抗核抗体和冷球蛋白在急性和慢性戊型肝炎病毒感染患者中的意义
Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection.
作者信息
Horvatits Thomas, Schulze Zur Wiesch Julian, Polywka Susanne, Buescher Gustav, Lütgehetmann Marc, Hussey Elaine, Horvatits Karoline, Peine Sven, Haag Friedrich, Addo Marylyn M, Lohse Ansgar W, Weiler-Normann Christina, Pischke Sven
机构信息
I. Department of Medicine, Gastroenterology and Hepatology, with the Sections Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 20359 Hamburg, Germany.
出版信息
Pathogens. 2020 Sep 16;9(9):755. doi: 10.3390/pathogens9090755.
BACKGROUND
Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection.
METHODS
The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection.
RESULTS
Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors ( = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients.
CONCLUSION
In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E.
背景
戊型肝炎病毒（HEV）与免疫现象有关。然而，它们的临床意义仍有待阐明，即冷球蛋白或自身抗体是否会影响HEV感染个体的显性疾病。为了更好地理解，我们在三个队列中分析了这些不同的免疫现象，每个队列代表不同类型的HEV感染。
方法
这些队列包括：（i）免疫功能正常的急性戊型肝炎患者，（ii）免疫抑制的慢性戊型肝炎患者，以及（iii）无症状HEV感染个体。他们总共57人，回顾性研究抗核抗体（ANA）、冷球蛋白和血清总IgG的存在情况。然后将他们与17名未治疗的慢性乙型肝炎病毒（HBV）感染或丙型肝炎病毒（HCV）感染患者的对照队列进行比较。
结果
13名（23%）是免疫功能正常的急性戊型肝炎患者（丙氨酸转氨酶（ALT）中位数 = 872 U/L），15名（26%）是免疫抑制的慢性戊型肝炎患者（ALT中位数 = 137 U/L），29名（51%）是无症状HEV感染的献血者（ALT中位数 = 35 U/L）。总体而言，24%的患者ANA滴度>1:160检测呈阳性，11%呈现特定的ANA模式。ANA检测与HEV感染类型、IgG水平、性别或年龄无关。所有个体抗线粒体抗体、抗中性粒细胞胞浆抗体、肝肾微粒体抗体、抗髓过氧化物酶和抗蛋白酶3抗体检测均为阴性。5名患者（9%）冷球蛋白检测呈阳性。值得注意的是，冷球蛋白血症存在于显性戊型肝炎患者中（（i）组和（ii）组；1例急性和4例慢性HEV感染），但在任何无症状献血者中均不存在（P = 0.02）。HEV患者与HBV/HCV患者冷球蛋白和ANA升高的频率没有显著差异。
结论
与HBV和HCV感染的研究结果一致，我们经常观察到与HEV感染相关的ANA（24%）和冷球蛋白（9%）检测。冷球蛋白的存在仅限于显性戊型肝炎患者。我们补充了戊型肝炎免疫现象的研究结果。
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