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.

Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis.

Background: Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate. Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods. Methods: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). Conclusions: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.

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.

Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index.

The diagnosis of MS relies on a combination of imaging, clinical examinations, and biological analyses, including blood and cerebrospinal fluid (CSF) assessments. G-Oligoclonal bands (OCBs) are considered a "gold standard" for MS diagnosis due to their high sensitivity and specificity. Recent advancements have involved the introduced of kappa free light chain (k-FLC) assay into cerebrospinal fluid (CSF) and serum (S), along with the albumin quotient, leading to the development of a novel biomarker known as the "K-index" or "k-FLC index". The use of the K-index has been recommended to decrease costs, increase laboratory efficiency, and to skip potential subjective operator-dependent risk that could happen during the identification of OCBs profiles. This review aims to provide a comprehensive overview and analysis of recent scientific articles, focusing on updated methods for MS diagnosis with an emphasis on the utility of the K-index. Numerous studies indicate that the K-index demonstrates high sensitivity and specificity, often comparable to or surpassing the diagnostic accuracy of OCBs evaluation. The integration of the measure of the K-index with OCBs assessment emerges as a more precise method for MS diagnosis. This combined approach not only enhances diagnostic accuracy, but also offers a more efficient and cost-effective alternative.

Molecular basis for differential Igk versus Igh V(D)J joining mechanisms.

In developing B cells, V(D)J recombination assembles exons encoding IgH and Igκ variable regions from hundreds of gene segments clustered across Igh and Igk loci. V, D and J gene segments are flanked by conserved recombination signal sequences (RSSs) that target RAG endonuclease1. RAG orchestrates Igh V(D)J recombination upon capturing a JH-RSS within the JH-RSS-based recombination centre1-3 (RC). JH-RSS orientation programmes RAG to scan upstream D- and VH-containing chromatin that is presented in a linear manner by cohesin-mediated loop extrusion4-7. During Igh scanning, RAG robustly utilizes only D-RSSs or VH-RSSs in convergent (deletional) orientation with JH-RSSs4-7. However, for Vκ-to-Jκ joining, RAG utilizes Vκ-RSSs from deletional- and inversional-oriented clusters8, inconsistent with linear scanning2. Here we characterize the Vκ-to-Jκ joining mechanism. Igk undergoes robust primary and secondary rearrangements9,10, which confounds scanning assays. We therefore engineered cells to undergo only primary Vκ-to-Jκ rearrangements and found that RAG scanning from the primary Jκ-RC terminates just 8 kb upstream within the CTCF-site-based Sis element11. Whereas Sis and the Jκ-RC barely interacted with the Vκ locus, the CTCF-site-based Cer element12 4 kb upstream of Sis interacted with various loop extrusion impediments across the locus. Similar to VH locus inversion7, DJH inversion abrogated VH-to-DJH joining; yet Vκ locus or Jκ inversion allowed robust Vκ-to-Jκ joining. Together, these experiments implicated loop extrusion in bringing Vκ segments near Cer for short-range diffusion-mediated capture by RC-based RAG. To identify key mechanistic elements for diffusional V(D)J recombination in Igk versus Igh, we assayed Vκ-to-JH and D-to-Jκ rearrangements in hybrid Igh-Igk loci generated by targeted chromosomal translocations, and pinpointed remarkably strong Vκ and Jκ RSSs. Indeed, RSS replacements in hybrid or normal Igk and Igh loci confirmed the ability of Igk-RSSs to promote robust diffusional joining compared with Igh-RSSs. We propose that Igk evolved strong RSSs to mediate diffusional Vκ-to-Jκ joining, whereas Igh evolved weaker RSSs requisite for modulating VH joining by RAG-scanning impediments.

Affinity purification of mAb from serum-containing hybridoma culture supernatant through a novel nanobody that discriminates mouse IgG from bovine IgG by recognizing the mouse kappa constant region (mCK).

