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Serum Protein Electrophoresis -Interpretation

Serum protein electrophoresis separates proteins based on their charge, size and shape. Albumin is the major component of serum protein and constitutes the first peak on left

In electrophoreis Gamma zone comprises mainly of Immunoglobulins which are made of two protein moeties called heavy and light chains Antibodies are made of gamma globulin called an Immunoglobulin Immunoglobulins are glycoprotein molecules – produced by plasma B cells in response to specific immunogens and function as antibodies Each B cell produces a unique antibody ( monoclonal antibody ) Five classes of Immunoglobulins – see table

Gammopathy is
 abnormal proliferation of lymphoid cells producing Immunoglobulins. 
Important to differentiate if monclonal or polyclonal

Test for Immunoglobulins via 
Serum Protein Electrophoresis ( SPEP ) Tests done normally to detect abnormality of 3 classes IgG , IgA and IgM Ig levels provide information of the humoral immune system Levels can be low ( deficiency ) , raised or a combination of increased and decreased levels Low level of Ig is called hypogammaglubulinaemia ( ↓ ed gamma GBlin)

Low levels- Low levels indicated some form of humoral immunodeficiency

Immunodeficiency can be isolated defect or a wider combined T and B cell deficiency-family h/o immunodeficiency recurrent severe or unusual bacterial infections lack of response to antibiotics chronic unexplained diarrhoea unusual recurrent viral infections

High –High level- polyclonal gammopathy can indicate – liver disease chronic inflammatory disease haemtological disorders infection

Monoclonal- see on right.Conditions with chronic inflammation as Rh arthritis , SLE , autoimmune liver disease or chronic infection as HepC, HIV Malignancy as myeloma . lymphoma, CLL

In normal serum about 75-80 % is IgG , 15 % IgA and 5 % IgM.

Protein electrophoresis separates the proteins in a blood or urine sample based on size and charge -in most patients with multiple myeloma large amounts of an abnormal Ig protein-M-spike on the graph which can be studied 
further with 

levels decreased-Called primary or inherited these are rare and unlikely to be 1st presentation in General Practice. Secondary or acquired –More common Causes include
○ nephrotic syndrome
○ protein loosing entropathies
 ○ immunospressive Rx
○ light chain or non-secretory myeloma

Selective isolated IgA deficiency is the most common immunodeficiency ( primary cause ) Patients with X -linked agammaglobulinaemia have low or undetectable levels of all Ig’s due to an abnormality in B cell development Common variable immune deficiency- most common severe antibody deficiency ( emergency ) hypogammaglobulinaemia , poor specific antibody responses to vaccinations and an ↑ed incidence of autoimmune disease particularly autoimmune cytopenias 

monoclonal gammopathy-IgM paraproteinaemia
○ Waldenstroms’s macroglobulinaemia
○ Other Non-Hodgkins lymphoma IgG or IgA paraproteinaemia
○ Myeloma 
smlouldering or symptomatic
○ Plasmacytoma
○ Amyloidosis
○ POEMS.Monoclonal gammopathies are 
associated with a clonal process that is malignant or potentially 
malignant.Once a monoclonal gammopathy is identified by electrophoresis – Multiple Myeloma must be differentiated from other causes of this type of gammopathy

Polyclonal gammopathy-Chronic and acute infections e.g HIV , EBV , CMV Conn tissue dis e.g Rh arthritis, SLE , ecleroderma Chronic active autoimmune hepatitis Primary biliary cirrhosis Neoplasm ( lung , liver , gastric )

Polyclonal gammopathy implies a non-specific immune response/ reaction and can be caused by any reactive or inflammatory process and usually not associated with an underlying malignant condition or a haematological disorder


  1. Quantitative serum immunoglobulin tests Richard KS Loh et al Australian Family Physician , Vol 42 , No4 , April 2013
  2. Elevated immunoglobulins and paraproteins by Dr Aristeidis Chaidos Consultant haematologist and honorary senior lecturer Hammersmith Hospital Imperial College Healhcare NHS Trust Power Point presentation
  3. Mayo Clinic Laboratories -Test ID Immunoglobulins
  4. Labpedia net via
  5. Understanding and Interpreting Serum Protein Electrophoresis Theodore X O’Connll et al Am Fam Physician .2005 Jan 1;71 (1) ;105-112
  6. Immunoglobulins structure and function Gene Mayer Ph.D via
  7. Immunoglobulins – Structure and Function via



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