What can cause abnormal serum protein electrophoresis (SPEP)?

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Last updated: April 8, 2025 • View editorial policy

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From the Guidelines

Abnormal serum protein electrophoresis (SPEP) results can be caused by various conditions, with the most concerning being multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), amyloidosis, and other plasma cell disorders that produce abnormal immunoglobulins, as reported in the most recent study 1.

Causes of Abnormal SPEP

The causes of abnormal SPEP results include:

  • Multiple myeloma
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Amyloidosis
  • Other plasma cell disorders
  • Chronic infections
  • Inflammatory conditions like rheumatoid arthritis or lupus
  • Liver diseases such as cirrhosis or hepatitis
  • Kidney diseases including nephrotic syndrome
  • Certain cancers like lymphoma

Diagnostic Approach

When an abnormal SPEP is found, further testing is typically needed, including:

  • Immunofixation electrophoresis
  • Free light chain assay
  • Complete blood count
  • Comprehensive metabolic panel
  • Possibly bone marrow biopsy depending on the specific abnormality The pattern of protein abnormalities helps determine the underlying cause, with different conditions showing characteristic changes in specific protein fractions, as noted in 2, 3, 4, 5, 6, 7.

Key Considerations

It is essential to use the same test for serial studies to ensure accurate relative quantification, as stated in 2. Additionally, the serum free light chain (FLC) assay is useful in monitoring disease response and progression in patients with non-secretory myeloma, as mentioned in 2.

From the Research

Causes of Abnormal Serum Protein Electrophoresis (SPEP)

Abnormal SPEP results can be caused by various conditions, including:

  • Monoclonal gammopathies, which are associated with a clonal process that is malignant or potentially malignant, such as multiple myeloma, Waldenström's macroglobulinemia, and solitary plasmacytoma 8
  • Polyclonal gammopathies, which may be caused by any reactive or inflammatory process 8
  • Acute inflammation, malignancy, trauma, necrosis, infarction, burns, and chemical injury, which can cause changes in plasma protein levels 8
  • Autologous stem cell transplantation (ASCT), which can lead to the development of oligoclonal patterns in SPEP results 9
  • Lymphoplasmacytic lymphoma, such as Waldenström's macroglobulinemia, which is characterized by the presence of IgM monoclonal protein 10

Specific Conditions Associated with Abnormal SPEP

Some specific conditions that can cause abnormal SPEP results include:

  • Multiple myeloma, which is characterized by a homogeneous spike-like peak in a focal region of the gamma-globulin zone 8
  • Waldenström's macroglobulinemia, which is characterized by the presence of IgM monoclonal protein and clonal lymphoplasmacytic cells in bone marrow 10
  • Plasma cell myeloma, which can lead to the development of oligoclonal patterns in SPEP results after ASCT 9
  • Chronic lymphocytic leukemia, which can have similar gene expression patterns to Waldenström's macroglobulinemia 11

References

Guideline

multiple myeloma, version 2.2016: clinical practice guidelines in oncology.

Journal of the National Comprehensive Cancer Network : JNCCN, 2015

Guideline

nccn clinical practice guidelines in oncology: multiple myeloma.

Journal of the National Comprehensive Cancer Network : JNCCN, 2009

Guideline

multiple myeloma.

Journal of the National Comprehensive Cancer Network : JNCCN, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.