When purifying mAb from serum-containing hybridoma culture supernatant, it is essential that mouse IgG remains free from contaminations of bovine IgG. However, the broadly used Protein A resin cannot achieve this goal due to binding between both mouse and bovine IgG. Here, a novel nanobody-based affinity purification magnetic beads that discriminates mouse IgG from bovine IgG was developed. To bind all subtypes of mouse IgG (IgG1, IgG2a, IgG2b and IgG3) that contain the kappa light chain, mCK (mouse kappa constant region)-specific nanobody binders were selected from an immune phage display VHH library; this library was constructed with peripheral blood mononuclear cells (PBMCs), which were collected from Bactrian camels immunized with a mix of intact mouse IgGs (IgG1, IgG2a, IgG2b and IgG3). A novel clone that exhibited a higher expression level and a higher binding affinity was selected (4E6). Then, the 4E6 nanobody in the format of VHH-hFC (human Fc) was conjugated on magnetic beads with a maximal binding capacity of 15.41±0.69 mg mouse IgG/mL beads. Furthermore, no bovine IgG could be copurified from hybridoma culture supernatant with immunomagnetic beads. This approach is valuable for the large-scale in vitro production of highly pure antibodies by hybridoma cells.

Light chain deposition disease presenting with gastrointestinal disorder as primary manifestation: report of two cases and literature review.

Light chain deposition disease (LCDD) is an under-recognized condition characterized by deposition of abnormal monoclonal light chains in tissues, leading to organ dysfunction. LCDD involving the gastrointestinal tract is very uncommon, and its diagnosis is challenging. We herein report two cases of LCDD that manifested as inflammatory bowel disease-like symptoms and protein-losing gastroenteropathy. Both patients were women in their early 60s. Tissue biopsies from the gastrointestinal mucosa demonstrated extracellular deposits, which were negative by Congo red staining but positive for κ-light chain by immunohistochemistry. The recent literature on LCDD was reviewed. When patients unexpectedly show extracellular deposits in gastrointestinal biopsy specimens, evaluation of immunoglobulin chains is recommended for diagnosis of LCDD after systemic amyloidosis has been excluded.

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.

Sequence diversity of kappa light chains from patients with AL amyloidosis and multiple myeloma.

BACKGROUND: AL amyloidosis (AL) results from the misfolding of immunoglobulin light chains (IG LCs). Aim of this study was to comprehensively analyse kappa LC sequences from AL patients in comparison with multiple myeloma (MM). OBJECTIVE: We analysed IGKV/IGKJ usage and associated organ tropism and IGKV1/D-33 in terms of mutational analysis and theoretical biochemical properties. MATERIAL AND METHODS: cDNA and bulk RNA sequencing of the LCs of AL and MM patients. RESULTS: We studied 41 AL and 83 MM patients showing that IGKV1 was most expressed among kappa AL and MM, with higher frequency in AL (80% vs. 53%, p = .002). IGKV3 was underrepresented in AL (10% vs. 30%, p = .014). IGKJ2 was more commonly used in AL than in MM (39% vs. 29%). Patients with IGKV1/D-33 were associated with heart involvement (75%, p = .024). IGKV1/D-33-segments of AL had a higher mutation count (AL = 12.0 vs. MM = 10.0). FR3 and CDR3 were most frequently mutated in both, with a median mutation count in FR3 being the highest (AL = 4.0; MM = 3.5) and one mutation hotspot (FR3 (83I)) for IGKV1/D-33/IGKJ2 was associated with cardiac involvement. CONCLUSION: This study confirmed that germline usage has an influence on AL amyloidosis risk and organ involvement.

A comparison of measles-rubella-zoster reaction, oligoclonal IgG bands, oligoclonal kappa free light chains and kappa index in multiple sclerosis.

