Search

This article discusses the establishment of serum free light chains (sFLC) reference intervals for the Lebanese population, highlighting concerns about the universality of standard reference ranges. The study collected 149 blood samples from healthy adults in Lebanon and found statistically significant variations in free kappa and lambda levels across different age groups. Applying the proposed revised reference intervals decreased overdiagnosis of plasma cell disorders, emphasizing the importance of population-specific reference ranges. The study also addresses methodological variables and analytical contributors to the variability in sFLC results, advocating for standardized reference methods and updated assay developments for accurate diagnosis and monitoring. [Extracted from the article]

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel. [ABSTRACT FROM AUTHOR]

Background A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients. Methods Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department. Results There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P <.001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B. Conclusions Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal. [ABSTRACT FROM AUTHOR]

Abstract Background The prognosis of patients with light‐chain amyloidosis (AL) has improved markedly in the past decade in China; whether the current staging systems are suitable to predict the overall survival (OS) of the patients remains undetermined. Methods Based on 980 biopsy‐proved AL patients with 5‐year follow‐up from China Registration Network for Light‐chain Amyloidosis, we evaluated the efficacy of existing staging systems and developed a new stratification model. This involved analyzing parameters such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) thresholds and estimated glomerular filtration rate (eGFR). Results We found that 30% patients were classified as stage I, 25% as stage II, 26% as stage III, and 19% as stage IV disease using the Mayo 2012 staging system, with varying median OS values. However, the observed median OS values were notably higher than previously reported. By incorporating NT‐proBNP thresholds and eGFR values, we developed a four‐stage score system. With this new model, 41.6% patients were reclassified to stage I, 34.3% to stage II, 17.8% to stage III, and 6.3% to stage IV disease, with adjusted median OS values. Conclusion The new stratification model exhibited improved consistency compared to traditional staging systems. It effectively identified patients with the best and worst prognoses, even among those receiving comprehensive treatment. Specifically, NT‐proBNP levels exceeding 9000 pg/mL combined with an eGFR less than 60 mL/min/1.73 m2 proved superior in prognosticating patient outcomes. Overall, the median OS of AL amyloidosis patients in China has significantly improved, underscoring the need for tailored prognostic models in clinical practice.

Background Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, little is known about the consequences of MGUS on long-term outcomes. Methods We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls. Results Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P  = .03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P  = .007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P  = .04) and a trend for more bacterial infections (63% vs 48%, P  = .08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival. Conclusions MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression. [ABSTRACT FROM AUTHOR]

Keywords: proficiency testing; reference interval; serum free light chains EN proficiency testing reference interval serum free light chains e229 e232 4 10/03/23 20231001 NES 231001 To the Editor, Serum immunoglobulin free light chain (FLC) measurement has become an important component for diagnosis and management of patients with clonal plasma cell and B-cell proliferative disorders. Although the magnitude of involved to uninvolved FLCr is a factor as one of the myeloma-defining events, the International Myeloma Working Group (IMWG) diagnostic [[1]] and response [[2]] criteria also include any abnormal FLCr as potentially significant. Graph: Figure 1: Distribution of serum Kappa/Lambda FLC ratios (FLCr) reported by proficiency testing participants. Individual serum FLCr reported for specimen SFLC-01 by participants in the SFLC-A 2019 proficiency testing survey are shown, grouped and color-coded by reagent and instrument manufacturer. [Extracted from the article]

Background: The aim was to explore the diagnostic value of serum free light chain (sFLC) and other laboratory indicators for the patients with light chain multiple myeloma (LCMM). Methods: We performed a retrospective study including 82 LCMM cases and 43 healthy subjects as the observation and control groups, respectively. The observation group was further divided into two subgroups: κ- and λ- type LCMM. Sixteen quantitative indicators were collected and the difference among groups was compared. We also evaluated the positive detection rate (PDR) of four qualitative indicators for M protein detection. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of sixteen indicators. Results: Fourteen indicators showed statistical differences between the control group and κ- or λ-type LCMM subgroup. The κ and λ sFLC ratio (rFLC) and the difference between κ and λ FLC (dFLC) showed differences among the three groups. Among the four qualitative indicators of M protein detection, rFLC showed the highest PDR for both κ- and λ-type LCMM. Among the three combinations with rFLC or uIFE did not show statistical differences. ROC curve analysis indicated a relatively high diagnostic value of dFLC for both κ- and λ-type LCMM. Conclusions: We should be vigilant about the missed diagnosis by observing the changes of MM-related indicators, particularly dFLC and the six other indicators with high diagnostic value. rFLC can improve the diagnostic ability of LCMM. [ABSTRACT FROM AUTHOR]

