An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.

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.

The kappa/lambda ratio of surface immunoglobulin light chain as a valuable parameter for MRD assessment in CLL with atypical immunophenotype.

In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10-4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10-4. We propose this method as an effective MRD assay.

Catalase Activity of IgG and κκ-IgG, λλ-IgG, and κλ-IgG Subfractions in HIV-Infected Patients and Healthy Donors.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors. METHODS: Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition. RESULTS: The relative catalase activity of antibodies from HIV-infected patients (kcat = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher (p = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1). CONCLUSIONS: Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.

A rare case of IgA lambda multiple myeloma in a 32-year-old woman with t(14;16) translocation associated with kidney injury and non-albumin proteinuria.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder characterized by monoclonal differentiated plasma cells. While it is more commonly diagnosed in elderly individuals, it can also affect younger populations, though with a lower incidence. CASE PRESENTATION: Here, we present the case of a 32-year-old woman diagnosed with IgA lambda MM. She presented with fatigue, nausea, acute kidney injury (AKI) with a rapid increase in creatinine, and anemia. A kidney biopsy was done to rule out a rapidly progressive glomerular disease and a diagnosis was thus reached. A genetic workup revealed t(14;16) translocation and an extra copy of TP53. The patient received aggressive intravenous steroids and intravenous fluid resuscitation, resulting in an improvement in renal function. Treatment with daratumumab in combination with bortezomib, thalidomide, and dexamethasone was initiated and well tolerated. Despite the generally poor prognosis of IgA MM, our case emphasizes the importance of considering MM in young patients with unexplained kidney injury. CONCLUSION: Early recognition and prompt intervention are essential in managing MM patients, especially in those with high-risk cytogenetic abnormalities. This case serves as a reminder for clinicians to maintain a high index of suspicion for MM, even in younger populations, when presented with unexplained kidney injury.

A case report of biclonal immunoglobulin D lambda/lambda multiple myeloma in patient with liver echinococcosis.

Less than 2% of all symptomatic multiple myeloma (MM) has immunoglobulin D (IgD) as monoclonal protein. Biclonal gammopathy is much rarer. At the time of diagnosis, disease is often in advanced stage, including renal failure, anemia, hypercalcemia and lytic bone lesions. Due to the rarity of myeloma itself, but also due to the fact that anti-IgD antisera is not used in routine practice, there are only a few reports of IgD MM described in the literature. This case report describes a patient with IgD lambda MM with anemia and renal failure. Anemia, renal failure, and > 80 percent plasma cells in bone biopsy in our patient with IgD lambda MM meets International Myeloma Working Group criteria for diagnosis of MM. The patient clinical course was similar to other patients with IgD MM. The final result of serum protein immunofixation (s-IFE) showed IgD lambda and free lambda monoclonal bands. To prevent misdiagnosis, it is necessary to use anti-IgD and anti-IgE antisera whenever the serum protein immunofixation with IgA, IgM, IgG, kappa and lambda antiserums shows a kappa or lambda monoclonal band without monoclonal band in heavy chain.

Serum free light chains among twin siblings: is the kappa/lambda ratio genetically determined?

BACKGROUND: Serum kappa, lambda, the K/λ light chain concentrations are used for screening, diagnosis, and monitoring of patients with multiple myeloma and other plasma cell disorders. Biological variation studies conducted on healthy subjects showed that free light chains have a low within and high between-individual variation. We determined if this variation were genetically linked. METHODS: We obtained a single serum sample from 16 pairs of identical twins, 8 neonate twins, and 19 presumed directly-related siblings children, measured Κ and λ light chains and computed the Κ/λ ratio. RESULTS: As expected, Κ/λ results from each twin neonate were near identical (reflecting maternal/placental transfer). For older children and adult twins, the Κ/λ ratio form a cluster of results that were a subset of the reference range. There was one outlier, a female with a high, different from her twin sister. She likely had a monoclonal gammopathy (no followup was possible). Excluding this pair, results from neonate twins (14.4% ±10.3%) and non-neonate twins (18.0 ± 15.3%) were not significantly different. Results between non-twin siblings were more scattered (53.2%±53.4%) and different from neonate and non-neonate twin adult and children. CONCLUSION: We suggest that the Κ/λ free light chains may be genetically linked.

