Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Light chain myeloma and detection of free light chains in serum and urine of dogs and cats.

ABSTRACT:

Background

Detection of free light chains (fLC) in animals relies on protein electrophoresis or the Bence-Jones protein test on urine.

Objective

To describe the detection of both serum fLC (sfLC) and urine fLC (ufLC) in 8 dogs and 2 cats using a commercially available human immunofixation (IF) kit.

Animals

Archived serum or urine samples from 27 dogs and 2 cats submitted to the Colorado State University Veterinary Diagnostic Laboratory for routine diagnostics.

Methods

Retrospective study evaluating the presence of fLC in dogs and cats using agarose gel electrophoresis and routine and fLC IF performed on serum and urine. The performance of the fLC IF reagents was evaluated using samples characterized by routine IF, tandem mass spectrometry, and a combination of fLC IF and western blotting. Free light chains were documented by paired electrophoresis and fLC IF.

Results

The fLC only myeloma case developed end-stage renal failure 5 months post initial diagnosis. All electrophoresis-defined urinary Bence-Jones proteins were labeled by the anti-free λ light chain (anti-fλ) reagent; none were labeled by the anti-free κ light chain (anti-fκ); 2 of these were identified as fκ by mass spectrometry. An electrophoretically identical protein restriction that was labeled by the anti-fλ reagent was present in the paired serum from 5/8 of cases, documenting sfLC.

Conclusions and clinical importance

Commercially available human IF reagents identified sfLC and ufLC in both dogs and cats. Free light chains may be nephrotoxic in dogs.

SUBMITTER: Harris RA

PROVIDER: S-EPMC7995444 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma.

Project description:Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.

| S-EPMC5179336 | biostudies-literature

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

Project description:Response criteria for multiple myeloma are based upon changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis. The latter lacks sensitivity at low monoclonal protein levels and since 2001, the serum free light chain test has been available and its clinical utility proven, yet guidelines have not recommended it as a replacement for urine assessment. Herein we evaluated responses using serum free light chain measurements and serum and urine electrophoresis after 2 and 4 cycles of therapy and after stem cell transplantation in 25 light chain and 157 intact immunoglobulin myeloma patients enrolled in the IFM 2007-02 MM trial. All 25 light chain patients had measurable disease by serum free light chain and urine methods at presentation. By contrast 98 out of 157 intact immunoglobulin patients had measurable disease by serum free light chain compared to 55 out of 157 by urine electrophoresis. In all patients there was substantial agreement between predicate (serum/urine protein electrophoresis) and test (serum protein electrophoresis and serum free light chain) methods for response assessment (Weighted Kappa=0.83). Urine immunofixation became negative in 47% light chain and 43% intact immunoglobulin patients after 2 cycles of therapy. At this time the serum free light chain ratio normalised in only 11% and 27% patients, respectively. In summary we found good agreement between methods for response assessment, but the serum free light chain test provided greater sensitivity than urine electrophoresis for monitoring. To our knowledge this is the first report comparing both methods for response assignment based on the International Myeloma Working Group guidelines. (Clinical Trials Register.eu identifier: 2007-005204-40).

| S-EPMC4815727 | biostudies-literature

Can urine studies be replaced by serum free light chains measurements to assign responses in multiple myeloma patients?

Project description:Serum and urine protein electrophoresis and immunofixation are the preferred techniques for monitoring monoclonal proteins and evaluating treatment response in multiple myeloma (MM) patients with measurable disease. However, urine studies are subjected to limitations that may lead to inaccuracies or prevent guidelines compliance. We retrospectively studied if the substitution of urine studies by measuring serum free light chains (sFLCs) results in a comparable disease monitoring, both in intact immunoglobulin (II) and light chain (LC) MM patients. In our cohort, equal or higher percentages of disease were identified by sFLCs at baseline and maximum response as compared to urine studies. Achieving very good partial response or better (≥VGPR) according to the response criteria proposed by the French group (evaluating sFLCs instead of urine) and the IMWG response criteria were associated to a 62% and 63% reduced risk of progression, respectively. A similar prognostic value for reaching ≥VGPR was also observed among LCMM patients when the French group and the IMWG response criteria were applied. Overall, these results support the replacement of urine studies by the sFLCs assay in IIMM. In LCMM, sFLCs could be used for monitoring and urine studies could be performed only to confirm complete remissions and progressions.

| S-EPMC9748693 | biostudies-literature

Comparison of serum and urine free light chain analysis in clinical diagnosis.

Project description: Not available

| S-EPMC9812726 | biostudies-literature

Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials.

Project description:We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.

| S-EPMC6128544 | biostudies-literature

Urine and Free Immunoglobulin Light Chains as Analytes for Serodiagnosis of Hantavirus Infection.

