An unexpectedly high IgE level during allergic exploration

Summary

https://doi.org/10.1093/clinchem/hvae151

A 78-year-old man presented to the hospital with hemoptysis.

Student discussion

Guillaume Feugray, Jennifer Guillerme, Stéphanie Pramil, Marion Carrette, and Muriel Quillard Muraine

Case description

A 78-year-old man presented to the hospital with hemoptysis. The patient’s medical history included active smoking, dyslipidemia, diabetes, and hypertension. A thoracic scan revealed pulmonary emphysema associated with bronchial dilatation and diffuse bronchial thickening. Some calcified micronodules were observed, with a 5.2 mm posterobasal nodule in the right lobe. Based on these findings, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was suspected. Laboratory tests revealed an extremely high level of total immunoglobin E (IgE), with a titer of >5000 kU/L [reference value (RV) < 114 kU/L for an adult] and anti-Aspergillus fumigatus-specific IgE of 0.2 kU/L (RV < 0.1 kU/L) (Phadia250®, Thermo Fisher). Aspergillus serology was negative and the diagnosis of ABPA was excluded. Complete blood count was normal except for lymphopenia (1.12 × 10⁹/L) and thrombocytopenia (136 × 10⁹/L). Results were also normal for renal and hepatic blood parameters (Cobas®8000, Roche).

Systematic serum protein electrophoresis (SPE) (Capillarys2®, Sebia) found highly suspicious anomalies in the gamma-globulin fraction. Given this result, we performed serum immunofixation (IF) (Hydrasys®, Sebia) with 5 antisera [anti-immunoglobin G (IgG), A, M, total kappa, and lambda]. Due to the presence of an isolated lambda monoclonal band, we analyzed anti-immunoglobin D, anti-IgE, and anti-free light chains. IF revealed a wide IgEλ band in addition to a clonal IgGλ band, estimated at 4.3 g/L and 1 g/L, respectively, on SPE densitometry scan, with barely detectable lambda monoclonal free light chains. Reduction of the sample with betamercaptoethanol led to a more focused ϵ-band that aligned with the lambda band, suggesting monoclonality.

We found a low level of serum immunoglobin M at 0.19 g/L (RV: 0.5–1.65 g/L), normal IgG 8.15 g/L (RV: 6.6–13.0 g/L), immunoglobin A 0.76 g/L (RV: 0.75–3.5 g/L), and β2-microglobulin levels 1.72 mg/L (RV: 0.7–1.8 mg/L) by nephelometry (reagents Siemens®, BNII). Ionized calcium was 4.96 mg/dL (1.24 mmol/L) (RV: 4.60–5.09 mg/dL; 1.15–1.27 mmol/L). To investigate the high level of total IgE, dilutions of serum at 1:1000 and 1:5000 revealed consistent IgE concentrations at 1 672 000 kU/L (4.01 g/L) and 1 550 000 kU/L (3.72 g/L), respectively. The presence of interferents (cryoglobulin and immunoglobin M rheumatoid factor) was excluded. Urine immunofixation showed a Bence–Jones protein λ with a total proteinuria of 0.23 g/L (Cobas 8000, TPUC3, Roche).

We measured serum free light chains (sFLC) by nephelometry with Siemens (N-latex FLC, BNII). We found λ sFLC at 1050 mg/L (RV: 8–27 mg/L), κ sFLC at 13.5 mg/L (RV: 7–22 mg/L), and κ/λ ratio at 0.013 (RV: 0.31–1.56). Titers of sFLC were not fully consistent with the IF, showing virtually absent λ sFLC (Fig. 1C). We therefore measured sFLC by turbidimetry with Freelite® (Optilite, Binding Site) with λ sFLC at 246.16 mg/L (RV: 5.7–26.2 mg/L) and κ sFLC at 10.5 mg/L (RV: 3.3–19.4 mg/L). The result of manual dilution of the sample with Freelite excluded prozone/antigen excess (data not shown).

Bone marrow aspiration identified the presence of 7.5% mature plasmocytes with flaming cytoplasm. Flow cytometry targeted on CD38/CD138 plasmocytes showed that 40% of them expressed CD56, 79% expressed a loss of CD19, and 94% were positive for intracytoplasmic λ light chain (vs 3% for κ light chain). Karyotype analysis and molecular biology showed a t(11; 14) CCND1-IGH translocation. In the absence of clinical and biological criteria for multiple myeloma (MM), a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) of IgEλ and IgGλ isotype was established and medical follow-up was organized in the clinical hematology ward.

Six months later, repeat SPE and IF displayed the same IgE and IgG bands and total IgE was still >5000 kU/L. λ sFLC was measured at 1380 mg/L and κ sFLC at 12.5 mg/L (N-latex, BNII, Siemens). A second bone marrow aspiration identified 6.5% of mature plasmocytes, 39% expressing CD56, 93.5% expressing a loss of CD19, 9% kappa, and 79% lambda intracytoplasmic light chains.