Synchronous multiple myeloma and lung adenocarcinoma: A clinical series.

BACKGROUND: Multiple myeloma (MM) is characterised by an increased number of monoclonal immunoglobulin-producing plasma cells that malignantly grow in the bone marrow. Lung cancer is one of the most common malignancies and at the advanced stage may become metastatic to the bone. Rarely, MM and lung cancer are synchronously present in the same patient. RESULTS: In this report, we describe five cases of MM synchronous with lung adenocarcinoma including λ light chain in three cases and Ï° light chain in two cases. Two patients achieved complete remission, and no progression was seen in two patients. CONCLUSION: In conclusion, synchronous MM and lung adenocarcinoma are clinically rare, and diagnosis should be made scrupulously based on morphology, immunology, cytogenetics, molecular biology and biopsy pathology.

Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL). Bone marrow biopsy and PET/CT ruled out a systemic lymphoma. Extended history taking, blood and urine testing (including cardiac biomarkers) identified no evidence of systemic amyloidosis-induced organ dysfunction.Primary cerebral AL amyloidoma is a very rare entity where optimal treatment is difficult to assess. The patient was treated with locally applied volumetric modulated arc radiotherapy, 24 Gy, divided in 12 fractions. Afterwards, the paresis of the left arm partially resolved, and the function of the left leg improved. Seizures did not occur anymore.

Defect in Automated Antigen Excess Detection Discovered after Reviewing Serum Free Light Chain Results in Context with Clinical Findings.

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.

Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study.

OBJECTIVES: Diagnosis of light chain amyloidosis (AL) requires demonstration of amyloid deposits in a tissue biopsy followed by appropriate typing. Previous studies demonstrated increased dimerization of monoclonal serum free light chains (FLCs) as a pathological feature of AL. To further examine the pathogenicity of FLC, we aimed at testing amino acid sequence homology between circulating and deposited light chains (LCs). METHODS: Matched tissue biopsy and serum of 10 AL patients were subjected to tissue proteomic amyloid typing and nephelometric FLC assay, respectively. Serum FLC monomers (M) and dimers (D) were analyzed by Western blotting (WB) and mass spectrometry (MS). RESULTS: WB of serum FLCs showed predominance of either κ or λ type, in agreement with the nephelometric assay data. Abnormal FLC M-D patterns typical of AL amyloidosis were demonstrated in 8 AL-λ patients and in one of two AL-κ patients: increased levels of monoclonal FLC dimers, high D/M ratio values of involved FLCs, and high ratios of involved to uninvolved dimeric FLCs. MS of serum FLC dimers showed predominant constant domain sequences, in concordance with the tissue proteomic amyloid typing. Most importantly, variable domain sequence homology between circulating and deposited LC species was demonstrated, mainly in AL-λ cases. CONCLUSIONS: This is the first study to demonstrate homology between circulating FLCs and tissue-deposited LCs in AL-λ amyloidosis. The applied methodology can facilitate studying the pathogenicity of circulating FLC dimers in AL amyloidosis. The study also highlights the potential of FLC monomer and dimer analysis as a non-invasive screening tool for this disease.

Clinical specificity of two assays for immunoglobulin kappa and lambda free light chains.

OBJECTIVES: Free light chain (FLC) assays and the ratio of κ/λ are recommended for diagnosis, prognosis and monitoring of plasma cell dyscrasias (PCD). Limited data exists on FLC clinical specificity in patients diagnosed with other conditions. METHODS: We assessed the κ, λ, and κ/λ FLC ratio using the FreeLite assay and the Sebia FLC ELISA assay in 176 patients with clinical presentations of fatigue, anemia, polyclonal hypergammaglobulinemia, joint disorders, kidney disease and non PCD-cancers with no monoclonal protein observed on serum protein electrophoresis or MASS-FIX immunoglobulin isotyping. Manufacturer defined reference intervals (RI) and glomerular filtration rate (GFR) specific RI (renal RI) were utilized. RESULTS: For the κ/λ ratio, 68.7 % (121/176) of specimens on the FreeLite and 87.5 % (154/176) of specimens on the Sebia assay were within RI. For κ, 68.2 % (120/176) and 72.2 % (127/176) of results were outside RI for FreeLite and Sebia respectively. For λ, 37.5 % (66/176) and 84.1 % (148/176) of FreeLite and Sebia results were outside RI. With FreeLite and Sebia, patients with kidney disease (n=25) had the highest κ/λ ratios. 44 patients (25.0 %) had GFR <60 mL/min/BSA. When renal RI were applied, 13.6 % had a FLCr outside the renal RI with FreeLite, and 4.5 % with Sebia. CONCLUSIONS: In a cohort of patients with signs and symptoms suggestive of PCDs, but ultimately diagnosed with other conditions, Sebia FLC had improved clinical specificity relative to FreeLite, if one was using an abnormal κ/λ ratio as a surrogate for monoclonality.

