Immunoglobulin lambda-Chains

免疫球蛋白 λ 链
  • 文章类型: English Abstract
    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。.
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  • 文章类型: Journal Article
    近年来,在慢性淋巴细胞白血病(CLL)中检测微小/可测量的残留病(MRD)的重要性由于高效治疗药物的可用性而增加.流式细胞术提供了显着的成本效益和即时性,预期灵敏度水平约为10-4。通过流式细胞术检测MRD的关键方面在于准确定义含有肿瘤细胞的区域。然而,CLL的一个子集,称为具有非典型免疫表型的CLL,表现出独特的细胞表面标记表达模式,可以使MRD检测具有挑战性,因为这些标记通常与正常B细胞相似。为了提高MRD在此类非典型CLL病例中检测的灵敏度,我们利用了细胞表面免疫球蛋白(sIg)轻链在该亚型中倾向于以更高的水平表达的观察结果。对于每四个细胞表面标记的二维图,我们使用曲线图评估sIgκ/λ轻链的表达,并确定了sIg轻链的κ/λ比值偏离假定CLL细胞区域内指定阈值的区域.使用此方法,我们可以检测到10-4水平的非典型CLL细胞。我们提出这种方法作为一种有效的MRD检测方法。
    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.
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  • 文章类型: Journal Article
    尽管基因和功能研究取得了进展,常见变异型免疫缺陷(CVID)的及时诊断仍是一项重大挑战.这项探索性研究旨在评估一组新型的CVID生物标志物的诊断性能,结合κ+λ轻链的总和,可溶性B细胞成熟抗原(sBCMA)水平,转换记忆B细胞(smB)和视觉评分。利用逻辑回归进行比较分析,以建立黄金标准测试,特别是抗体反应。我们的研究涵盖了88个主题,包括27个CVID,23选择性IgA缺乏症(SIGAD),20例继发性免疫缺陷(SID)患者和18例健康对照。我们建立了sBCMA的诊断准确性和κ+λ的总和,实现89%和89%的灵敏度(Se)和特异性(Spe),90%和99%,分别。重要的是,sBCMA与所有评估的生物标志物显示出强相关性(总和κ+λ,smB细胞和视觉),而κ+λ的总和是唯一独立于smB细胞或VISUAL的,提示其额外的诊断价值。通过多变量树决策模型,特异性抗体反应和κ+λ的总和是独立的,CVID的特征生物标志物,该模型显示曲线下面积(AUC)为0.946,Se0.85和Spe0.95。这种树决策模型有望提高CVID的诊断效率,强调和κ+λ作为面板内优越的CVID分类器和潜在的诊断标准。
    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.
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  • 文章类型: Journal Article
    背景:人类免疫缺陷病毒(HIV)感染与明显的氧化应激有关,导致各种病毒相关病理的发展。大量证据表明,以及活性氧调节的规范酶,人体血液中含有过氧化物酶抗体,超氧化物歧化酶,和过氧化氢酶活性。在这里,我们显示IgG的过氧化氢酶活性及其κκ-IgG,λλ-IgG,与健康供体相比,HIV感染个体的κλ-IgG亚组分显着不同。
    方法:蛋白G-Sepharose吸附剂用于通过亲和层析从健康供体和HIV感染患者的血液中分离IgG。κκ-IgG亚组分,λλ-IgG,通过在含有固定的κ或λ轻链抗体的吸附剂上进行亲和层析,从每组的IgG样品中分离出κλ-IgG。通过评估由于过氧化氢分解导致的光密度(A240)的降低,用分光光度法测量IgG过氧化氢酶活性水平。
    结果:HIV感染患者抗体的相对过氧化氢酶活性(kcat=(1.41±0.92)×103min-1,95%CI:[1.01-1.81])具有统计学意义,与明显健康的供体((0.86±0.49)×103,95%CI:[0.69-1.03])相比,高出1.6倍(p=0.014)。HIV感染患者的κκκ-IgG活性水平((0.44±0.04)×103min-1)是λλ-IgG的1.4倍((0.31±0.025)×103min-1);对于明显健康的供体,观察到相反的情况。与λλ-IgG((0.53±0.045)×103min-1)相比,其活性((0.17±0.015)×103min-1)低3.1倍。
    结论:因此,获得的数据可能表明,过氧化氢酶活性增加的IgG可以预防HIV感染患者氧化应激引起的有害过程,作为调节过氧化氢水平的附加天然分子机制。
    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.