Serum κ and λ free light chains can be markedly elevated in monoclonal gammopathies; consequently, serum free light chain (sFLC) immunoassays are susceptible to inaccuracies caused by antigen excess. As a result, diagnostics manufacturers have attempted to automate antigen excess detection. A 75-year-old African-American woman had laboratory findings consistent with severe anemia, acute kidney injury, and moderate hypercalcemia. Serum and urine protein electrophoresis and sFLC testing were ordered. The sFLC results initially showed mildly elevated free λ light chains and normal free κ. The pathologist noted that sFLC results were discrepant with the bone marrow biopsy, electrophoresis, and immunofixation results. After manual dilution of the serum, repeat sFLC testing revealed significantly higher λ sFLC results. Antigen excess causing falsely low sFLC quantitation may not be detected by immunoassay instruments as intended. Correlation with clinical history, serum and urine protein electrophoresis results, and other laboratory findings is essential when interpreting sFLC results. [ABSTRACT FROM AUTHOR]

Objectives There is considerable variation in ordering practices for the initial laboratory evaluation of monoclonal gammopathies (MGs) despite clear society guidelines to include serum free light chain (sFLC) testing. We assessed the ability of a clinical decision support (CDS) alert to improve guideline compliance and analyzed its clinical impact. Methods We designed and deployed a targeted CDS alert to educate and prompt providers to order an sFLC assay when ordering serum protein electrophoresis (SPEP) testing. Results The alert was highly effective at increasing the co-ordering of SPEP and sFLC testing. Preimplementation, 62.8% of all SPEP evaluations included sFLC testing, while nearly 90% of evaluations included an sFLC assay postimplementation. In patients with no prior sFLC testing, analysis of sFLC orders prompted by the alert led to the determination that 28.9% (800/2,769) of these patients had an abnormal κ/λ ratio. In 452 of these patients, the sFLC assay provided the only laboratory evidence of a monoclonal protein. Moreover, within this population, there were numerous instances of new diagnoses of multiple myeloma and other MGs. Conclusions The CDS alert increased compliance with society guidelines and improved the diagnostic evaluation of patients with suspected MGs. [ABSTRACT FROM AUTHOR]

Background: Our aim was to establish local reference intervals for k and λ free light chains. Methods: Fresh sera from 246 healthy blood donors were analyzed to evaluate reference intervals for FLC. CLSI EP28-A3C protocol was applied to establish new RIs. Results: The 95% reference interval for FLCk was 7.20 - 20.0 mg/L, and that for FLCλ was 6.72 - 20.23 mg/L. The diagnostic interval for the k/λ ratio was 0.5 - 2.11 mg/L. When we analyze the distribution of the k/λ ratio results for the 1,025 pieces of data collected using the diagnostic intervals reported by the manufacturer and those established in this study, we observed that discordant results were reported in 14.5% of patients with MGUS and 16.3% of patients with multiple myeloma. Conclusions: Our findings underline the importance of establishing the reference intervals for serum FLCs and the proper diagnostic interval by instrument platform and appropriate to the target study patient population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Objective Patients with light chain–predominant multiple myeloma have been shown to exhibit shorter survival. Retrospective comparison of clinical and laboratory data was undertaken to ascertain the likely cause(s) of this observation. Methods Records of patients with multiple myeloma seen at 1 institution revealed 316 patients with conventional and 71 patients with light chain–predominant multiple myelomas with secretion of intact immunoglobulins. Laboratory and clinical findings in the 2 groups were compared. Results Patients with light chain–predominant multiple myeloma had a significantly higher death rate, a higher rate of chronic dialysis, a lower estimated glomerular filtration rate and serum albumin, a significantly higher urine protein concentration, and a significantly higher prevalence of hypertension and blood transfusion requirements. Other clinical and laboratory parameters surveyed were not significantly different between the 2 groups. Conclusion The shorter survival of patients with light chain–predominant multiple myeloma is clearly associated with renal damage caused by excess free immunoglobulin light chains. Renal damage may be ameliorated by early aggressive treatment with chemotherapy, plasmapheresis, and dialysis; a multi-institutional prospective controlled trial would be needed to test this hypothesis. [ABSTRACT FROM AUTHOR]

Abstract In nonsecretory, oligo‐secretory, and light chain multiple myeloma patients, serial sFLC evaluation could precede biochemical and clinical disease progression, even in extramedullary relapse, thus initiating early treatment with novel anti‐MM agents.

Introduction: Neoplastic monoclonal gammopathies are frequently associated with production of excess free monoclonal light chains. A sensitive method for detecting free monoclonal light chains in serum could provide a marker for residual/minimal residual disease and as an adjunct to serum protein electrophoresis to serve as a screening method for monoclonal gammopathies. Methods: Conventional serum immunofixation electrophoresis was modified by applying undiluted serum samples, and staining for serum free light chains with antisera specific to free light chains. Washing/blotting of gels was enhanced to remove residual proteins that did not bind to the antibodies including intact monoclonal immunoglobulins. Results from this modified immunofixation electrophoresis were compared with results from commercially available MASS-FIX/MALDI assay. Results: Monoclonal free kappa light chains could be detected to a concentration of about 1.78 mg/L and monoclonal free lambda light chains to a concentration of about 1.15 mg/L without the need for special equipment. Comparison of these thresholds with parallel results from a commercially available MASS-FIX/MALDI assay revealed the modified electrophoretic method to be more sensitive in the context of free monoclonal light chains. Conclusions: Modified serum immunofixation electrophoresis has been shown to detect low levels of monoclonal free light chains at a sensitivity suitable for the method to be used in detecting minimal residual disease, and potentially in a screening assay for monoclonal gammopathies. The disparity in the results with commercially available MASS-FIX/MALDI assay is postulated to be due to limited repertoire of reactivity of nanobodies of camelid origin.

