What are the causes of low globulins, specifically hypogammaglobulinemia (low gamma globulins)?

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Last updated: May 15, 2025View editorial policy

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From the Guidelines

Low globulins (hypoglobulinemia) can result from several underlying conditions, including primary causes like genetic disorders and secondary causes such as protein-losing conditions, malnutrition, and certain medications. The most recent and highest quality study 1 suggests that hypogammaglobulinemia can be caused by various factors, including genetic disorders, protein-losing conditions, and certain medications. Some key points to consider include:

  • Primary causes: genetic disorders like X-linked agammaglobulinemia, common variable immunodeficiency, and severe combined immunodeficiency
  • Secondary causes: protein-losing conditions such as nephrotic syndrome, protein-losing enteropathy, severe burns, or liver disease
  • Malnutrition and protein malabsorption can also lead to decreased globulin levels
  • Certain medications like immunosuppressants, chemotherapy drugs, and long-term corticosteroid use may suppress globulin production
  • Blood cancers like leukemia and lymphoma can affect the bone marrow's ability to produce normal blood components including globulins Treatment depends on identifying and addressing the underlying cause, which may involve immunoglobulin replacement therapy for primary immunodeficiencies, treating protein-losing conditions, improving nutritional status, or adjusting medications. The use of immunoglobulin replacement therapy is recommended for patients with hypogammaglobulinemia and recurrent severe infections, as well as for those with impaired vaccine responses 1. It is essential to consider the patient's individual needs and collaborate with an allergist/immunologist to determine the best course of treatment. Low globulin levels are concerning because they can compromise immune function, making patients more susceptible to infections, particularly recurrent bacterial infections. Therefore, it is crucial to monitor serum immunoglobulin levels and use intravenous immunoglobulin replacement or subcutaneous immunoglobulin therapy as needed to reach a target trough of 600-800 mg/dL and improve clinical outcomes 1.

From the Research

Causes of Low Globulins

  • Low globulins can be caused by various factors, including liver disease and kidney disease.
  • According to 2, angiotensin-converting enzyme inhibitors (ACEIs) can prevent liver-related events in nonalcoholic fatty liver disease, which may be related to globulin levels.
  • Kidney disease, such as that caused by multiple myeloma, can also lead to low globulins.
  • As stated in 3 and 4, multiple myeloma can cause kidney injury through various mechanisms, including the overproduction of monoclonal proteins, which can lead to low globulin levels.
  • Additionally, 5 discusses the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) in patients with acute kidney injury, which may be related to globulin levels.
  • However, it is essential to note that the provided studies do not directly address the causes of low globulins, but rather discuss related topics such as liver and kidney disease.
  • Further research is needed to fully understand the causes of low globulins, as the current evidence does not provide a clear answer to this question.

References

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.

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