A Single Center Study Investigating Clinical Outcomes of Testing for Multiple Myeloma and Immune Deficiency at Low Globulin Levels

Abstract

Background

Both primary (e.g. common variable immune deficiency, CVID) and secondary immune deficiency as well as multiple myeloma (MM) require medical intervention and treatment delay can exacerbate morbidity. This study investigated the potential importance of low levels of calculated globulin to detect immune deficiency and MM associated with immunoparesis (light chain, non-secretory MM).

Methods

One hundred and thirty-nine patient serum samples from community physicians and outpatient clinics for liver function tests with low calculated globulin (<16 g/L, RR 18–37 g/L) levels were screened for immunoglobulins and protein electrophoresis. Further, 110 patients with globulin levels ≤16 g/L with screening for immunoglobulin levels and protein electrophoresis, requested through routine clinical care, were included in the analysis.

Results

Approximately 47% of patients in this cohort had secondary antibody deficiency as a result of hematological malignancy. Secondary iatrogenic (immunosuppressants, antiepileptic drugs) immune deficiency was detected in 20% of patients and a significant percentage of the patients were found by reflex testing at globulin levels <16 g/L. During the study period the screening detected new light chain and non-secretory MM in 2.2% of patients. Three patients with CVID and six patients with light chain myeloma were previously detected by screening, consequently alerting clinicians and reducing delay in treatment. A further 23% with several co-morbid conditions showed unexpected hypogammaglobulinemia; in this category, the study identified a subgroup that required further investigation.

Conclusion

Investigation of low globulin levels detects patients with primary and secondary immune deficiency and MM. Optimizing treatment for decreased immunoglobulins in patients with other clinical co-morbidities may require increased clinician awareness and watchful clinical and laboratory assessment.

Keywords:

• calculated globulin
• primary immune deficiency
• common variable immune deficiency
• secondary immune deficiency
• light chain myeloma
• non-secretory myeloma

Data Sharing Statement

The data are stored in the Laboratory Quality Management System of The Worcester Royal Hospital, and are available following anonymization of patient identifiable information. The full data set can be requested from the corresponding author upon approval of the paper proposal using the data.

Ethics Approval and Consent to Participate

The study was an audit carried out according to the Declaration of Helsinki and the NHS Data Protection Act. Approval for the study was granted by the Research and Ethics Committee of the Worcester Acute Hospitals NHS Trust as per NHS Data Protection Act. Informed verbal consent was obtained from patients and approved by the Research and Ethics Committee of the Worcester Acute Hospitals NHS Trust.

Consent for Publication

The study is a service audit (carried out as a cross-sectional observational study, according to STROBE guidelines). Informed verbal consent was obtained from patients and approved by the Research and Ethics Committee of the Worcester Acute Hospitals NHS Trust.

Author Contributions

I am the sole author of the manuscript and made a significant contribution to the work reported, in the conception, study design, execution, acquisition of data, analysis and interpretation; took part in drafting, revising and critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The author reports no competing interests in this work.