Testing urine for Bence Jones Protein (BJP) had been a time old procedure used for screening and monitoring of monoclonal disorders since its description. However, has poor sensitivity and despite advances in diagnostic methods of monoclonal disorders it is being continued to be requested in individuals for evaluation of myeloma or plasma cell disorders. Effective utilization and minimizing untimely or unnecessary investigations is important in the evaluation and management of any medical condition. Though, we are hard-wired during our education with some "trigger" or "peculiar" words that make us jump to actions too quickly, without comprehending the actual problem. Supporting evidence is presented to avoid reflexive use of multiple tests and utilize tests that improve utilization, reduce waste, and uphold the Choosing Wisely principles in providing optimal care to the patients. [ABSTRACT FROM AUTHOR]

Background: Monoclonal immunoglobulins provide an indication of the tumor burden in patients with plasma cell neoplasms. Higher concentrations of serum free light chains in light chain predominant multiple myeloma have been shown to correlate with a poorer outcome. We examined the correlations of serum free light chain concentrations in light chain myelomas with survival, estimated glomerular filtration rate (eGFR) and other clinical and pathological parameters. Methods: Records of patients with light chain multiple myelomas were reviewed. Highest concentration of serum free light chains for each patient were plotted to ascertain an inflection/change point. Survival, eGFR, and other clinical and pathological parameters were compared between the low and high light chain concentration groups. Results: Plotting serum free light chain concentrations revealed an inflection point at a concentration of 455 mg/L apportioning patients in to 2 subgroups: 39 patients with low light chain concentrations and 26 patients with high concentrations. The high concentration group had more unfavorable pathology in bone marrow examination in terms of higher neoplastic plasma cell burden and high-risk cytogenetics. The survival rate and eGFR in the high concentration group were significantly worse than in the low concentration group. Conclusions: As noted for light chain predominant multiple myeloma, high serum free light chain concentration in light chain multiple myelomas are associated with higher renal disease burden and shorter survival. Monitoring of serum free light chain concentrations and customizing treatments to address this parameter are warranted. [ABSTRACT FROM AUTHOR]

Sera from patients with multiple myeloma usually display a single monoclonal immunoglobulin band on serum protein immunofixation electrophoresis. Multiple bands may be seen if the myeloma is bi- or triclonal or if the monoclonal immunoglobulin has rheumatoid factor activity. We describe a patient with light chain–predominant IgA lambda myeloma; the patient's serum displayed 2 spatially distinct bands reacting for alpha heavy and lambda light chains. The methods used to establish monoclonality are addressed. [ABSTRACT FROM AUTHOR]

The assessment of AL amyloidosis response is based on serum free light chains (sFLC) levels, and serum and urine monoclonal protein investigations. Recently, difference between involved and uninvolved free light chains (dFLC), involved free light chain (iFLC) and complete response (CR) has been reported as independent predictor of survival and a refinement of the hematological response criteria has been proposed by several groups. In the current study, all consecutive newly diagnosed symptomatic AL amyloidosis patients were evaluated. The primary objective of the study was to assess hematological and organ response after first line of treatment. A cohort of 76 cases with upfront treatment was used for this analysis. After a median of 3 months post-therapy, hematological response was seen in 88% of cases including CR in 26.3%, VGPR in 38.2% and PR in 23.7%. Median OS was longer in patients with dFLC < 10 mg/L at 3 months, iFLC <20 mg/L at 1 and 3 months, and those achieving CR. Multivariate analysis showed presence of CR as the most important independent prognostic factors for survival. Our study suggests that maximal sFLC response and CR are potential endpoints to define clinical outcomes. Large collaborative studies are required to validate and optimize response criteria. [ABSTRACT FROM AUTHOR]

Summary: Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in affected individuals as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of κ and λ FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free κ/λ ratio and κ + λ sum (p = 0.0001). SSc patients showed increased free κ in urine with a κ/λ higher than HC (p = 0.0001). SSc patients with increased κ + λ in serum showed that erythro‐sedimentation rate (p = 0.034), C‐reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free κ and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free κ in urine had higher DAI (p = 0.048) than SSc patients with normal κ levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients. [ABSTRACT FROM AUTHOR]

