What are the causes of low serum globulins (hypogammaglobulinemia)?

From the Guidelines

Low serum globulins, or hypogammaglobulinemia, is often caused by immune deficiencies, such as those seen in patients with multiple myeloma receiving bispecific antibody therapy, which can lead to prolonged hypogammaglobulinemia and increased infection risk 1. This condition requires medical evaluation to determine the underlying cause, which may include protein-losing conditions, malnutrition, or liver disease. Some key points to consider in the evaluation and management of hypogammaglobulinemia include:

• Immune deficiencies, such as those associated with multiple myeloma, can lead to hypogammaglobulinemia and increased infection risk 1
• Patients with hypogammaglobulinemia and recurrent severe infections may benefit from immunoglobulin supplementation, as recommended by the American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis 1
• The decision to initiate immunoglobulin replacement therapy should be made in collaboration with an allergist/immunologist and based on the specific underlying cause of the hypogammaglobulinemia, as outlined in the Journal of Allergy and Clinical Immunology 1
• Patients with low globulins should seek medical attention for proper diagnosis through blood tests, including protein electrophoresis, immunoglobulin levels, and liver function tests. While awaiting diagnosis, patients should practice good hygiene and avoid exposure to infections due to potentially compromised immunity. Supplemental nutrition may help if malnutrition is contributing, but this should be guided by a healthcare provider. Globulins are critical for immune function, with immunoglobulins (antibodies) being the most important type for fighting infections. Other globulins transport hormones, metals, and lipids throughout the body. Treatment success depends on addressing the specific cause rather than simply supplementing globulins directly.

From the Research

Causes of Low Serum Globulins (Hypogammaglobulinemia)

• Primary immune deficiency, such as common variable immune deficiency (CVID) 2, 3, 4, 5
• Secondary immune deficiency, including:
  • Hematological malignancy 2
  • Iatrogenic immune deficiency due to immunosuppressants or antiepileptic drugs 2
  • Renal or gastrointestinal immunoglobulin losses 3
• Multiple myeloma (MM), including light chain and non-secretory MM 2, 4
• Decreased maternal transfer or production in neonates, including physiological nadir, transient hypogammaglobulinemia of infancy, medication effects, or immunodeficiency 6
• Increased loss of immunoglobulins, such as:
  • Gastrointestinal (GI) system loss 6
  • Lymphatic loss 6
  • Kidney loss 6
  • Skin disease 6
  • Blood loss 6
• Destruction or suppression of immunoglobulins, including medication effects 6