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

中文翻译：

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常见的可变免疫缺陷疾病中的血清游离轻链：在鉴别诊断和与临床表型的关联中的作用。

我们报告了一项对345名成人CVID患者的观察性，多中心研究，旨在评估常见变量免疫缺陷疾病（CVID）的诊断价值和血清游离轻链（sFLC）模式的临床关联。对60名CVID患者进行了两次测试，以评估sFLC的个体差异。作为对照组，我们包括138例患者，这些患者受到不确定的一抗抗体缺陷（UAD），淋巴组织增生性疾病（LPD）和与血液系统恶性肿瘤（SID）不相关的二抗抗体缺乏症的影响。与对照组相比，CVID患者的κ和λ链浓度较低，个体内sFLC变异性较低。根据sFLC模式，将患者分为四组：κ-λ+，κ+λ-，κ-λ-，κ+λ+。在CVID患者中，最常见的模式是κ-λ-（51％），其次是κ-λ+，（25％），κ+λ+（22％）和κ+λ-（3％）。在UAD，LPD和SID组中，κ+λ+是最常见的模式。通过分析sFLC模式与CVID的疾病相关并发症之间的可能联系，我们观察到与κ+λ+组相比，属于κ-λ-组的患者出现更常见的原因不明的肠病，与之相比，支气管扩张和脾肿大的发生率更高对于κ-λ+和κ+λ+患者。与其他组相比，κ-λ-在诊断时血清IgG，IgA和IgM浓度也较低，CD27 + IgD-IgM转换记忆B细胞的频率较低，而CD21low B细胞的频率较高，接受较早的CVID诊断。因此，较低水平的sFLC可能是B细胞分化受损的表象，可能导致κ-λ-患者患细菌感染和慢性肺损伤的风险更高。根据这些结果，我们建议将sFLC测定法添加到低血球蛋白血症的诊断性检查和随访期间。该测定法可能有助于区分CVID与其他原因的低球蛋白血症，并早期检测多年来发生的单克隆淋巴细胞增殖。此外，由于sFLC模式似乎与CVID的疾病表型和临床表现有关，并且在进一步研究证实后，sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。我们建议将sFLC测定法添加到低血球蛋白血症的诊断性检查以及随访期间。该测定法可能有助于区分CVID与其他原因的低球蛋白血症，并早期检测多年来发生的单克隆淋巴细胞增殖。此外，由于sFLC模式似乎与CVID的疾病表型和临床表现有关，并且在进一步研究证实后，sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。我们建议将sFLC测定法添加到低血球蛋白血症的诊断性检查以及随访期间。该测定法可能有助于区分CVID与其他原因的低球蛋白血症，并早期检测多年来发生的单克隆淋巴细胞增殖。此外，由于sFLC模式似乎与CVID的疾病表型和临床表现有关，并且在进一步研究证实后，sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。该测定法可能有助于区分CVID和其他原因的低血球蛋白血症，并能早期检测多年来发生的单克隆淋巴细胞增殖。此外，由于sFLC模式似乎与CVID的疾病表型和临床表现有关，并且在进一步研究证实后，sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。该测定法可能有助于区分CVID和其他原因的低球蛋白血症，并能早期检测出多年来发生的单克隆淋巴细胞增殖。此外，由于sFLC模式似乎与CVID的疾病表型和临床表现有关，并且在进一步研究证实后，sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。sFLC测定法可能被认为是鉴定有较高患肠病和慢性肺损伤或脾肿大风险的患者的预后工具。这将允许为CVID患者设计量身定制的随访。