We report on an observational, multicenter study of 345 adult CVID patients, designed to assess the diagnostic value and the clinical association of serum free light chain (sFLC) pattern in Common Variable Immunodeficiency disorders (CVID). Sixty CVID patients were tested twice in order to assess intraindividual variability of sFLC. As control groups we included 138 patients affected by undefined primary antibody defects (UAD), lymphoproliferative diseases (LPDs), and secondary antibody deficiencies not related to hematological malignancies (SID). CVID patients presented lower κ and λ chain concentration compared to controls, showing low intraindividual sFLC variability. On the basis of the sFLC pattern, patients were classified into four groups: κ−λ+, κ+λ−, κ−λ−, κ+λ+. The most common pattern in CVID patients was κ−λ− (51%), followed by κ−λ+, (25%), κ+λ+ (22%), and κ+λ− (3%). In UAD, LPD, and SID groups κ+λ+ was the most common pattern observed. By analyzing the possible association between sFLC patterns and disease-related complications of CVID, we observed that patients belonging to the κ−λ− group presented more commonly unexplained enteropathy compared to the κ+λ+ group and showed higher frequency of bronchiectasis and splenomegaly compared to both the κ−λ+ and κ+λ+ patients. When compared to the other groups, κ−λ− had also lower serum IgG, IgA, and IgM concentrations at diagnosis, lower frequency of CD27+IgD–IgM– switched memory B cells, and higher frequency of CD21low B cells, receiving earlier CVID diagnosis. Thus, lower levels of sFLC might be an epiphenomenon of impairment in B cell differentiation, possibly leading κ−λ− patients to a higher risk for bacterial infections and chronic lung damage. Based on these results, we suggest adding sFLC assay to the diagnostic work-up of hypogammaglobulinemia and during follow-up. The assay may be useful to differentiate CVID from other causes of hypogammaglobulinemia and to early detect monoclonal lymphoproliferation occurring over years. Moreover, since the sFLC pattern seems to be related to disease phenotypes and clinical manifestations of CVID and after confirmation by further studies, sFLC assay might be considered a promising prognostic tool for identifying patients at higher risk of developing enteropathy and chronic lung damage or splenomegaly. This will allow designing a tailored follow-up for CVID patients.

In nonsecretory, oligo‐secretory, and light chain multiple myeloma patients, serial sFLC evaluation could precede biochemical and clinical disease progression, even in extramedullary relapse, thus initiating early treatment with novel anti‐MM agents. [ABSTRACT FROM AUTHOR]

We report on an observational, multicenter study of 345 adult CVID patients, designed to assess the diagnostic value and the clinical association of serum free light chain (sFLC) pattern in Common Variable Immunodeficiency disorders (CVID). Sixty CVID patients were tested twice in order to assess intraindividual variability of sFLC. As control groups we included 138 patients affected by undefined primary antibody defects (UAD), lymphoproliferative diseases (LPDs), and secondary antibody deficiencies not related to hematological malignancies (SID). CVID patients presented lower κ and λ chain concentration compared to controls, showing low intraindividual sFLC variability. On the basis of the sFLC pattern, patients were classified into four groups: κ−λ+, κ+λ−, κ−λ−, κ+λ+. The most common pattern in CVID patients was κ−λ− (51%), followed by κ−λ+, (25%), κ+λ+ (22%), and κ+λ− (3%). In UAD, LPD, and SID groups κ+λ+ was the most common pattern observed. By analyzing the possible association between sFLC patterns and disease-related complications of CVID, we observed that patients belonging to the κ−λ− group presented more commonly unexplained enteropathy compared to the κ+λ+ group and showed higher frequency of bronchiectasis and splenomegaly compared to both the κ−λ+ and κ+λ+ patients. When compared to the other groups, κ−λ− had also lower serum IgG, IgA, and IgM concentrations at diagnosis, lower frequency of CD27+IgD–IgM– switched memory B cells, and higher frequency of CD21low B cells, receiving earlier CVID diagnosis. Thus, lower levels of sFLC might be an epiphenomenon of impairment in B cell differentiation, possibly leading κ−λ− patients to a higher risk for bacterial infections and chronic lung damage. Based on these results, we suggest adding sFLC assay to the diagnostic work-up of hypogammaglobulinemia and during follow-up. The assay may be useful to differentiate CVID from other causes of hypogammaglobulinemia and to early detect monoclonal lymphoproliferation occurring over years. Moreover, since the sFLC pattern seems to be related to disease phenotypes and clinical manifestations of CVID and after confirmation by further studies, sFLC assay might be considered a promising prognostic tool for identifying patients at higher risk of developing enteropathy and chronic lung damage or splenomegaly. This will allow designing a tailored follow-up for CVID patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Serum free light chain assay is used in the diagnosis and monitoring of monoclonal gammopathic manifestations. For the kappa (κ)/lambda (λ) ratio, there is a 36% false-positive rate in patients without monoclonal gammopathic manifestations and a 30% false-negative rate in patients with monoclonal gammopathic manifestations. This study was undertaken to address the higher false-negative rate in λ chain–associated monoclonal lesions. Methods Results of serum protein electrophoresis, serum immunofixation electrophoresis, and serum free light chain assays were reviewed retrospectively. The results for serum free light chains in cases of intact immunoglobulin monoclonal gammopathic manifestations only were analyzed. Results Concentrations of involved serum free light chains were significantly higher in κ chain–associated lesions than in λ chain–associated lesions. The concentration of uninvolved light chains was significantly higher in λ chain–associated lesions. Conclusions κ light chains are present in significantly greater abundance than are λ chains in their respective monoclonal lesions. Moreover, κ and λ light-chain levels are not comparable for similar quantitative levels of monoclonal immunoglobulins. The findings warrant a reconsideration of the role of serum free light chain concentrations and involved to uninvolved serum free light chain ratio in designation of myeloma-defining conditions and other diagnostic criteria based on serum free light chain assay. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Concentration of serum free light chains has been promoted as an assay in the evaluation of monoclonal gammopathic manifestations. A high false-positive rate in patients without monoclonal gammopathic manifestations and a high false-negative rate in patients with those manifestations have been reported. The false-negative rate for lambda chain–associated lesions is higher than that for kappa chain–associated lesions. Objective To assess the serum free light chains in light-chain myelomas. Methods Concentrations of involved and uninvolved serum free light chains were retrospectively reviewed in patients with light-chain myelomas. Results The highest recorded levels of involved light chains in kappa-chain myelomas and lambda-chain myelomas were comparable. The levels of uninvolved light chains were higher, although not statistically significantly, in lambda-chain lesions. Conclusions The results of serum free light chains in light-chain myelomas support the clinical usefulness of the assay in monitoring patients with light chain myeloma. [ABSTRACT FROM AUTHOR]

