The Prevalence of Antinuclear Antibodies in the General Population of China: A Cross-Sectional Study

Guo, BS Ya-Ping; Wang, Chunguang; Liu, Xin; Huang, BS Yi-Qian; Guo, BS De-Li; Jing, BS Xing-Zhuo; Yuan, Chun-Gang; Yang, BS Song; Liu, BS Jin-Mei; Han, BS Meng-Si; Li, Hongxing

doi:10.1016/j.curtheres.2014.06.004

Cited by 78 publications

(65 citation statements)

References 18 publications

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“…There are reports of pre-symptomatic patients displaying serum autoantibodies up to 20 years prior onset of an autoimmune disease, for example, anti-TRIM21 reactivity related to Sj€ ogren syndrome [17] and anti-citrullinated-peptide antibodies (ACPA) related to rheumatoid arthritis [18]. Several studies have shown that healthy individuals have detectable levels of serum autoantibodies which suggests that autoantibody positivity is not necessarily disease associated [19][20][21][22][23][24][25][26][27][28][29]. It remains to be seen if any of the individuals we have investigated herein develop autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Individual and stable autoantibody repertoires in healthy individuals

et al. 2019

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In the era towards precision medicine, we here present the individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG signatures are stable over time in a way that each individual profile is recognized in longitudinal sampling. The IgG autoantibody reactivity towards an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured in longitudinal plasma samples from 193 healthy individuals. This analysis resulted in unique autoantibody barcodes for each individual that were maintained over one year's time. The reactivity profiles, or signatures, are person specific in regards to the number of reactivities and antigen specificity. Two independent data sets were consistent in that each healthy individual displayed reactivity towards 0-16 antigens, with a median of six. Subsequently, four selected individuals were profiled on in-house produced high-density protein arrays containing 23,000 protein fragments representing 14,000 unique protein coding genes. Based on a unique, broad and deep longitudinal profiling of autoantibody reactivities, our results demonstrate a unique autoreactive profile in each analyzed healthy individual. The need and interest for broad-ranged and high-resolution molecular profiling of healthy individuals is rising. We have here generated and assessed an initial perspective on the global distribution of the self-reactive IgG repertoire in healthy individuals, by investigating 193 well-characterized healthy individuals. HIGHLIGHTSA unique longitudinal profiling of autoantibody repertoires in healthy individuals Autoantibody profiles are highly individual and stable over time All individuals display IgG binding to human protein fragments The specificity of disease associated autoantigens needs to be thoroughly characterized The identification of a small set of highly reactive autoantigens Importance of stringent antigen and sample specific cut-offs for defining reactivity ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Individual and stable autoantibody repertoires in healthy individuals

et al. 2019

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“…However, we found no evidence of bias regarding frequencies of liver biopsies that could explain more severe autoimmune hepatitis features in women aged <50 vs. women aged ≥50 and men (Tables , ); the study population appeared to have similar proportions of positive ANA in each age/gender category as compared to the excluded population (interaction P =.29). Positive ANA is observed among healthy general population . Thus whether positive ANA is an innocent bystander, or a risk factor of developing hepatotoxicity, or a consequence of hepatotoxicity observed in a subgroup of patients is uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Positive ANA is observed among healthy general population. 19,20 Thus whether positive ANA is an innocent bystander, or a risk factor of developing hepatotoxicity, or a consequence of hepatotoxicity observed in a subgroup of patients is uncertain. Numbers of iron-positive hepatocytes were the highest in men, intermediate in women ≥50 years, and the lowest in women <50 years of age.…”

Section: Discussionmentioning

confidence: 99%

Associations of gender and a proxy of female menopausal status with histological features of drug‐induced liver injury

Suzuki

Barnhart

et al. 2017

Liver International

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Background and aim Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] with histologic features of liver injury in 212 adults enrolled in the Drug-Induced Liver Injury Network (DILIN) registry. Methods All participants had a causality score of at least ‘probable’, a liver biopsy within 30 days of DILI onset, and no prior chronic liver disease. Biochemical and histologic injury types were classified as hepatocellular or cholestatic/mixed injury. The cohort was divided into three gender/age categories: men (41.0%), women < 50 years (27.4%), and women ≥ 50 years of age (31.6%). Interaction of gender and age category (≥50 or not) was assessed. Results Hepatocellular injury was more prevalent in women < 50 years vs. others (p=0.002). After adjusting for biochemical injury types, black race and possible aging effects, more severe interface hepatitis was noted in biopsies of women < 50 years compared to those of men and women ≥ 50 years (p=0.009 and p=0.055, respectively). Compared to those of men, biopsies of women showed greater plasma cell infiltration, hepatocyte apoptosis, hepatocyte rosettes, and lobular disarray but less iron-positive hepatocytes and histological cholestasis (p<0.05). These associations persisted after excluding cases of amoxicillin/clavulanic acid, anabolic steroids or nitrofurantoin DILI which showed gender-specific distributions. Conclusion Gender and a proxy of menopause were associated with various features of inflammation and injury in DILI.

