OBJECTIVE: To investigate the value of serum free light chain (sFLC) and serum calcium ion in the diagnosis and prognosis of multiple myeloma (MM).
METHODS: Forty patients with MM treated in Henan Provincial People\'s Hospital from January 2018 to January 2022 were selected as the observation group, and 40 healthy volunteers were selected as the control group. The differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc between the two groups were compared. Meanwhile, the differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc in different international staging systems (ISS), chemotherapy efficacy and prognosis patients were analyzed.
RESULTS: The levels of sFLC-κ［(98.39±21.19) vs (12.01±4.45) mg/L］, sFLC-λ［(210.20±45.54) vs (14.10±5.11) mg/L］ and proportions of hypocalcemia （65% vs 0） in the observation group were significantly higher than those in the control group (P < 0.05), while sFLC-κ/ λ ratio［（0.44±0.10） vs (0.87±0.12)］ and serum calcium ions ［（1.98±0.46） vs （2.42±0.40）mmol/L］ were significantly lower than those in the control group (P < 0.05). The sFLC-κ, sFLC-λ, the proportion of hypocalcemia and the course of hypocalcemia in ISS stage III patients in the observation group were significantly higher than those in stage I and II patients (P < 0.05), while sFLC-κ/λ ratio, and serum calcium ions were significantly lower than those in stage I and II patients (P < 0.05). The levels of sFLC-κ ［（107.76±21.22） vs （94.67±20.11）mg/L］, sFLC- λ［（245.54±41.12） vs （205.54±50.22）mg/L］ of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia (P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia ［（0.42±0.04） vs （0.47±0.06）；P < 0.05］. The levels of sFLC-κ ［(107.29±20.14） vs （ 91.11±18.92）mg/L］, sFLC-λ［（247.98±42.26） vs （179.29±39.32）mg/L］ in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy (P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy ［(0.43±0.10) vs (0.50±0.09)；P < 0.05）］. The area under the ROC curve for sFLC-κ, sFLC-λ, sFLC-κ/λ predicting ineffective chemotherapy was 0.803, 0.793 and 0.699 respectively, P < 0.05. There was no significant difference in sFLC-κ, sFLC-λ, sFLC-κ/λ ratio, serum calcium ion, hypocalcemia ratio and hypocalcemia course between survival and death patients (P >0.05).
CONCLUSIONS: sFLC and serum calcium are related to ISS stage of MM patients. sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients. However, the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.
UNASSIGNED: sFLC、血清钙离子在多发性骨髓瘤患者诊断及预后判断中的应用价值.
UNASSIGNED: 探讨血清游离轻链（sFLC）、血清钙离子在多发性骨髓瘤（MM）患者诊断及预后中的临床应用价值。.
UNASSIGNED: 选取2018年1月至2022年1月在河南省人民医院治疗的MM患者40例作为观察组，同时选取健康志愿者40例作为对照组，比较两组患者的sFLC-κ、sFLC-λ、sFLC-κ/λ、血清钙离子等差异性，同时分析观察组不同国际分期系统（ISS）、不同化疗疗效及不同预后患者的sFLC-κ、sFLC-λ、sFLC-κ/λ、血清钙离子等差异性。.
UNASSIGNED: 观察组sFLC-κ水平［（ 98.39±21.19）对(12.01±4.45）mg/L］、sFLC-λ水平［（210.20±45.54）对（14.10±5.11）mg/L］、低钙血症比例（65%对0）均明显高于对照组（P < 0.05），而sFLC-κ/λ比值［（0.44±0.10）对（0.87±0.12）］、血清钙离子［（1.98±0.46）对（2.42±0.40）mmol/L］明显低于对照组（P < 0.05）。观察组ISS分期Ⅲ期患者sFLC-κ、sFLC-λ浓度、低钙血症比例和低钙血症病程均明显高于Ⅰ期和Ⅱ期患者（P < 0.05），而sFLC-κ/λ、血清钙离子均明显低于Ⅰ期和Ⅱ期患者（P < 0.05）。观察组有低钙血症患者sFLC-κ水平［（107.76±21.22）对（94.67±20.11）mg/L］、sFLC-λ水平［（245.54±41.12）对（205.54±50.22）mg/L］明显高于无低钙血症患者（P < 0.05），而sFLC-κ/λ比值明显低于无低钙血症患者［（0.42±0.04）对（0.47±0.06）；P < 0.05］。化疗无效患者sFLC-κ水平［（107.29±20.14）对（91.11±18.92）mg/L］、sFLC-λ水平［（247.98±42.26）对（179.29±39.32）mg/L］明显高于化疗有效患者（P < 0.05），而sFLC-κ/λ比值明显低于化疗有效患者［（0.43±0.10）对（0.50±0.09）；P < 0.05）］。sFLC-κ、sFLC-λ、sFLC-κ/λ预测化疗无效的ROC曲线下面积分别为0.803、0.793和0.699，P < 0.05。存活和死亡患者的sFLC-κ、sFLC-λ、sFLC-κ/λ、血清钙离子、低钙血症比例和低钙血症病程比较差异无统计学意义（均P ＞0.05）。.
UNASSIGNED: sFLC、血清钙离子与MM患者ISS分期有关，sFLC水平在预测MM患者化疗疗效方面有一定应用价值，sFLC与血清钙离子在判断MM患者预后方面暂未发现有应用价值。.

