Analytical Criticalities Associated to Different Immunological Methods for Serum Free Light Chain Detection in Plasma Cell Dyscrasias: A Description of Particular Clinical Cases

Sabatino, Rocco; Perrone, Antonio; Cuomo, Marco; Liotti, Sandra; Barchiesi, Vittoria; Cantile, Monica; Cavalcanti, Ernesta

doi:10.3390/ijms18040804

Cited by 4 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, we could not include an active control group of subjects with acute viral and/or bacterial infections. Finally, our analytical method was consistent with previously reported studies [ 2 , 9 ], but we acknowledge that it may not be the optimal one [ 43 ]. For these reasons, at the present time, we cannot suggest that the determination of FLCs has clinical relevance, with a cost/benefit ratio justifying its use in MG clinical management.…”

Section: Discussionsupporting

confidence: 87%

Serological Immunoglobulin-Free Light Chain Profile in Myasthenia Gravis Patients

Basile

Marino

Napodano

et al. 2018

Journal of Immunology Research

View full text Add to dashboard Cite

Background Serological levels of free immunoglobulin light chains (FLCs), produced in excess of heavy chains during synthesis of immunoglobulins by plasma cells, can be considered a direct marker of B cell activity in different systemic inflammatory-autoimmune conditions and may represent a useful predictor of rituximab (RTX) therapeutic efficacy, as reported for rheumatoid arthritis and systemic lupus erythematosus. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction with antibodies (abs) targeting the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK), inducing muscle weakness and excessive fatigability. As MG course may be remarkably variable, we evaluated the possible use of FLCs as biomarkers of disease activity. Subjects and Methods We assessed FLC levels in 34 sera from 17 AChR-MG and from 13 MuSK-MG patients, in comparison with 20 sera from patients with systemic autoimmune rheumatic diseases and 18 from healthy blood donors, along with titers of specific auto-abs and IgG subclass distribution. Results We found a statistically significant increase in free κ chains in both AChR- and MuSK-MG patients, while free λ chain levels were increased only in AChR-MG. We also observed a significant reduction of both free κ and λ chains in 1/4 MuSK-MG patients along with specific abs titer, two months after RTX treatment. Conclusions From our data, FLCs appear to be a sensitive marker of B cell activation in MG. Further investigations are necessary to exploit their potential as reliable biomarkers of disease activity.

show abstract

Section: Discussionsupporting

confidence: 87%

Serological Immunoglobulin-Free Light Chain Profile in Myasthenia Gravis Patients

Basile

Marino

Napodano

et al. 2018

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…The difference observed in FLC lambda results in three multiple myeloma patients should not be overlooked. Similar discrepancies between two tests have also been described in previous evaluations ( 17 , 18 ). Messiaen AS et al .…”

Section: Discussionsupporting

confidence: 89%

Verification study of free light chains assays on reagent-optimized analysers

Šegulja

Matišić

Barišić

et al. 2019

Biochem. med. (Online)

View full text Add to dashboard Cite

Introduction: Our aim was to compare analytical specifications of two assays (monoclonal vs. polyclonal) for free light chains (FLCs) quantification optimized for two different analytical platforms, nephelometer ProSpec (Siemens, Erlangen, Germany) and turbidimetric analyser Optilite (The Binding Site, Birmingham, UK). Materials and methods: The evaluation included verification of the precision, repeatability and reproducibility, estimation of accuracy and method comparison study with 37 serum samples of haematological patients. Kappa and lambda FLC were measured in each sample by both methods and kappa/lambda ratio was calculated. Results: Results show satisfactory precision of both methods with coefficients of variation for ProSpec of CVwr = 2.20% and CVbr = 3.44%, and for Optilite CVwr = 2.82% and CVbr = 4.15%. Estimated bias for FLC lambda was higher on the ProSpec analyser, but bias for FLC kappa was higher on the Optilite analyser. Correlation coefficients were 0.98; P < 0.001 for FLC kappa and 0.97; P < 0.001 for FLC lambda. Considering normal/pathological FLC ratio moderate agreement within assays was detected (κ = 0.621). When the results were categorized according to criteria for progressive disease, 4/37 (0.10) cases were differently classified. Lambda FLC values by Optilite in three samples with monoclonal FLC lambda were more than twelve times higher than by ProSpec. A 25% difference in FLC ratio was detected in 16/37 (0.43) and 50% difference in 13/37 (0.35) patients. Conclusions: All manufacturers’ precision claims could not be achieved in the verification study. The comparison of results to biological variations data showed that coefficients of variations are acceptable for both assays. The assays should not be used interchangeably in haematological patients.

