LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 1898
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size
IJPM is coming out with a Special issue on "Genitourinary & Gynecological pathology including Breast". Please submit your articles for these issues


 
  Table of Contents    
LETTER TO EDITOR  
Year : 2016  |  Volume : 59  |  Issue : 1  |  Page : 134-136
Immunoglobulin A gammopathy on serum electrophoresis: A diagnostic conundrum


Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Click here for correspondence address and email

Date of Web Publication9-Mar-2016
 

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;59:134-6

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 2019 Jul 17];59:134-6. Available from: http://www.ijpmonline.org/text.asp?2016/59/1/134/178245


Editor,

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: I - (a) Serum protein electrophoresis: Prominent M band in gamma region and a faint discrete band in beta region; (b) densitometer tracing: One sharp peak in gamma region; and (c) immunofixation electrophoresis: One band in immunoglobulin A heavy chain lane corresponding to "faint" band in beta region and one band in kappa light chain lane corresponding to the "prominent" M band in gamma region. II - (a) Serum protein electrophoresis: Prominent broad M band in beta - gamma region; (b) densitometer tracing: Broad peak in beta - gamma region; and (c) immunofixation electrophoresis: One band in immunoglobulin A heavy chain lane and one band in lambda light chain lane both corresponding to M band in beta - gamma region

Click here to view


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: I - (a) Serum protein electrophoresis: Two bands in gamma region; (b) Densitometer tracing: Two sharp peaks in gamma region; (c) immunofixation electrophoresis: Two bands each in immunoglobulin A heavy chain and kappa light chain lanes. II - (a) Serum protein electrophoresis: A prominent broad M band in beta - gamma region; (b) densitometer tracing: Broad peak in beta - gamma region; (c) immunofixation electrophoresis: One band in immunoglobulin A heavy chain lane corresponding to M band in beta - gamma region and two bands in lambda light chain lane higher one corresponding to M band and other band of excess free light chains. III - (a) Serum protein electrophoresis: Prominent band in beta - gamma region; (b) densitometer tracing: One peak in beta - gamma region, (c) immunofixation electrophoresis: No sharp band in any of lanes

Click here to view


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.

Acknowledgment

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

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Keren D. Protein Electrophoresis in Clinical Diagnosis. Great Britain: Hodder Arnold; 2003.  Back to cited text no. 1
    
2.
Keren D, editor. High-Resolution Electrophoresis and Immunofixation: Techniques and Interpretation. 2 nd ed. Stoneham, MA: Butterworth Publishers; 1994.  Back to cited text no. 2
    
3.
Tseng 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.  Back to cited text no. 3
    
4.
Sun T, Peng S, Narurkar L. Modified immunoselection technique for definitive diagnosis of heavy-chain disease. Clin Chem 1994;40:664.  Back to cited text no. 4
    
5.
Snyder 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.  Back to cited text no. 5
    

Top
Correspondence Address:
Seema Chhabra
Department of Immunopathology, Level 4 Research Block A, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.178245

Rights and Permissions


    Figures

  [Figure 1], [Figure 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
    Email Alert *
    Add to My List *
* Registration required (free)  


    References
    Article Figures

 Article Access Statistics
    Viewed2201    
    Printed25    
    Emailed0    
    PDF Downloaded75    
    Comments [Add]    

Recommend this journal