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“…7,13 Although anti-Ro/SSA-positive CTD patients frequently display QTc prolongation and complex ventricular arrhythmias, 4,6,25 anti-Ro/SSA are also silently present in a significant proportion of asymptomatic subjects of the general population. [8][9][10][11][12] An emblematic case of an anti-Ro/ SSA-associated TdP in an apparently healthy young woman has been recently reported in which clear evidence of a direct mechanistic link between circulating anti-Ro/SSA and QTc prolongation was provided. 13 This raises the distinct possibility that anti-Ro/SSA may represent a previously unrecognized risk factor involved in patients developing TdP.…”

Section: Discussionmentioning

confidence: 99%

“…7 Several studies have demonstrated that anti-Ro/SSA are the most frequent autoantibodies found in the general population with a frequency ranging from 0.5% to 2.7%. [8][9][10] Notably, this rate increases to ≈15% when the laboratory method used is immuno-Western blotting. 11 Anti-Ro/SSA-positive subjects, are in most cases (2/3), completely asymptomatic for autoimmune diseases (ADs), 8 particularly when anti-Ro/SSA-52-kD positivity occurs alone.…”

mentioning

confidence: 99%

Arrhythmogenicity of Anti-Ro/SSA Antibodies in Patients With Torsades de Pointes

Lazzerini

Yue

Srivastava

et al. 2016

Circ: Arrhythmia and Electrophysiology

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Background— In patients with autoimmune disease, anti-Ro/SSA antibodies (anti-Ro/SSA) are responsible for a novel autoimmune-associated long-QT syndrome by targeting the hERG potassium channel and inhibiting the related current ( I Kr ). Because anti-Ro/SSA are also present in a significant proportion of healthy subjects and may be associated with torsades de pointes (TdP) arrhythmia, we tested the hypothesis that anti-Ro/SSA may represent a silent risk factor in patients developing TdP. Methods and Results— Twenty-five consecutive patients who experienced TdP were prospectively collected independent of ongoing therapies and concomitant diseases. Anti-Ro/SSA were detected by fluoroenzyme immunoassay, immuno–Western blotting, and line-blot immunoassay. Purified IgGs from anti-Ro/SSA-positive and anti-Ro/SSA-negative patients were tested on I Kr using HEK293 cells stably expressing the hERG channel. As expected, in TdP patients, many known corrected QT interval–prolonging risk factors were simultaneously present, including hypokalemia that was the most common (52%). Anti-Ro/SSA were present in 60% of the subjects, mostly the anti-Ro/SSA-52-kD subtype detected by immuno–Western blotting only. A history of autoimmune disease was found in only 2 of anti-Ro/SSA-positive patients. Experimental data demonstrated that purified anti-Ro/SSA-positive IgGs significantly inhibited I Kr and cross reacted with hERG-channel proteins. Moreover, anti-Ro/SSA-positive sera exhibited high reactivity with a peptide corresponding to the hERG-channel pore-forming region. Conclusions— Anti-Ro/SSA may represent a clinically silent novel risk factor for TdP development via an autoimmune-mediated electrophysiological interference with the hERG channel. We propose that TdP patients may benefit from specific anti-Ro/SSA testing even in the absence of autoimmune diseases as immunomodulating therapies may be effective in shortening corrected QT interval and reducing TdP recurrence risk.

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The Prevalence of Antinuclear Antibodies in the General Population of China: A Cross-Sectional Study

Cited by 78 publications

References 18 publications

Individual and stable autoantibody repertoires in healthy individuals

Individual and stable autoantibody repertoires in healthy individuals

Associations of gender and a proxy of female menopausal status with histological features of drug‐induced liver injury

Arrhythmogenicity of Anti-Ro/SSA Antibodies in Patients With Torsades de Pointes

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