabra S, Gupta P. Immunoglobulin A gammopathy on serum electrophoresis: A diagnostic conundrum. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Sep 21 ];59:134-136
Available from:

Full Text


A 62-year-old female presented to oral health sciences department with a complaint of gradually progressive swelling in right lower jaw near the molar teeth region along with dyspepsia and body aches for 3 months. On examination, a clinical suspicion of giant cell tumor versus Brown's tumor was suggested. Serum parathyroid hormone levels were elevated (135 ng/ml; normal 15-65 ng/ml). Sestamibi parathyroid scintigraphy did not reveal any parathyroid lesion. Orthopantomogram revealed multiple lytic lesions in left ramus and right angle of the mandible. Fine needle aspiration from the swelling showed plasmacytoma. A tissue biopsy confirmed the diagnosis of plasmacytoma. Bone marrow examination showed 9% plasma cells, the majority being immature forms. Hemogram revealed mild anemia. Serum creatinine, electrolytes, total protein (TP), and albumin: globulin ratio were within the normal limits.

Serum protein electrophoresis (SPEP) showed a prominent M band in the gamma region and a faint discrete band in the beta region [Figure 1.Ia and 1.Ib. Immunofixation electrophoresis (IFE) showed single discrete band in immunoglobulin A (IgA) heavy chain lane [Figure 1].Ic corresponding with the level of "faint" band seen in TP electrophoresis and an intense band in kappa light chain lane which was placed at the level of "prominent" M band in TP electrophoresis with no corresponding band in any of the heavy chain lanes. Serum free light chain assay revealed greatly elevated kappa free light chains (>1650 mg/L; normal 3.30-19.40 mg/L).{Figure 1}

IgA monoclonal Ig produces a broad band near beta region [Figure 1].II] owing to higher molecular weight. [1] The broadband can be attributed to the fact that IgA monoclonal Ig molecules tend to self-aggregate resulting in the formation of multimers. The combination of fast moving monomeric IgA molecules and slow moving multimeric (dimers, trimers) molecules yields a broader band compared to IgG molecule. [2] IgA monoclonal Igs form complexes with other serum proteins contributing further for the broader nature of the band. [3] The difference in mobility of IgA monomers and dimers may produce 2 distinct bands on SPEP raising a suspicion of biclonal gammopathy, however this gets resolved on IFE [Figure 2].I] where 2 bands are seen in the IgA heavy chain lane along with 2 corresponding bands in same light chain lane [kappa in the [Figure 2].I].{Figure 2}

In certain instances, excess free light chains are produced which do not combine with heavy chains to produce complete monoclonal Ig molecules and produce separate distinct bands in light chain lane on IFE [Figure 2].II giving rise to 2 bands in light chain lane, one corresponding to complete monoclonal Ig molecule, and other due to excess free light chains which move faster.

In the index case, the band in IgA lane is not showing any corresponding band in any of 2 light chain lanes. Owing to its quaternary structure, the light chains' epitopes can get sequestered due to folding of IgA molecule. Hence, the corresponding light chain is not detected by respective antisera. This should be reported as "IgA with no apparent light chain attached." Repeat testing with β-mercaptoethanol (which depolymerizes IgA molecule) is advised to confirm this entity. Though rare, IgA heavy chain disease should be considered. Heavy chain disease cannot be determined from IFE. In such situation, further testing (immunoselection) is recommended. [4] In the present case, though the presence of the IgA band without a corresponding light chain band is explainable, the prominent band seen on TP electrophoresis with a corresponding prominent band in kappa light chain lane without a band in any of the heavy chain lanes remained unresolved. Such cases may pose diagnostic dilemmas and require repeat testing and follow-up.

The location of IgA band in SPEP is close enough to that of fibrinogen band which can lead to misinterpretation sometimes [Figure 2].III. It is seen in the case of inadequately clotted blood sample due to improper collection or presence of anticoagulant in specimen vial which prevents clotting. So, it is advisable to repeat the electrophoresis with a fresh sample or use pretreatment with ethanol to precipitate out fibrinogen. Fibrinogen does not show band in any of the heavy chain lanes and kappa light chain lane on IFE but may show sometimes a thin band in lambda light chain lane. [2] . To conclusively detect monoclonal gammopathy, it is advisable to run 3 lane IFE with anti-kappa, anti-lambda, and anti-fibrinogen antisera in such cases. [2] Snyder et al. observed fibrinogen band precipitating with IgA antiserum. [5]

The spectrum of IgA gammopathy on electrophoresis is diverse, and one should be aware of possible variations to avoid misdiagnosis.


We would like to thank Dr. Biman Sailkia and Dr. Ritu Aggrawal for sharing their valuable experience with us and for providing some electrophoresis photographs.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Keren D. Protein Electrophoresis in Clinical Diagnosis. Great Britain: Hodder Arnold; 2003.
2Keren D, editor. High-Resolution Electrophoresis and Immunofixation: Techniques and Interpretation. 2 nd ed. Stoneham, MA: Butterworth Publishers; 1994.
3Tseng CH, Chang CY, Liu KS, Liu FJ. Accuracy of serum IgM and IgA monoclonal protein measurements by densitometry. Ann Clin Lab Sci 2003;33:160-6.
4Sun T, Peng S, Narurkar L. Modified immunoselection technique for definitive diagnosis of heavy-chain disease. Clin Chem 1994;40:664.
5Snyder JA, Willis MS, Grenache DG. Immunofixation reveals an apparent alpha heavy chain caused by precipitation of fibrinogen with IgA antiserum. Clin Chim Acta 2006;368:192-4.