To summarize distinct clinical characteristics and prognoses associated with and validate the novel hematologic response criteria in Chinese light-chain amyloidosis patients with a difference between involved and uninvolved free light chain (dFLC) < 50 mg/L. We retrospectively compared clinical features and outcomes between patients in the dFLC < 50 mg/L group (n = 74) and the ≥ 50 mg/L group (n = 248). Patients with dFLC < 50 mg/L presented less frequent and less severe cardiac involvement, but higher renal involvement. Additionally, more patients in the dFLC < 50 mg/L group showed intact immunoglobulin monoclonal protein and high immunoglobulin monoclonal protein levels. Moreover, patients in the dFLC < 50 mg/L group had significantly superior progression-free survival (PFS; not reached vs. 16.0 months; p < 0.001) and overall survival (OS; not reached vs. 41.0 months; p < 0.001) as compared with those in the dFLC ≥ 50 mg/L group. Furthermore, we confirmed that achieving complete response (CR) or low dFLC partial response (PR) predicted better OS in patients with initial dFLC ≥ 20 mg/L (not reached vs. 19 months; p = 0.005). Patients with initial dFLC < 50 mg/L represented distinct clinical manifestations and outcomes. Achieving CR or low dFLC PR might represent potential therapy goals allowing better survival and organ response in patients with dFLC between 20 and 50 mg/L. [ABSTRACT FROM AUTHOR]

Abstract Background Serum kappa and lambda free light chains (FLC) are useful in the diagnosis, prognosis and monitoring of patients with monoclonal gammopathies. The Binding Site and Siemens were the only suppliers of kits for these analyses until recently, when Sebia introduced an enzyme-linked immunosorbent assay (ELISA) on an automated instrument, DAS AP22 ELITE. Method Samples from routine analysis, controls and chronic kidney disease (CKD) patients were tested using the automated version of Sebia FLC ELISA with the AP22 ELITE and results were compared with Freelite on the SPA PLUS (The Binding Site). Results Sebia FLC ELISA showed a good performance using the AP22 ELITE. A concordance of 82% was found with the results obtained with Freelite. Sebia FLC is a reproducible assay, requiring less retesting than Freelite thanks to a broader range. Earlier findings that the results obtained are closer to the FLC monoclonal band measured by electrophoresis were confirmed. Higher kappa and lambda values obtained in CKD individuals were also shown, confirming that a kappa/lambda FLC ratio should be introduced by Sebia for CKD patients, as with The Binding Site. Conclusions Sebia put forward new technology that automatically measures free light chains. This technique is suitable for routine use; however, the results cannot be used interchangeably with Freelite kits. Highlights • Evaluation of Sebia FLC kits using the DAS AP22 ELITE, an ELISA processor. • Concordance between Freelite and Sebia FLC but no interchangeability of results. • Sebia FLC requires less retesting than Freelite. • Sebia FLC results are closer (around a 1.3-fold increase) to peak estimation by electrophoresis than Freelite. • K/L FLC ratio should be introduced by Sebia for CKD patients. [ABSTRACT FROM AUTHOR]