show abstract

“…sFLC quantification may indicate the presence of B cell clonality and is widely used in clinical practice for the diagnosis of B-cell lymphoproliferative disorders (B-CLPD), in particular the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), as well as a marker of neuroinflammation, for instance, in multiple sclerosis (16)(17)(18)(19)(20)(21)(22)(23). Moreover, dysbalance in sFLC is used as a prognostic marker of various B-CLPD, such as chronic lymphocytic leukemia (CLL), B cell non-Hodgkin lymphomas (NHL), as well as for real-time monitoring of response to treatment and disease progression (5,17,(24)(25)(26)(27). Due to the inherent immunological alterations in a relevant proportion of PID patients, such as polyclonal B cell proliferation, it is particularly challenging to make an early diagnosis of B malignancy in these patients.…”

Section: Background: Immunoglobulin the Master Key Of Many Locksmentioning

confidence: 99%

Serum Free Immunoglobulins Light Chains: A Common Feature of Common Variable Immunodeficiency?

et al. 2020

View full text Add to dashboard Cite

Serum free light chain (sFLC) is a recently proposed biomarker for CVID diagnosis. Most CVID patients present low or undetectable sFLC up to 10-fold lower compared to other primary antibody deficiencies. Given that κ and λ light chains are normally secreted in excess with respect to immunoglobulins, this finding points to an intrinsic defect of B cell differentiation in CVID. sFLC levels were prospectively evaluated in a cohort of 100 primary immunodeficiency (PID) patients and in 49 patients with secondary immunodeficiency to haematological malignancy (SID). CVID patients had significantly lower κ and/or λ values (mean: κ: 1.39 ± 1.7 mg/L and λ: 1.97 ± 2.24 mg/L) compared to "other PIDs" (κ: 13.97 ± 5.88 mg/L and λ: 12.92 ± 7.4 mg/L, respectively, p < 0.001 both), and SID (κ 20.9 ± 22.8 mg/L and λ 12.8 ± 8.7 mg/L, respectively, p < 0.001 both). The sum of kappa and lambda (sum κ + λ) in CVID patients (7.25 ± 7.90 mg/L) was significantly lower respect to other PIDs (26.44 ± 13.25 mg/L, p < 0.0001), and to SID patients (28.25 ± 26.24 mg/L, p = 0.0002). ROC analysis of the sum κ + λ disclosed an area under the curve (AUC) of 0.894 for CVID diagnosis (SD 0.031; 95% CI: 0.83-0.95, p < 0.0001), with optimal cutoff of 16.7 mg/L, giving the highest combination of sensitivity (92%), specificity (75%) and NPV (98%). The Relative Risk (RR) for patients presenting a sum κ + λ below 16.7 mg/L was 20.35-fold higher (95%, CI: 5.630-75.93) for CVID than below this threshold. A similar behavior of the sFLC in our CVID cohort with respect to previously published studies was observed. We propose a cutoff of sum κ + λ 16.7 with diagnostic application in CVID patients, and discuss potential specific defects converging in low or undetectable sFLC.

show abstract

Analytical Criticalities Associated to Different Immunological Methods for Serum Free Light Chain Detection in Plasma Cell Dyscrasias: A Description of Particular Clinical Cases

Cited by 4 publications

References 38 publications

Serological Immunoglobulin-Free Light Chain Profile in Myasthenia Gravis Patients

Serological Immunoglobulin-Free Light Chain Profile in Myasthenia Gravis Patients

Verification study of free light chains assays on reagent-optimized analysers

Serum Free Immunoglobulins Light Chains: A Common Feature of Common Variable Immunodeficiency?

Contact Info

Product

Resources

About