BACKGROUND AND OBJECTIVES: To evaluate the diagnostic performance of the measles-rubella-zoster reaction (MRZR) in a large real-world multiple sclerosis (MS) cohort. Second, to compare MRZR with the determination of oligoclonal IgG bands (OCB), oligoclonal kappa free light chain bands (oKFLC), and the KFLC index. METHODS: A single-center retrospective study was conducted at the University Hospital Ostrava (Czech Republic). Patients were eligible if aged ≥18 years with a determined clinical diagnosis. IgG antibodies against measles (M), rubella (R), and varicella zoster (Z) viruses were determined in paired CSF and serum using ELISA and MRZR indicated as positive if at least two components had an antibody index >1.4. OCB and oKFLC were detected by means of isoelectric focusing, and KFLC CSF and serum concentrations for calculation of the KFLC index were determined immunochemically. RESULTS: A total of 1,751 patients were included in the analyzed data set, which comprised 379 MS patients and 1,372 non-MS controls. The frequency of positive MRZR was higher in MS than in non-MS cases (MS 32.2 % vs non-MS 2.8 %; p < 0.001). This corresponded to a specificity of 97.2 % (95 % CI 96.1-98.0) and sensitivity of 32.2 % (95 % CI 27.5-37.2) and overall accuracy of 83.1 % (95 % CI 81.3-84.8). In comparison, the highest sensitivity of 95.6% (95 % CI 93.0-97.5) was for OCB with specificity of 86.9 % (95 % CI 84.9-88.7), followed by oKFLC with sensitivity and specificity of 94.7 % (95 % CI 91.5-96.9) and 78.4% (95 % CI 75.7-80.8), respectively, and the KFLC index with sensitivity of 92.5 % (95 % CI 86.6-96.3) and specificity of 93.5 % (95 % CI 90.5-95.9). DISCUSSION: MRZR remains a very specific test for the diagnosis of MS but has low sensitivity, which disallows its independent use. In contrast, OCB showed the highest sensitivity and thus remains the gold standard for the diagnosis of MS.

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.

Prognostic value of cerebrospinal fluid biomarkers in multiple sclerosis: The key role of kappa free light chains and a multivariate predictor for disease progression.

OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with varying progression rates among individuals. The ability to predict disease progression is crucial for treatment decisions with disease-modifying therapies (DMTs). A few cerebrospinal fluid (CSF) biomarkers have been investigated in relation to disease progression, but few have been effectively translated into clinical practice. The aim of this study was to evaluate the diagnostic and prognostic value of known CSF markers, to compare their sensitivity and specificity, and to develop a prognostic model using a combination of markers to predict disease progression. METHODS: This retrospective cohort study included 82 patients with a first episode of inflammatory demyelinating symptoms suggestive of MS between January 2018 and January 2021. Patients underwent diagnostic lumbar puncture and other investigations according to the multiple sclerosis (MS) protocol. They were divided into three groups according to MRI findings, relapse rate and EDSS score. CSF marker concentrations were determined by laser nephelometry and electrochemiluminescence immunoassay. RESULTS: The results showed that the number of oligoclonal bands could discriminate the progression-free group from the other groups, but had a lower discriminatory power compared to CSF marker concentrations. Among CSF markers, FLC kappa showed the best discriminatory performance. By combining FLC kappa with gender and lesion localization information, a simple predictor of progression-free group membership was proposed. This predictor showed good sensitivity (91 %) and specificity (65 %). CONCLUSION: In conclusion, CSF FLC kappa concentration, together with gender and lesion localization, may be a valuable predictor of disease progression in MS patients. This study highlights the potential of using CSF biomarkers for prognostic purposes and offers a simple approach to predicting disease progression.