Values of Immunoglobulin and Complements for Evaluating Treatment Outcomes of Patients with Multiple Myeloma.

BACKGROUND: The goal was to detect the levels of immunoglobulin (Ig) and complements (C) in patients newly diagnosed as multiple myeloma (MM) and to analyze their value in evaluating the efficacy of bortezomib and the impact on survival time. METHODS: A total of 125 patients newly diagnosed as MM admitted to our hospital were included into the research group, while another 118 healthy volunteers were recruited into the control group. The effectiveness of Ig and C in efficacy evaluation after treatment with bortezomib and the influencing factors for the survival rate were analyzed. Moreover, survival analysis was conducted. RESULTS: The response rate was 78.51% in the research group. The sensitivity and area under the curve (AUC) of combination of serum IgG, κ light chain, λ light chain, C3 and C4 levels in efficacy evaluation were 97.89% and 0.791, respectively, which were superior to those of any single indicator (p < 0.05). The proportion of stage III cases and the levels of serum IgG, κ light chain, λ light chain, C3 and C4 among the dead patients were higher than those among the surviving patients (p < 0.05). Stage III, serum IgG, κ light chain, λ light chain, C3 and C4 were all the risk factors for death in the research group. The increase in the above indicators was associated with the death of patients (p < 0.05). CONCLUSIONS: The combination of serum IgG, κ light chain, λ light chain, C3 and C4 levels can be more effective than any single indicator in efficacy evaluation of bortezomib.

Functional analysis of tumor-derived immunoglobulin lambda and its interacting proteins in cervical cancer.

BACKGROUND: Immunoglobulin lambda (Igλ) has been reported to be expressed in many normal and tumor tissues and cells. However, the function and clinical significance of tumor-derived Igλ remain unclear. METHODS: The differential expressions of Immunoglobulin Lambda Constants (IGLCs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were examined with The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases. The effects of IGLCs on patient clinical phenotypes and prognosis were explored via bioinformatics analyses based on the TCGA databases. We used the bioinformatics analyses based on the TCGA and GTEx databases to elucidate the correlations among IGLC expressions, immunomodulator expressions, tumor stemness, and infiltration scores of tumor infiltrating immune cells. Co-immunoprecipitation (Co-IP) and silver staining combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to obtain potential tumor-derived Igλ-interacting proteins. Functional annotation of candidate proteins identified by LC-MS/MS was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The bioinformatics analyses of 7 IGLCs in CESC and normal cervical tissues were performed based on TCGA, GTEx, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Protein-protein interaction (PPI) network was analyzed based on tumor-derived Igλ-interacting proteins in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Immunohistochemistry (IHC) was used to validate the expressions of IGLCs in CESC. RESULTS: We found that the expressions of the majority of IGLCs (IGLC1, IGLC2, IGLC3, IGLC4, IGLC5, IGLC6, and IGLC7) were upregulated in CESC tissues, compared with those in normal cervical tissues. The expressions of IGLC5 and IGLC7 had significant difference in different pathologic metastasis (M), one of tumor, node, and metastasis (TNM) staging system, categories of CESC. Except for disease-free interval (DFI), 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC7) expression levels were positively associated with patient overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) respectively in CESC tissues. 5 IGLC (IGLC1, IGLC2, IGLC3, IGLC6, and IGLC7) expressions were positively correlated with the expressions of a majority of immunomodulators respectively in CESC tissues. Tumor stemness was negatively correlated with the expressions of 4 IGLCs (IGLC1, IGLC2, IGLC3, and IGLC7) respectively in CESC tissues. Except for IGLC4, IGLC5, and IGLC7, 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC6) expressions were positively correlated with infiltration scores of 6 tumor-infiltrating immune cells (B cell, T cell CD4, T cell CD8, neutrophil, macrophage, and DC). After analyses of the above bioinformatics data of tumor-derived Igλ, Co-IP and LC-MS/MS were used to confirm that 4 proteins (RPL7, RPS3, H1-5, and H1-6) might interact with tumor-derived Igλ in cervical cancer cells. Functional analyses of these candidate proteins showed that they interacted with many proteins and were involved in various cellular biological processes. Finally, IHC was used to further confirm the above bioinformatics results, it was indicated that the expression level of Igλ in cervical adenocarcinoma and cervical squamous cell carcinoma was higher than that in normal cervical tissue. CONCLUSION: This study comprehensively investigated the functions of tumor-derived Igλ and its interacting proteins based on bioinformatics analysis and the potential value of Igλ as a prognostic and therapeutic marker for CESC, providing new direction and evidence for CESC therapy.