Background Serum free light chain (FLC) immunoglobulins are key biomarkers that aid in the diagnosis, prognosis and assessment of treatment response in patients with plasma cell disorders (PCD). Here we investigated the transference of manufacturer's reported κFLC, λFLC and κ to λ FLC reference intervals (RI) and established de novo FLC RI and diagnostic ranges on four instruments at three academic medical centers. In addition, we also compared the classification of patient FLC results using manufacturer's versus established RIs and diagnostic ranges. Methods CLSI EP28-A3C protocol was applied to investigate transference and establishment of FLC reference intervals on the cobas (Roche), Immage (Beckman), Optilite and SPA Plus (Binding Site). Serum κ FLC and λ FLC were measured in reference sera (N = 126) with estimation of central 95% RIs and FLC ratio diagnostic range (total range). Frequencies (%) in patient FLC results (N > 380 per institution) classified above, below or within manufacturer's versus established FLC RI were compared. Results Three of four instrument platforms did not exhibit acceptable transference of manufacturer's reported κ FLC RI. The manufacturer's reported FLC total diagnostic range did not encompass all values observed in reference sera for any of the four platforms evaluated. Established FLC ratio diagnostic ranges reduced the frequency of patient results classified above range for three of four platforms evaluated. Conclusions Transference of manufacturer's reported FLC RIs may be inappropriate for select instrument platforms. De novo establishment of FLC RIs specific to instrument platform is highly recommended in order to assure correct patient result classification. [ABSTRACT FROM AUTHOR]

Protein and immunofixation electrophoresis are the laboratory backbone assays for testing multiple myeloma (MM) and related plasma cell proliferative diseases. The secreted monoclonal proteins act as serological tumor markers, and the electrophoretic assays identify monoclonal proteins for diagnosis as well as quantitate these markers for monitoring clinical course and response to therapy. However these techniques present limitations, especially in patients with nonsecretory MM, light chain MM, and amyloid light chain amyloidosis. Freelite, a nephelometric/turbidimetric serum assay for the measurement of serum free light chains, has improved the management of patients with monoclonal gammopathies and has been included in international myeloma working group guidelines for the screening, prognostic, monitoring and as response criteria. Recently, a new assay, Hevylite; , was also approved by Food and Drug Administration for the monitoring of IgA and IgG MM. It allows the quantification of each immunoglobulin subtype (i.e., IgGκ, IgGλ, IgAκ, IgAλ), enables analysis of specific involved/monoclonal and uninvolved/polyclonal immunoglobulins heavy/light chain pairs, which produce immunoglobulin heavy/light chain ratios and may improve sensitivity for identifying residual disease and relapse in some patients. Together, these assays are important tools which will help us to achieve the correct diagnostic and follow-up of B cell dyscrasias.

Abstract Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) are included in the 2003 guidelines by the International Myeloma Working Group (IMWG). An updated version was then published in 2014, highlighting the importance of serum free light chain (sFLC) detection, as well as the κ/λ ratio as excellent indicators of clonality. At present, two commercial assays for sFLC quantification are available: the Freelite™ assay and the N-Latex assay. The first was developed by The Binding Site based on a mixture of polyclonal antibodies directed against a variety of FLC epitopes. It may be run on a wide range of nephelometers, as well as on turbidimeters. The second method was developed by Siemens and runs exclusively on Siemens instruments. It employs a probe mixture of mouse monoclonal antibodies. The aim of our study was to evaluate sFLC measurement and calculated κ/λ ratio in 85 patients with monoclonal gammopathies (MGs) in order to compare methods. We demonstrated that there is only a moderate concordance between the two FLC assays. In particular, in one case, we observed no qualitative alterations of the serum protein pattern, and in the absence of a Freelite™ assay, sFLC measurement would not have been possible to highlight the increase of λ FLC. [ABSTRACT FROM AUTHOR]

The serum immunoglobulin free light chain assay measures levels of free k and l immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly two- thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.

For many years, Bence Jones proteinuria has been an important diagnostic marker for multiple myeloma. Relatively new serum tests for free kappa and free lambda light chains of immunoglobulins reflect the production of free light chains more accurately than urine tests. In this study, we examined the value of serum free light chains measurement in the diagnosis of some neoplastic diseases and the discrepance between the findings of serum protein electrophoresis and serum free light chains. Thirty one patients (f=19, m=12) were included in the study, most of them with blood malignant diseases. The results show that in six patients with normal gamma and beta electrophoresis fractions there are abnormal levels of free light chains and/or an abnormal k/l ratio. In 20 patients we found an abnormal k/l ratio, and in 21 patients we found an abnormal k or l level, or both. The obtained results show the important role of serum free light chains determination in identifying patients with monoclonal gammopathies.