Síndrome clínico aislado: diagnóstico y riesgo de desarrollar esclerosis múltiple clínicamente definida / Clinically isolated syndrome: diagnosis and risk of developing clinically definite multiple sclerosis

Introducción: La mayoría de los pacientes con esclerosis múltiple (EM) debutan con un síndrome clínico aislado (SCA). Es importante diferenciar este SCA de otras patologías neurológicas agudas o subagudas y estimar el riesgo de desarrollar una esclerosis múltiple clínicamente definida (EMCD), pues un segundo ataque clínico en un corto período de tiempo se asocia con peor pronóstico a largo plazo. Desarrollo: Se realizó una revisión bibliográfica con el objetivo de contrastar diferentes variables, tales como la resonancia magnética (RM) y distintos marcadores biofluídicos como las bandas oligoclonales IgG (BOC), bandas oligoclonales IgM (BOCM), bandas oligoclonales IgM lípido específicas (BOCM-LE), índice de cadenas ligeras libres Kappa (κ index) mediante la determinación de las cadenas ligeras libres kappa en líquido cefalorraquídeo (LCR), neurofilamentos de cadenas ligeras en LCR (NfLL) y suero (NfLS) y la proteína chitinasa 3-like 1 (CHI3L1) en LCR (CHI3L1L) y suero (CHI3L1S), con el objetivo de mejorar la precisión diagnóstica y predecir los riesgos de un segundo ataque clínico tras un SCA. Conclusión: Unas BOC positivas junto con la identificación de lesiones por RM, reducirán el tiempo de diagnóstico y nos indicarán que la mayoría de los pacientes con SCA evolucionarán a EM. Un κ index > 10,6 y una concentración de NfLL > 1.150 ng/L, nos muestran que los SCA tienen más probabilidades de convertirse en EM durante el primer año (40/50%). El 90% de los pacientes con SCA y niveles de CHI3L1S > 33 ng/mL, y el 100% con presencia BOCM-LE se transforman en EM durante el primer año.(AU)

Introduction: In most cases, multiple sclerosis (MS) initially presents as clinically isolated syndrome (CIS). Differentiating CIS from other acute or subacute neurological diseases and estimating the risk of progression to clinically definite MS is essential since presenting a second episode in a short time is associated with poorer long-term prognosis. Development: We conducted a literature review to evaluate the usefulness of different variables in improving diagnostic accuracy and predicting progression from CIS to MS, including magnetic resonance imaging (MRI) and such biofluid markers as oligoclonal IgG and IgM bands, lipid-specific oligoclonal IgM bands in the CSF, CSF kappa free light-chain (KFLC) index, neurofilament light chain (NfL) in the CSF and serum, and chitinase 3–like protein 1 (CHI3L1) in the CSF and serum. Conclusions: Codetection of oligoclonal IgG bands and MRI lesions reduces diagnostic delays and suggests a high risk of CIS progression to MS. A KFLC index > 10.6 and CSF NfL concentrations > 1150 ng/L indicate that CIS is more likely to progress to MS within one year (40-50%); 90% of patients with CIS and serum CHI3L1 levels > 33 ng/mL and 100% of those with lipid-specific oligoclonal IgM bands present MS within one year of CIS onset.

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.

Establishing the best combination of the kappa free light chain index and oligoclonal bands for an accurate diagnosis of multiple sclerosis.

Introduction: The immunoglobulin kappa free light chain (KFLC) index has been proposed as a potentially suitable alternative to oligoclonal IgG bands (OCGB) for diagnosing multiple sclerosis (MS), offering automation and reduced processing time. However, there is no consensus on the preferred approach or how to combine both techniques. Methods: This prospective cohort study aimed to determine the best utilization of OCGB and KFLC index in patients with a clinically isolated syndrome (CIS) followed for at least two years. OCGB and KFLC were assessed using isoelectric focusing and immunoblotting and turbidimetry, respectively. Sensitivity, specificity, and accuracy for diagnosing MS were calculated for each method. Results: The study included 371 patients, with 260 (70.1 %) being women, and a median age of 34.9 (27.8 - 43.9) years. Using a cut-off value of 6.1, the KFLC index demonstrated a sensitivity and specificity of 86.3% and 93.9%, respectively. The sensitivity of OCGB (95.3%) was higher (p < 0.001 vs. KFLC index) and the specificity (100%) was comparable to that of the KFLC index (p = 0.5). The concordance between the methods was not uniform across all patients, with 97.8% agreement in patients with KFLC index ≥ 6.1 and 56.0 % in patients with KFLC index < 6.1. In patients with a KFLC index < 6.1, OCGB still identified 75.0 % of MS patients due to its higher sensitivity. An algorithm using the KFLC index as a screening tool and OCGB as an alternative for patients with a negative KFLC index result achieved an accuracy of 96.3 %. Discussion: Combining the KFLC index and OCGB can provide an easily reproducible and accurate method for diagnosing MS, with OCGB primarily reserved for patients with a KFLC index < 6.1.

