Interpretation of Globulin 1.7 g/dL and A/G Ratio 3.0
These values indicate significant hypoglobulinemia (globulin 1.7 g/dL is well below the normal range of 1.8-3.7 g/dL) and warrant immediate investigation for primary or secondary antibody deficiency, as this degree of low globulin has been shown to detect clinically significant immunodeficiency in approximately 89% of cases. 1
Clinical Significance of These Values
A globulin level of 1.7 g/dL falls below the established screening threshold of <1.8 g/dL (18 g/L), which has 89% sensitivity for detecting IgG levels <6 g/L and 56% sensitivity for IgG <4 g/L. 1
The A/G ratio of 3.0 is markedly elevated (normal range approximately 0.8-2.0), which inversely correlates with the low globulin and further supports the presence of hypoglobulinemia. 2
In a study of 826 patients with calculated globulin <18 g/L, both primary antibody deficiencies (including common variable immunodeficiency) and secondary immunodeficiencies were detected, along with 1.2% having previously undetected paraproteins with immune-paresis. 1
Immediate Diagnostic Workup Required
Order the following tests immediately:
- Serum protein electrophoresis (SPEP) to evaluate for paraproteins or immune-paresis 1
- Quantitative immunoglobulin levels (IgG, IgA, IgM) to assess for antibody deficiency 3, 1
- Immunofixation if SPEP shows abnormalities, as 1.2-2.2% of patients with low globulin have light chain or non-secretory multiple myeloma 3, 1
Differential Diagnosis to Consider
Primary causes:
- Common variable immunodeficiency (CVID) - the most important primary antibody deficiency to exclude 3, 1
Secondary causes (account for ~67% of cases with low globulin):
- Hematological malignancies (47% of patients in one cohort) - including lymphoma, chronic lymphocytic leukemia, multiple myeloma with immune-paresis 3
- Iatrogenic immunosuppression (20% of patients) - from immunosuppressants, antiepileptic drugs, or other medications 3
- Protein-losing conditions - nephrotic syndrome, protein-losing enteropathy 1
- Severe malnutrition or malabsorption 1
Clinical Implications and Monitoring
Patients with antibody deficiency detected through low globulin screening have shortened diagnostic delay and earlier initiation of immunoglobulin replacement therapy when needed. 1
Approximately 23% of patients with low globulin have multiple comorbid conditions with unexplained hypogammaglobulinemia requiring ongoing clinical and laboratory surveillance. 3
If immunoglobulin levels are confirmed to be low, assess for recurrent sinopulmonary infections, bronchiectasis, or other infectious complications that would indicate need for immunoglobulin replacement therapy. 3, 1
Important Caveats
Ensure albumin was measured using bromocresol green methodology; if bromocresol purple was used, the calculated globulin cutoff should be adjusted to <23 g/L rather than <18 g/L. 1
A single low globulin value requires confirmation with repeat testing and quantitative immunoglobulin measurements before definitive diagnosis. 1
Even in "otherwise healthy" patients, low globulin can unmask previously unrecognized immunodeficiency or early hematological malignancy. 3