Project description:Rapid point-of-care testing is a megatrend in infectious disease diagnosis. We have introduced a homogeneous immunoassay concept, which is based on the simultaneous binding of antigen and protein L to a given immunoglobulin molecule. The complex formation is detected utilizing time-resolved Förster resonance energy transfer between antigen-attached donor and acceptor-labeled protein L, hence the name LFRET. Here, we demonstrate that urine can be used as a sample matrix in LFRET-based serodiagnostics. We studied urine samples collected during the hospitalization and recovery of patients with acute Puumala orthohantavirus (PUUV) infection. We compared PUUV antibody-specific LFRET signals in urine to those in plasma, and found excellent correlation in the test outcomes The LFRET test from urine was positive in 40/40 patients with acute PUUV infection. PUUV causes a mild form of hemorrhagic fever with renal syndrome, characterized by acute kidney injury and proteinuria. Immunofluorescence and western blotting demonstrated PUUV-IgG and -IgA in urine, however, the presence of intact immunoglobulins did not fully explain the LFRET signals. We purified free light chains (FLCs) from both urine and serum of healthy volunteers and patients with acute PUUV infection, and verified the presence of antigen-specific FLCs. Antigen-specific FLCs provide a new means for non-invasive antibody detection and disease diagnosis.

| S-EPMC6783946 | biostudies-literature

Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy.

Project description:Normalization of the serum-free light-chain ratio (FLCr) with the absence of bone marrow monoclonal plasma cells following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma (MM), and is associated with improved overall survival (OS). However, its value in patients achieving <CR is not clear. We hypothesized that patients achieving a normalization of FLCr with initial therapy of MM will have an improved outcome, even in the absence of a CR. We retrospectively evaluated 449 patients with newly diagnosed MM with measurable disease at baseline, who did not achieve a CR with initial therapy. One hundred and fifty-three patients (34%) had a normal FLCr, whereas 296 (66%) had an abnormal ratio. Patients with a normal FLCr had a longer progression-free survival (29 vs 16 months, P<0.001) and OS (91 vs 58 months, P<0.001). Normalization of FLCr retained its prognostic value in a multivariable model. Our results suggest an important role for sFLC measurement in disease monitoring even in patients who achieve only a partial response to therapy. Obtaining a normal FLCr confers a favorable prognosis independent from other factors, supporting the inclusion of sFLC in all levels of response criteria.

| S-EPMC4598254 | biostudies-literature

Comparison of three different serum-free light-chain assays-implications on diagnostic and therapeutic monitoring of multiple myeloma.

Project description:The measurement of serum-free light chains (FLC) is standard of care in the diagnosis and management of multiple myeloma (MM). The revised international myeloma working group (IMWG) implemented the involved FLC/noninvolved FLC (iFLC/niFLC) ratio as a biomarker for MM requiring treatment. Recently, a new definition of high-risk smoldering MM (SMM) including iFLC/niFLC ratio was published. These recommendations were solely based on a single assay method (Freelite assay). Today, two additional assays, N Latex FLC and ELISA-based Sebia FLC, are available. Here, we report on a single-center-study comparing results of all three different assays for FLC correlation and its potential implications for diagnostic and clinical use. In total, 187 samples from 47 MM patients were examined, and determination of FLC was performed. Comparison analyses showed similar FLC results for Sebia FLC and N Latex FLC assay with markedly lower absolute values for κ/λ ratio compared with Freelite. Values of λ FLC exhibited high variability. The ratio of iFLC/niFLC showed significant discrepancies among these assays. Our data demonstrate that the three available assays may result in markedly discrepant results, and should not be used interchangeably to monitor patients. Furthermore, modifications of the assay-specific diagnostic (iFLC/niFLC) thresholds for SMM and MM are recommended.

| S-EPMC6949235 | biostudies-literature

Circulating serum free light chains as predictive markers of AIDS-related lymphoma.

Project description:PURPOSE HIV-infected persons have an elevated risk of developing non-Hodgkin's lymphoma (NHL); this risk remains increased in the era of effective HIV therapy. We evaluated serum immunoglobulin (Ig) proteins as predictors of NHL risk among HIV-infected individuals. PATIENTS AND METHODS By using three cohorts of HIV-infected persons (from 1982 to 2005), we identified 66 individuals who developed NHL and 225 matched (by cohort, sex, ethnicity, age, and CD4 count), HIV-infected, lymphoma-free controls who had available stored prediagnostic blood samples. Serum/plasma samples obtained 0 to 2 years and 2 to 5 years before diagnosis/selection were assayed for IgG, IgM, and IgA levels; monoclonal (M) Igs; and kappa and lambda free light chain (FLC) levels. Patients and matched controls were compared by using conditional logistic regression. Results The kappa and lambda FLCs were both significantly higher in patients (eg, in 2- to 5-year window: median kappa, 4.24 v 3.43 mg/dL; median lambda, 4.04 v 3.09 mg/dL) and strongly predicted NHL in a dose-response manner up to 2 to 5 years before diagnosis/selection (eg, NHL risk 3.76-fold higher with kappa concentration at least 2.00 times the upper limit of normal, and 8.13-fold higher with lambda concentration at least 2.00 times the upper limit of normal compared with normal levels). In contrast, IgG, IgM, and IgA levels were similar in patients and controls. M proteins were detected in only two patients with NHL (3%) and in nine controls (4%), and they were not significantly associated with NHL risk. CONCLUSION Elevated FLCs may represent sensitive markers of polyclonal B-cell activation and dysfunction and could be useful for identifying HIV-infected persons at increased NHL risk.

| S-EPMC2834393 | biostudies-literature

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

Project description: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 cut-off 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 cut-off of sum κ + λ 16.7 with diagnostic application in CVID patients, and discuss potential specific defects converging in low or undetectable sFLC.

| S-EPMC7431983 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data