Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon and Hospices Civils de Lyon, Lyon, France.
Hospices Civils de Lyon, France.
Arthritis Rheumatol. 2019 Nov;71(11):1904-1912. doi: 10.1002/art.41003. Epub 2019 Sep 20.
Cryoglobulins are cold-precipitating immunoglobulins. Through progress in techniques, we undertook this study to update information on the biologic characteristics of cryoglobulins in a very large population.
A cohort of 13,439 patients was tested for cryoglobulins from January 2010 to December 2016. The analysis included cryoglobulin isotype, clonality, concentration, and IgM rheumatoid factor (IgM-RF) in cryoprecipitate, as well as serum complement and RF. Markers of gammopathy, viral infection, and autoimmunity were also investigated.
Of the 13,439 patients, 1,675 (12.5%) tested positive for cryoglobulins: 155 patients (9.3%) with type I, 788 (47%) with type II, and 732 (43.7%) with type III cryoglobulins. Nine percent of patients who were retested after initially testing negative for cryoglobulins showed a positive result on a follow-up test (196 of the 2,213 retested patients). In type I cryoglobulins, IgM was more frequent but occurred at lower concentrations than IgG. Mixed cryoglobulins were found in 34.8% of the tested patients who were positive for hepatitis C virus and <5% of those who were positive for hepatitis B virus or HIV. Of the patients with anti-double-stranded DNA, anti-SSA, or anti-cyclic citrullinated peptide autoantibodies, 25.4% tested positive for mixed cryoglobulins, with type III occurring more frequently than type II. Both cryoprecipitate and serum were RF-positive in 21.6% of type II and 10.1% of type III cryoglobulins. A decrease of C4, with or without accompanying decreases of C3 and CH50, was found in 23.6% of cryoglobulin samples.
Obtained with the use of modern assays, our findings from this very large collection of cryoglobulins provide an update on cryoglobulin distribution and characteristics, with minimal selection bias. Despite strict preanalytical conditions, a negative finding for the presence of cryoglobulin must be confirmed in a second sample. RF activity and complement decreases were rarely detected.
冷球蛋白是遇冷沉淀的免疫球蛋白。通过技术的进步，我们进行了这项研究，以更新大量人群中冷球蛋白的生物学特征信息。
我们对 2010 年 1 月至 2016 年 12 月期间的 13439 例患者进行了冷球蛋白检测。分析包括冷球蛋白的同种型、单克隆性、浓度以及冷沉淀中的 IgM 类风湿因子（IgM-RF），以及血清补体和 RF。还研究了丙种球蛋白病、病毒感染和自身免疫的标志物。
在 13439 例患者中，有 1675 例（12.5%）冷球蛋白检测阳性：155 例（9.3%）为 I 型，788 例（47%）为 II 型，732 例（43.7%）为 III 型。在最初冷球蛋白检测为阴性的 2213 例患者中，有 196 例（9%）在随访检测中结果为阳性。在 I 型冷球蛋白中，IgM 更常见，但浓度低于 IgG。在 HCV 阳性患者中，混合性冷球蛋白占 34.8%，而在 HBV 或 HIV 阳性患者中，混合性冷球蛋白<5%。在有抗双链 DNA、抗 SSA 或抗环瓜氨酸肽自身抗体的患者中，25.4%的患者混合性冷球蛋白阳性，III 型比 II 型更常见。在 21.6%的 II 型和 10.1%的 III 型冷球蛋白中，冷沉淀和血清均为 RF 阳性。在 23.6%的冷球蛋白样本中发现 C4 下降，伴有或不伴有 C3 和 CH50 下降。
本研究使用现代检测方法，从大量冷球蛋白样本中获得的结果，提供了冷球蛋白分布和特征的最新信息，几乎没有选择偏倚。尽管严格控制了分析前条件，但冷球蛋白存在的阴性发现必须在第二个样本中得到确认。很少检测到 RF 活性和补体减少。