Introduction: There are two commercially available tests for measurement of serum free light chains (sFLC) in multiple myeloma (MM) patients - Freelite and N Latex FLC. The aim of this study was to perform an assessment and direct comparison of the usefulness of the methods in routine clinical practice. Methods: 40 refractory/relapsed MM patients underwent routine disease activity assessment studies, along with sFLC analysis using both assays. Correlation and concordance between the tests and sensitivity of studied methods of sFLC assessment were established. Special attention was focused on sFLC results in patients finally evaluated after completing the treatment. Results: A weak correlation for the measurement of both κ [Passing-Bablok slope (PB) = 0.7681] and λ chains [(PB) = 1.542] was found. Using Bland-Altman plots, a bias of 0.0467 (κ) and -0.2133 (λ) between the measurements was documented. The concordance coefficient equaled 0.87 for κ, 0.62 for λ and 0.52 for κ/λ ratio. Ten patients had an abnormal Freelite assay κ/λ ratio and normal N Latex FLC κ/λ ratio. Three of these patients had negative serum protein electrophoresis results and fulfilled diagnostic criteria of stringent complete remission (sCR) according to N Latex FLC (but not according to Freelite). When the κ/λ ratio obtained by both methods was compared to patients' serum/urine protein electrophoresis and immunofixation results, sensitivity of Freelite and N Latex FLC was established to be 62.5% and 41%, respectively. Conclusions: There was no strong correlation or concordance between the two assays, and the sensitivity in terms of sFLC detection was different. This may cause problems when diagnosis of sCR is considered. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is characterized by heterogeneous clinical behavior and there is a need for improved biomarkers. The current study evaluated the prognostic significance of serum free light chains (sFLC, kappa, and lambda) and other serum markers (bar, serum thymidine kinase (sTK), soluble CD23, and LDH) together with established biomarkers in 289 patients enrolled into the LRF CLL4 trial. In a multivariable analysis of serum markers alone, higher big and kappa light chains were statistically significant in predicting disease progression and higher blg, and sTK in predicting mortality. In multivariable analysis for overall survival the following were independently significant: β2M levels, immunoglobulin gene (IGHV) mutational status (>98% homology), age, 17p13 deletions (>10%), and CD38 expression. β2M is the only serum marker that retained clear independent value as a biomarker in the LRF CLL4 trial and remains powerfully prognostic requiring evaluation in any future method of risk stratifying patients. [ABSTRACT FROM AUTHOR]

Response to treatment in patients with a plasma cell disorder is typically measured by evaluating the bone marrow and myeloma markers, including monoclonal protein spike and immunofixation ( IFE) in blood and urine, and serum free light chains ( sFLCs). Stringent complete response criteria for Multiple Myeloma ( MM) patients require a normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. We performed a retrospective chart review to further evaluate these criteria. A total of 142 patient charts were analysed. Of these, 17 patients were found to have an abnormal sFLC ratio, but no other evidence of disease, including normal flow cytometry and normal fluorescence in situ hybridization ( FISH) analysis on highly selected plasma cells. In all patients, the abnormal sFLC ratio was caused by abnormalities in the serum kappa light chains. These results suggest that current definitions may need to be revised to take aberrancies related to abnormal immune recovery into account. [ABSTRACT FROM AUTHOR]

Objectives: Serum free light chain assay is a recommended screening test for monoclonal gammopathies. Anecdotal observations indicated a high rate of false-positive abnormal κ/λ ratios. This study was undertaken to ascertain the magnitude of the false-positive rate and factors contributing to the error rate.Methods: Results of serum protein electrophoresis, serum free light chains, and related tests, usually done for investigation of suspected monoclonal gammopathy, were reviewed retrospectively for 270 patients and 297 observations.Results: Using the conventional κ/λ ratio, 36.4% of the ratios were abnormal, in the absence of monoclonal gammopathy. When the renal κ/λ ratio was used, the rate of abnormal κ/λ ratios was 30.1%. In patients with a γ-globulin concentration of 1.6 g/dL or more, the usual κ/λ ratio was abnormal in 54.8% of the patients. Urine protein electrophoresis was used in 53 (19.6%) instances, whereas bone marrow examination was done in 65 (24.1%) cases.Conclusions: Usual κ/λ ratio was abnormal in 36.4% of the observations in patients without evidence of monoclonal gammopathy, and an abnormal κ/λ ratio should not be used as the sole indicator for diagnosis of neoplastic proliferation of the lympho-plasmacytic system. Hypergammaglobulinemia is associated with a higher rate of false-positive abnormal κ/λ ratios. Examination of urine for monoclonal immunoglobulins may be underused, and recommendations by some to use serum free light chain assay in place of, rather than as an adjunct to, urine electrophoresis are not warranted. [ABSTRACT FROM AUTHOR]

The measurement of monoclonal protein ( M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β- and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/ light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins. [ABSTRACT FROM AUTHOR]

