scholarly journals Value of antibodies to free light chains in immunoperoxidase studies of renal biopsies

2014 ◽  
Vol 67 (8) ◽  
pp. 661-666 ◽  
Author(s):  
Mared P Owen-Casey ◽  
Rosalind Sim ◽  
H Terence Cook ◽  
Candice A Roufosse ◽  
Julian D Gillmore ◽  
...  
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Immunoperoxidase Method ◽  
Paraffin Sections ◽  
Free Light Chains ◽  
Light Chain Deposition Disease ◽  
Renal Biopsies ◽  
Light Chain Deposition ◽  
Al Amyloid

AimsBecause immunoglobulin abnormalities may affect the kidney, investigation of renal biopsies requires immunohistological study of light chains. A problem is that most antibodies to light chains react with whole immunoglobulins as well as free light chains, and there are generally many more whole immunoglobulins than free light chains. The usefulness of antibodies that only detected free light chains was investigated.MethodsAntibodies to free light chains were used in an immunoperoxidase method on paraffin sections of 198 renal biopsies, and compared with conventional antibodies against light chains examined by immunofluorescence on 13 frozen sections and by immunoperoxidase on 46 paraffin sections.ResultsImmunofluorescence and immunoperoxidase were concordant on 10 of 13 biopsies. Immunofluorescence detected slight deposition of light chains in three biopsies not shown by immunoperoxidase, of undetermined clinical significance. Using immunoperoxidase, the free light chain antibodies were more sensitive than conventional antibodies, giving much cleaner staining and better detection of deposits in AL amyloid, light chain deposition disease and cryoglobulinaemic glomerulonephritis. The free light chain antibodies showed discordance or ambiguity between immunohistological and clinical findings in seven (4%) of 185 patients with known immunoglobulin status. These included two of 28 cases of AL amyloid that showed no light chain deposition. The method was not designed for detection of light chain restriction in neoplastic plasma or lymphoplasmacytic cells.ConclusionsPolyclonal antibodies to free light chains are an improvement on conventional antibodies in immunoperoxidase study of paraffin sections of renal biopsies and are useful in everyday practice.

scholarly journals Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Bappa Adamu ◽  
Mushabab Al-Ghamdi ◽  
Mustafa Ahmad ◽  
Khaled O. Alsaad
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Cell Transplant ◽  
Free Light Chains ◽  
Light Chain Deposition Disease ◽  
Serum Free ◽  
Deposition Disease ◽  
Serum Free Light Chains ◽  
Light Chain Deposition ◽  
Saudi Male

Light chain deposition disease (LCDD) is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

scholarly journals Complete Primary Sequences of Two λ Immunoglobulin Light Chains in Myelomas with Nonamyloid (Randall-Type) Light Chain Deposition Disease

1998 ◽  
Vol 153 (1) ◽  
pp. 313-318 ◽  
Author(s):  
Catherine Decourt ◽  
Guy Touchard ◽  
Jean-Louis Preud'homme ◽  
Ruben Vidal ◽  
Hélène Beaufils ◽  
...  
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Lambda monoclonal free light chain abnormalities detected by a serum immunofixation electrophoresis assay are underrepresented by quantitative serum free light chain results

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Rebecca Treger ◽  
Kathleen Hutchinson ◽  
Andrew Bryan ◽  
Chihiro Morishima
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Sample Population ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
High Concordance ◽  
Polyclonal Antisera

Abstract Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (<2.63mg/dL) and KLR results (>0.26 & <1.65) were found in samples with distinct lambda monoclonal free light chains visualized by IFIX (X-LMFLC). To investigate this discordance, contemporaneous SFLC or KLR values were evaluated for their ability to accurately classify monoclonal FLCs identified by IFIX. We performed a retrospective analysis of serum and urine IFIX (Sebia Hydrasys) and SFLC (Freelite®, Binding Site) results from our institution between July 2010 through December 2020, using R 4.0.2 and Tidyverse packages. From among 9,594 encounters in which a single monoclonal component was initially identified by IFIX, 157 X-LMFLC and 131 X-KMFLC samples were analyzed. Elevated LFLC with normal KFLC was identified in 105/157 X-LMFLC samples (67%), while both LFLC and KFLC were elevated in 42/157 samples (27%). Concordance between X-KMFLC and KFLC was markedly higher, where 122/131 samples (93%) displayed elevated kappa FLC (>1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR > or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.

scholarly journals In-house age-specific reference ranges for free light chains measured on the SPAPlus® analyser

2020 ◽  
Vol 57 (2) ◽  
pp. 138-143
Author(s):  
Lauren Campbell ◽  
Dawn Simpson ◽  
Adrian Shields ◽  
Berne Ferry ◽  
Karthik Ramasamy ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Light Chain ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Free Light Chain ◽  
Light Chains ◽  
Reference Ranges ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain

Background The measurement of monoclonal free light chains is being increasingly utilized since the introduction of serum-based assays. It is important for laboratories to determine their own reference ranges in order to reflect the local population. The aim of this study was to determine if age-adjusted reference ranges for serum free light chains would have implications for demand management of further laboratory investigations including immunofixation. Methods After certain exclusions, 4293 samples from individuals seen in primary care across Oxfordshire between 2014 and 2016 were identified for analysis of patient characteristics, serum free light chain results and estimated glomerular filtration rate. Results We found age to be an independent variable when considering serum free light chain concentrations, ratio and estimated glomerular filtration rate. The reference ranges derived from our data differ markedly from the original Binding Site ranges. When the age-specific ranges are retrospectively applied to our population, there is a 38% decrease in follow-up testing with no loss of specificity. Conclusion We feel confident implementing new age-specific serum free light chain reference ranges in our laboratory. We have developed a simple algorithm for evaluating serum free light chains based on age and estimated glomerular filtration rate. We encourage laboratories to establish their own local reference ranges using large cohorts and their chosen serum free light chain assay platform.