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  • 文章类型: Case Reports
    背景:多发性骨髓瘤(MM)是一种恶性疾病,其特征是单克隆分化的浆细胞。虽然它更常见于老年人,它也会影响年轻人群,虽然发病率较低。
    方法:这里,我们介绍了一名32岁女性被诊断患有IgAλMM的病例。她表现出疲劳,恶心,急性肾损伤(AKI)与肌酐快速增加,和贫血。进行了肾活检以排除快速进展的肾小球疾病,从而获得了诊断。遗传检查显示t(14;16)易位和TP53的额外拷贝。患者接受了积极的静脉类固醇和静脉液体复苏,导致肾功能的改善。达雷妥单抗联合硼替佐米治疗,沙利度胺,开始使用地塞米松,并且耐受性良好。尽管IgAMM的预后普遍较差,我们的病例强调了对不明原因肾损伤的年轻患者考虑MM的重要性.
    结论:早期识别和及时干预对于治疗MM患者至关重要,尤其是那些有高风险的细胞遗传学异常。此病例提醒临床医生保持对MM的高度怀疑,即使在年轻人群中,当出现无法解释的肾损伤时。
    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.
    METHODS: 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.
    CONCLUSIONS: 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.
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  • 文章类型: Letter
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  • 文章类型: Case Reports
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  • 文章类型: Case Reports
    苔藓粘液症(LM)是一种慢性皮肤粘液病,可表现为局部皮肤病变或全身性全身性疾病,称为巩膜水肿。鉴别诊断取决于临床表现的组合,血清学研究,和组织病理学检查。目前,尚未阐明将局部LM与巩膜水肿区分开来的公认和公认的组织病理学特征。我们最近的出版物,以及回顾性文献综述,提示轻链限制性浆细胞群的存在代表了诊断局部LM的独特组织病理学线索。在这份报告中,我们提供了另外两个带有λ轻链限制性浆细胞的局部LM病例,以及与我们以前的出版物相似的临床和组织病理学发现。这些病例支持我们的理论,即轻链限制的浆细胞微环境主要归因于局部LM的发病机理。因此,我们认为这些病例构成了局部LM的临床和病理新变体,并将其命名为具有轻链限制性浆细胞的原发性局部皮肤LM。
    Lichen myxedematosus (LM) is a chronic cutaneous mucinosis that can present as a localized skin lesion or as a generalized systemic disease termed scleromyxedema. The differential diagnosis is determined by a combination of clinical presentation, serological studies, and histopathological examination. Currently, well-established and accepted histopathological features to distinguish localized LM from scleromyxedema have not been elucidated. Our recent publication, together with a retrospective literature review, suggests that the presence of groups of light chain-restricted plasma cells represents a distinct histopathological clue for the diagnosis of localized LM. In this report, we provide two additional cases of localized LM with lambda light chain-restricted plasma cells, together with clinical and histopathological findings that are similar to our previous publication. These cases support our theory that the light chain-restricted plasmacytic microenvironment is primarily attributed to the pathogenesis of localized LM. Therefore, we consider these cases to constitute a clinically and pathologically new variant of localized LM and name it primary localized cutaneous LM with light chain-restricted plasma cells.
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  • 文章类型: Case Reports
    所有症状性多发性骨髓瘤(MM)中不到2%具有免疫球蛋白D(IgD)作为单克隆蛋白。双态丙种球蛋白病要罕见得多。在诊断的时候,疾病往往处于晚期,包括肾衰竭,贫血,高钙血症和溶解性骨病变。由于骨髓瘤本身的稀有性,而且由于抗IgD抗血清不用于常规实践,文献中只有少数IgDMM的报道。该病例报告描述了患有IgDλMM的贫血和肾衰竭的患者。贫血,肾功能衰竭,我们的IgDlambdaMM患者的骨活检中>80%的浆细胞符合国际骨髓瘤工作组的MM诊断标准。患者的临床过程与其他IgDMM患者相似。血清蛋白免疫固定(s-IFE)的最终结果显示IgDλ和游离λ单克隆条带。为了防止误诊,有必要使用抗IgD和抗IgE抗血清,IgM,IgG,κ和λ抗血清显示κ或λ单克隆带,重链中没有单克隆带。
    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.
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  • 文章类型: Journal Article
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