Investigation of the Diagnostic Value of sFLC and Other Indicators in the Detection of M Protein in LCMM.

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.

Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.

Transcription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3' Igλ domain, Eλ3-1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and antisense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3-1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.

Quantification of Free Immunoglobulin Light Chains in Urine.

BACKGROUND: The serum-free immunoglobulin light chain assay has been recommended as a screening test for monoclonal gammopathy. We evaluated the usefulness of urine free immunoglobulin light concentration for selection of specimens for immunofixation electrophoresis. METHODS: Using kits from The Binding Site for Freelite ®, we validated examination of urine for measuring free κ and λ light chains. The results of urine free light chain concentrations were evaluated to ascertain if the results could be used to reduce the number of specimens requiring urine protein immunofixation electrophoresis. RESULTS: In the 515 specimens examined, there was no evidence of monoclonal gammopathy or history of monoclonal gammopathy in 331. Monoclonal κ or λ light chains were detectable in 42 and 30 specimens, respectively. There was history of κ or λ chain associated monoclonal gammopathy in 62 and 50 patients, respectively. In the 38 monoclonal κ positive urine specimens, with light chain data, κ/λ ratio was >5.83 in all specimens. In 27 specimens positive for monoclonal λ light chains, with light chain data, the urine λ/κ ratio was > 0.17 in 24 of 27 specimens and > 0.041 in all specimens. In patients without monoclonal gammopathy all specimens had a κ/λ ratio of >5.83 or λ/κ ratio >0.17. CONCLUSIONS: The Freelite ® assay from The Binding Site is suitable for quantification of free light chains in urine. In patients with known history of monoclonal gammopathy, urine immunofixation electrophoresis may be omitted in specimens with κ/λ ratio of <5.83 for κ associated lesions and λ/κ ratio of <0.041 for λ associated lesions. However, the results do not support using this test for first-time urine testing for monoclonal light chains as it is not predictive of positive result, nor does it exclude a monoclonal light chain in urine.

Reference Intervals for Plasma Free Kappa and Lambda Chains and Kappa/Lambda Ratio using PENIA.

BACKGROUND: Determination of free light chains is used increasingly for patients with multiple myeloma and other plasma cell dyscrasias. The aim of the present study was to define reference intervals for free kappa and lambda chains and kappa/lambda ratio in lithium heparin plasma and compare the test results with cystatin C based estimated glomerular filtration rate. METHODS: Free kappa and lambda chains were measured in Liheparin plasma from 222 healthy blood donors using free light chain reagents and a BNII nephelometer from Siemens Diagnostics. RESULTS: Calculated reference intervals for kappa chain, free was 4.73 mg/L (90% confidence interval 4.00 - 5.45) - 22.66 mg/L (20.33 - 24.98), for lambda chain, free was 4.33 mg/L (3.70 - 4.95) - 29.28 mg/L (26.96 - 31.59), and for Kappa/Lambda Chain ratio 0.59 (0.56 - 0.62) - 1.46 (1.37 - 1.56). There was no need for gender or age specific reference intervals. Cystatin C based estimated glomerular filtration rate had a significant effect on the levels of free light chains. CONCLUSIONS: The study presents reference intervals for plasma free light chains and compared results of estimated glomerular filtration rate with free light chains of kappa and lambda.