Résumé La maladie des dépôts d’immunoglobulines monoclonales (MIDD) est une complication rare des proliférations plasmocytaires monoclonales, définie par des dépôts linéaires rouge Congo négatifs, de chaînes légères (LCDD), lourdes (HCDD), ou les 2 (LHCDD), le long des membranes basales. L’atteinte rénale est quasi constante. Le diagnostic doit être évoqué devant un syndrome glomérulaire chez un patient porteur d’une gammapathie monoclonale, mais l’absence de l’un de ces 2 critères n’exclut pas le diagnostic. De plus, tous les patients (y compris HCDD) atteints de MIDD présentent une anomalie du rapport κ/λ sérique, justifiant leur dosage devant toute insuffisance rénale inexpliquée chez le patient âgé de plus de 50 ans. La stratégie thérapeutique incluant des schémas à base d’inhibiteur du protéasome (bortézomib) paraît efficace et bien tolérée, avec une augmentation de la survie rénale et globale par rapport aux séries historiques, lorsque le traitement est introduit avant le stade d’insuffisance rénale chronique évoluée, justifiant l’intérêt du diagnostic précoce de la maladie. Chez des patients sélectionnés, le traitement intensif avec autogreffe de cellules souches hématopoïétiques est à discuter en seconde ligne. L’obtention d’une réponse hématologique, évaluée sur la différence entre la chaîne légère libre impliquée et la non impliquée (dFLC) représente l’enjeu de la prise en charge thérapeutique. Une valeur de dFLC de moins de 40 mg/L, en fin de traitement est un facteur prédictif indépendant du pronostic rénal et vital au cours des MIDD. Monoclonal immunoglobulin (Ig) deposition disease (MIDD) is a rare complication of plasma cell disorders, defined by linear Congo red-negative deposits of monoclonal light chain (LCDD), heavy chain (HCDD) or both (LHCDD) along basement membranes. MIDD should be suspected in patients presenting with glomerular proteinuria and monoclonal gammopathy, but none of these criteria is necessary for the diagnosis although renal involvement is prominent. Since an abnormal serum κ/λ ratio is found in virtually all MIDD patients, including those with HCDD, serum free light chain assay should be included in the initial workup in patients older than 50 presenting with kidney disease. Bortezomib-based regimens are efficient and well tolerated, resulting in improvement in both renal and global survival, comparatively to historical series. High dose melphalan with autologous stem cell transplantation may be proposed as second line therapy in selected patients. The achievement of hematological response, based on the difference between involved and uninvolved serum free light chains (dFLC), is mandatory. In a recent series, post-treatment dFLC < 40 mg/L was the major predictive factor of renal response and was associated with improvement of both renal and global survival. In MIDD, bortezomib-based therapy is safe and efficient when introduced early after diagnosis. dFLC response is a favorable prognostic factor for renal survival. [ABSTRACT FROM AUTHOR]

The objective was to explore the relationship between the levels of serum and urinary free light chains (FLCs) during the progression of renal damage in multiple myeloma (MM) patients. We examined 91 cases of MM patients, detected levels of serum FLCs (sFLCs), urinary FLCs (uFLCs), and serum creatinine at the same time, and then compared sFLC and uFLC levels during normal and abnormal serum creatinine phases. Among the 91 MM patients, 22 patients had abnormal serum creatinine levels (no uremia), and 69 patients had normal serum creatinine levels. The levels of sFLCs and uFLCs in patients with abnormal serum creatinine were beyond normal, namely both serum and urine positive (serum+ and urine+), and the average concentrations of κFLCs and λFLCs were 516.76 and 604.67 mg/L, respectively. Of the 69 patients with normal creatinine levels, there were 39 and 30 cases of κ-type and λ-type MM, respectively. Of the κ-type patients, 11 cases were serum positive and urine negative (serum+ and urine−) with an average concentration of 55.47 mg/L, and 28 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 513.09 mg/L. Of the λ-type patients, 16 cases were serum positive and urine negative (serum+ and urine−) with an average concentration of 78.44 mg/L, and 14 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 518.08 mg/L. The levels of uFLCs did not parallel those of sFLCs. In addition to sFLC levels, renal function affected uFLC concentrations. As MM progressed, the concentration of sFLCs increased in a step-by-step manner, and the uFLCs changed from negative to positive to negative again. Therefore, the whole progression included three phases: sserum+ and urine−, serum+ and urine+, and then serum+ and urine−. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the authors discuss the impact of exercise on the variation of serum free light chains.

Introduction Serum concentrations of polyclonal free light chains ( FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein ( CRP), in chronic and acute disease. Methods We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease ( CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. Results There was a weak association between polyclonal FLC and high-sensitivity CRP (hs- CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. Conclusion Polyclonal FLC and hs- CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs- CRP and polyclonal FLC in combination for risk stratification in disease populations. [ABSTRACT FROM AUTHOR]

Objectives: To determine the most clinically effective diagnostic testing strategy for plasma cell disorders in the clinical laboratory. Methods: Serum and urine samples from 2,799 patients with suspected plasma cell dyscrasias were tested by alternative diagnostic testing strategies consisting of serum protein electrophoresis (SPE) with either urine protein electrophoresis (UPE) or serum free light chain (sFLC) analysis. Results: The combination of sFLC analysis and SPE had the greatest sensitivity (100%), detecting abnormalities in all 124 patients diagnosed with plasma cell disorders. Routine sFLC testing would have had much potential health benefit for two patients in the study population. First, a patient who had a markedly abnormal sFLC result was diagnosed with light chain deposition disease by renal biopsy, but no abnormality was detected by SPE or UPE. Second, a patient diagnosed with multiple plasmacytomas following biopsy of a lung tumor had a grossly abnormal sFLC result but an equivocal weak-positive SPE result, and no urine sample was received by the laboratory for the patient. Conclusions: Our study suggests that the combination of SPE and sFLC analysis is the most clinically effective first-line diagnostic testing strategy for detecting plasma cell disorders in the clinical laboratory. [ABSTRACT FROM AUTHOR]