Clinically isolated syndrome: Diagnosis and risk of developing clinically definite multiple sclerosis.

INTRODUCTION: In most cases, multiple sclerosis (MS) initially presents as clinically isolated syndrome (CIS). Differentiating CIS from other acute or subacute neurological diseases and estimating the risk of progression to clinically definite MS is essential since presenting a second episode in a short time is associated with poorer long-term prognosis. DEVELOPMENT: We conducted a literature review to evaluate the usefulness of different variables in improving diagnostic accuracy and predicting progression from CIS to MS, including magnetic resonance imaging (MRI) and such biofluid markers as oligoclonal IgG and IgM bands, lipid-specific oligoclonal IgM bands in the CSF, CSF kappa free light-chain (KFLC) index, neurofilament light chain (NfL) in the CSF and serum, and chitinase 3-like protein 1 (CHI3L1) in the CSF and serum. CONCLUSIONS: Codetection of oligoclonal IgG bands and MRI lesions reduces diagnostic delays and suggests a high risk of CIS progression to MS. A KFLC index > 10.6 and CSF NfL concentrations > 1150 ng/L indicate that CIS is more likely to progress to MS within one year (40%-50%); 90% of patients with CIS and serum CHI3L1 levels > 33 ng/mL and 100% of those with lipid-specific oligoclonal IgM bands present MS within one year of CIS onset.

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.

Kappa free light chains index in multiple sclerosis very long-term prognosis.

Introduction: The role of the kappa-free light chain (kFLC) in the diagnosis of multiple sclerosis (MS) and, to a lesser extent, its role as a medium-term prognostic marker have been extensively studied. This study aimed to explore its potential as a long-term prognostic marker for MS. Methods: We performed an exploratory retrospective observational study by selecting patients systemically followed up in our MS unit with available cerebrospinal fluid and serum samples at the time of initial evaluation. Two groups were defined: benign MS (bMS), defined as patients with Expanded Disability Status Scale (EDSS) ≤ 3 at 10 years of follow-up, and aggressive MS (aMS), defined as patients with EDSS ≥ 6 at 15 years of follow-up. Clinical variables were collected, and the immunoglobulin G (IgG) index, kFLC index, and oligoclonal bands (OCB) were determined for all patients and compared between the groups. Results: Twenty bMS and 15 aMS patients were included in this study. Sixty percent (21/35) were female, and the mean age at the time of the first symptom was 31.5 ± 9.45 years, with no statistical differences between groups. Median follow-up time was 19.8 years (Interquartile range, IQR 15.9-24.6). The median EDSS scores at the last follow-up were 1.5 and 7.5 in the bMS and the aMS group, respectively. No statistically significant differences were found in the kFLC index between the two groups (136.6 vs. 140.27, p=0.59). The IgG index was positive in 62.9% of patients (55% bMS vs. 73.3% aMS, p>0.05), and OCB was positive in 88.6% (90% bMS vs. 86.7% aMS, p>0.05). A significant positive correlation was found between IgG and kFLC indices (rs = 0.85, p<0.001). Conclusion: Given the absence of differences between the two groups with opposite disease courses, it is unlikely that the kFLC index is a reliable and powerful marker of long-term prognosis in MS.