Deng Xiaoli, Crowson Cynthia S, Rajkumar S Vincent, Dispenzieri Angela, Larson Dirk R, Therneau Terry M, Matteson Eric L, Kyle Robert A, Katzmann Jerry A, Gabriel Sherine E, Davis John M
From the Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China; Department of Health Sciences Research, Department of Medicine, and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.X. Deng, MD, Department of Rheumatology and Immunology, Peking University Third Hospital, and formerly Research Trainee, Division of Rheumatology, Departments of Medicine and Immunology, Mayo Clinic; C.S. Crowson, MS, Associate Professor of Medicine, Assistant Professor of Biostatistics; T.M. Therneau, PhD, Professor of Biostatistics, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research; S.V. Rajkumar, MD, Professor of Medicine, Division of Hematology, Department of Medicine; A. Dispenzieri, MD, Professor of Medicine, Professor of Laboratory Medicine and Pathology; R.A. Kyle, MD, Professor of Medicine, Professor of Laboratory Medicine and Pathology, Division of Hematology, Department of Medicine; E.L. Matteson, MD, MPH, Professor of Medicine; S.E. Gabriel, MD, MSc, Professor of Epidemiology, Professor of Medicine, Division of Rheumatology, Department of Medicine, Division of Epidemiology, Department of Health Sciences Research; J.M. Davis III, MD, MS, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine; J.A. Katzmann, PhD, Assistant Professor of Microbiology, Associate Professor of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, and the Mayo Clinic College of Medicine; D.R. Larson, MS, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic.
J Rheumatol. 2015 Feb;42(2):181-7. doi: 10.3899/jrheum.140543. Epub 2015 Jan 15.
Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLC to preclinical disease, RA characteristics, and mortality in RA compared to non-RA subjects.
A population-based study in Olmsted County, Minnesota, USA, was performed by crosslinking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLC and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLC, disease characteristics, and mortality, testing for differential effects of FLC on mortality in RA.
Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLC were significantly higher in RA compared to non-RA subjects (4.2 vs 3.3 mg/dl, p < 0.001). FLC became elevated 3-5 years before the clinical onset of RA and remained elevated during followup. Polyclonal FLC were found to predict higher mortality in persons with RA, though elevation to the highest decile had a relatively lower effect on mortality in RA compared to non-RA subjects.
Elevation of serum FLC precedes the development of RA and may be useful in monitoring B cell activity and disease progression. FLC are associated with mortality among patients with RA as well as the general population.
免疫球蛋白游离轻链（FLC）是类风湿关节炎（RA）中B细胞活性的生物标志物，且与普通人群的全因死亡率相关。我们的目的是评估血清FLC与临床前期疾病、RA特征以及RA患者与非RA患者死亡率之间的关系。
在美国明尼苏达州奥尔姆斯特德县进行了一项基于人群的研究，通过将普通人群中可进行血清FLC测量的大型队列与已确定的RA发病率和患病率队列进行交叉关联。比较了RA患者和非RA患者之间的血清κ、λ和总FLC及其相对于RA发病率的趋势。使用回归模型确定FLC、疾病特征和死亡率之间的关联，测试FLC对RA患者死亡率的差异影响。
在16,609名受试者中，270名在进行FLC测量时符合RA标准。RA患者的平均总FLC显著高于非RA患者（4.2 vs 3.3 mg/dl，p < 0.001）。FLC在RA临床发作前3 - 5年升高，并在随访期间持续升高。发现多克隆FLC可预测RA患者的较高死亡率，尽管与非RA患者相比，升高至最高十分位数对RA患者死亡率的影响相对较低。
血清FLC升高先于RA的发生，可能有助于监测B细胞活性和疾病进展。FLC与RA患者以及普通人群的死亡率相关。
