# Optimizing the Use of Serum Immunofixation for the Detection of Monoclonal Components in Hypogammaglobulinemia: Insights From a Tertiary-Care Biochemistry Laboratory

## TL;DR

This study shows that serum immunofixation electrophoresis (IFE) can detect monoclonal proteins missed by standard tests in patients with low antibody levels, improving diagnosis of immune-related disorders.

## Contribution

The study demonstrates that systematic serum IFE improves detection of monoclonal components in hypogammaglobulinemia, which may be masked by standard SPEP.

## Key findings

- Serum IFE identified monoclonal or oligoclonal abnormalities in 24.1% of hypogammaglobulinemic patients.
- Monoclonal gammopathies were predominantly IgG (67.8%) and IgA (30.5%) isotypes.
- Biclonal and light-chain-only patterns were detected, suggesting plasma-cell or B-cell disorders.

## Abstract

Hypogammaglobulinemia is a heterogeneous immunologic abnormality that may result from primary antibody deficiencies, secondary causes, or hematologic malignancies. Although serum protein electrophoresis (SPEP) is routinely used for initial evaluation, reduced γ-globulin levels may mask small monoclonal components, limiting the sensitivity of SPEP alone. Serum immunofixation electrophoresis (IFE), with its superior analytical resolution, may therefore be useful in the diagnostic assessment of hypogammaglobulinemia. The primary objective is to determine the diagnostic yield of systematic serum IFE in adult patients with hypogammaglobulinemia detected by SPEP, defined here as the proportion of patients in whom IFE identified a monoclonal or oligoclonal immunoglobulin abnormality not apparent on SPEP alone. The secondary objectives are to describe the immunochemical patterns identified (monoclonal vs. oligoclonal) and to characterise the detected isotypes (heavy-chain class and light-chain type), including biclonal and light-chain-only profiles. A retrospective descriptive study was conducted over a 12-month period (March 2023-March 2024) at the Central Biochemistry Laboratory of Mohammed VI University Hospital, Oujda, Morocco. Adult patients (≥16 years) presenting with hypogammaglobulinemia, defined as γ-globulin <8 g/L on SPEP, were included. Serum IFE was systematically performed to confirm or exclude the presence of monoclonal immunoglobulin components. Demographic and laboratory data were extracted from the laboratory information system and analyzed descriptively. A total of 261 patients were included (52.9% male; mean age 55.3 years, range 16-82). Most were referred from hematology (61.3%), internal medicine (23.0%), and oncology (15.7%). Serum IFE revealed monoclonal or oligoclonal abnormalities in 63 patients (24.1%), while 198 (75.9%) showed no detectable monoclonal component. Among the 63 abnormal profiles, 59 (93.6%) were monoclonal gammopathies, predominantly of IgG (67.8%) and IgA (30.5%) isotypes. Biclonal gammopathies accounted for 3.1% of cases, and another 3.1% exhibited isolated λ light-chain bands without detectable heavy chains, warranting further urinary immunofixation testing. These findings indicate that nearly one in four patients with hypogammaglobulinemia had a monoclonal component not identifiable by SPEP alone. Systematic serum IFE can therefore improve laboratory assessment by uncovering masked monoclonal components that SPEP may fail to detect. The predominance of IgG and IgA clones, together with the detection of biclonal and light-chain-only patterns, highlights the value of IFE in raising suspicion for clinically relevant plasma-cell and B-cell disorders. Accordingly, these results support considering routine IFE in selected hypogammaglobulinemic patients, particularly when clinical or laboratory features suggest an underlying monoclonal process.