scholarly journals Serum Reference Intervals and Diagnostic Ranges for Free κ and Free λ Immunoglobulin Light Chains: Relative Sensitivity for Detection of Monoclonal Light Chains

2002 ◽  
Vol 48 (9) ◽  
pp. 1437-1444 ◽  
Author(s):  
Jerry A Katzmann ◽  
Raynell J Clark ◽  
Roshini S Abraham ◽  
Sandra Bryant ◽  
James F Lymp ◽  
...  
Keyword(s):  
Light Chain ◽  
Reference Intervals ◽  
Systemic Amyloidosis ◽  
Light Chains ◽  
Light Chain Deposition Disease ◽  
Monoclonal Gammopathies ◽  
Automated Immunoassay ◽  
Light Chain Deposition ◽  
Diagnostic Intervals ◽  
Detection And Quantification

Abstract Background: The detection of monoclonal free light chains (FLCs) is an important diagnostic aid for a variety of monoclonal gammopathies and is especially important in light-chain diseases, such as light-chain myeloma, primary systemic amyloidosis, and light-chain-deposition disease. These diseases are more prevalent in the elderly, and assays to detect and quantify abnormal amounts of FLCs require reference intervals that include elderly donors. Methods: We used an automated immunoassay for FLCs and sera from a population 21–90 years of age. We used the calculated reference and diagnostic intervals to compare FLC results with those obtained by immunofixation (IFE) to detect low concentrations of monoclonal κ and λ FLCs in the sera of patients with monoclonal gammopathies. Results: Serum κ and λ FLCs increased with population age, with an apparent change for those >80 years. This trend was lost when the FLC concentration was normalized to cystatin C concentration. The ratio of κ FLC to λ FLC (FLC K/L) did not exhibit an age-dependent trend. The diagnostic interval for FLC K/L was 0.26–1.65. The 95% reference interval for κ FLC was 3.3–19.4 mg/L, and that for λ FLC was 5.7–26.3 mg/L. Detection and quantification of monoclonal FLCs by nephelometry were more sensitive than IFE in serum samples from patients with primary systemic amyloidosis and light-chain-deposition disease. Conclusions: Reference and diagnostic intervals for serum FLCs have been developed for use with a new, automated immunoassay that makes the detection and quantification of monoclonal FLCs easier and more sensitive than with current methods. The serum FLC assay complements IFE and allows quantification of FLCs in light-chain-disease patients who have no detectable serum or urine M-spike.

Light-chain deposition disease

2018 ◽  
Author(s):  
Dirk R. J. Kuypers ◽  
Morie A. Gertz
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Renal Involvement ◽  
Bone Marrow Examination ◽  
Therapeutic Monitoring ◽  
Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Light-chain deposition disease (LCDD) is characterized by extracellular tissue deposition of non-amyloid monoclonal immunoglobulin light chains (predominantly kappa light chains) in various organs including kidneys, heart, and liver. It is a rare cause of renal insufficiency. In two-thirds of cases it is associated with multiple myeloma, while in the remainder their monoclonal B cell proliferation does not meet the criteria for that diagnosis.Renal involvement occurs almost invariably and dominates the clinical course of the disease: greater than 90% of patients with LCDD have renal functional impairment; acute or rapidly progressive kidney failure usually develops over a period of months. Nephrotic-range proteinuria is present in 40–50% of patients while approximately 20% of patients develop nephrotic syndrome. Arterial hypertension and microscopic haematuria can be present. Extrarenal symptoms are related to affected organs with cardiomyopathy, cachexia, haemorrhages, infections, and MM progression as main causes of death.The diagnosis of LCDD is often delayed and whilst bone marrow examination will often identify associated MM, renal biopsy frequently provides the final diagnostic proof. Abnormal light chains can be detected and quantified by serum or urine protein electrophoresis and immunofixation. Quantification of urine and serum free kappa/lambda light chains has proven a useful screening tool and might also plays a role in therapeutic monitoring.Treatment consists of chemotherapy directed against the monoclonal immunoglobulin-producing plasma cells.

Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2900-2902 ◽  
Author(s):  
Mark Drayson ◽  
Lian X. Tang ◽  
Roger Drew ◽  
Graham P. Mead ◽  
Hugh Carr-Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Activity ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Using sensitive, automated immunoassays, increased concentrations of either κ or λ free light chains (and abnormal κ/λ ratios) were detected in the sera of 19 of 28 patients with nonsecretory multiple myeloma. Four other patients had suppression of one or both light chains, and the remaining 5 sera had normal or raised free light-chain concentrations with substantially normal κ/λ ratios. Six of the patients with an elevated single free light chain, who were studied during follow-up, had changes in disease activity that were reflected by the changes in free light-chain concentrations. It is concluded that quantification of free light chains in serum should prove useful for the diagnosis and monitoring of many patients with nonsecretory myeloma.

scholarly journals Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Aurélie Grados ◽  
Mikael Ebbo ◽  
José Boucraut ◽  
Frédéric Vély ◽  
Pierre Aucouturier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Lupus Erythematosus ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Related Disease ◽  
Serum Free Light Chain ◽  
Igg4 Related Disease

Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that theκ() andλ() free light chains and theκ : λratio () are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase ofκandλfree light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

Sign in / Sign up

Export Citation Format

Share Document