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.

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.

OBJECTIVE: To study intrathecal kappa free light chain (KFLC) synthesis in people living with HIV (PLWH) in comparison with multiple sclerosis (MS).
METHODS: Cross-sectional analysis including 56 untreated and 150 well treated PLWH, and compared with 58 controls, and 223 MS patients.
RESULTS: Elevated serum/cerebrospinal fluid (CSF) IgG and KFLC indices were observed in untreated PLWH. Seventy percent of untreated PLWH had KFLC index above 6.1, a threshold associated with clinically isolated syndrome/MS diagnosis. No association was found between KFCL index and CSF markers of neuronal injury in either PLWH or MS patients.
CONCLUSIONS: HIV-related immune system dysfunction is often associated with an elevated KFLC index akin to those observed in MS. HIV infection should be considered as a differential diagnosis for patients presenting with neurological symptoms and increased intrathecal immunoglobulin synthesis.

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.

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.
UNASSIGNED:
RESULTS: In this report, we describe five cases of MM synchronous with lung adenocarcinoma including λ light chain in three cases and ϰ light chain in two cases. Two patients achieved complete remission, and no progression was seen in two patients.
CONCLUSIONS: 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.

暂无摘要。

The two most common systemic amyloidosis types are immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) amyloidosis, in which the precursor proteins responsible for amyloidosis are light chain and transthyretin, respectively. Identification of precursor proteins is paramount to determine the type of amyloidosis, given that both amyloidosis types lack specificity in clinical presentation. Congo red staining followed by immunohistochemistry or immunofluorescence using fibril protein-specific antibodies is crucial for the diagnosis of amyloidosis. Here we describe a patient who was initially diagnosed with AL amyloidosis due to strong positive kappa light chain staining results. However, the diagnosis was corrected to hereditary ATTR amyloidosis using mass spectrometry and gene sequencing, confirming the important role of mass spectrometry in identifying the amyloid precursor protein and ruling out false-positive result from immunohistochemistry.

BACKGROUND: While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing-remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA).
METHODS: We retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models.
RESULTS: KFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9-253.5) compared with non-PIRA (78.26, IQR 28.93-186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002-1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up.
CONCLUSIONS: Our data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS.

OBJECTIVE: To explore the clinical and pathological features of light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-LC).
METHODS: From January 2010 to December 2022, patients who were diagnosed with PGNMID-LC were selected, and their clinical and pathological features were retrospectively analysed.
RESULTS: Three males aged 42-61 years old were enrolled. Hypertension was present in three patients, oedema in three patients, anaemia in two patients, proteinuria in three patients, nephrotic syndrome in one patient, microscopic haematuria in three patients, renal insufficiency in two patients and hypocomplementaemia of C3 in one patient. Elevated serum-free LC ratios and plasmacytosis on bone marrow smears were observed in three patients, and κ was identified by serum protein immunofixation electrophoresis in one patient. Renal biopsy showed membranoproliferative glomerulonephritis in two patients and endocapillary proliferative glomerulonephritis in one patient on light microscopy. Immunofluorescence indicated restricted κ LC and C3 distributed in glomeruli. By electron microscopy, electron-dense deposits without substructure were identified predominantly in the mesangial and subendothelial regions and were variable in the subepithelial region. Two patients were treated with plasma cell-directed chemotherapy and achieved haematological complete response or very good partial response, and one of them achieved a renal status of complete remission. One patient treated with immunosuppressive therapy only did not achieve haematological or renal remission.
CONCLUSIONS: PGNMID-LC is a rare and uniform disease with a high frequency of a detectable pathogenic plasma cell clone and is characterised by glomerular deposition of restricted LC and C3 in renal pathology. Plasma cell-directed chemotherapy may improve haematological and renal prognosis.