Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma

AIM To determine the prevalence and diagnostic value of autoantibodies inα-fetoprotein(AFP)-negative hepatocellular carcinoma(HCC).METHODS Fifty-six serum samples from AFP-negative HCC cases,86 from AFP-positive HCC cases,168 from chronic liver disease cases,and 59 from normal human controls were included in this study.Autoantibodies to nucleophosmin(NPM)1,14-3-3zeta and mouse double minute 2 homolog(MDM2)proteins in AFP-negative HCC serum were evaluated by enzymelinked im munosorbent assay.Partially positive sera were further evaluated by western blotting.Immunohistochemistry was used to detect the expression of three tumor-associated antigens(TAAs)in AFP-negative HCC and normal control tissues.RESULTS The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%,19.6%and 19.6%,which was significantly higher than in the chronic liver disease cases and normal human controls(P<0.01)as well as AFP-positive HCC cases.The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6%to 21.4%,and the specificity was approximately 95%.When the three autoantibodies were combined,the sensitivity reached 30.4%and the specificity reached 91.6%.CONCLUSION Autoantibodies to NPM1,14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

Evaluating Anti-SmDl-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases

Background： SmD1-amino-acid 83-119 peptide （SmD183-119） is the major epitope of Smith （Sm） antigen, which is specific for adult systemic lupus erythematosus （SLE）. The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119 antibodies remains unclear in children with SLE （cSLE）. This study aimed to assess the characteristics of anti-StuD 183-119 antibody in the diagnosis of cSLE. Methods： Samples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases （SLE [n = 46] and ankylosing spondylitis [AS, n = 11]）, nonautoimmune diseases （Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]） were collected from Shanghai Children＇s Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients＇ sera were analyzed for the anti-SmD 183-119, anti-Sm, anti-U 1-nRNP, anti-double-stranded DNA （dsDNA）, anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119 and other auto-antibodies were analyzed using the Spearman＇s correlation analysis. A value of P 〈 0.05 was considered statistically significant. Results： Thirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-StuD 183-119 had a higher sensitivity （78.3% vs. 26.1%, 2＇2 = 25.1, P 〈 0.05） and a lower specificity （90.8% vs. 100%, x^2 = 13.6, P 〈 0.05） in the diagnosis of cSLE. Further analysis revealed that anti-StuD 183-119 antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria. Conclusions： Measurement of anti-SmD183-119 in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sin. It has been suggested that inclusion of anti-SmD183-119 testing in the integrated laboratory diagnosis ofcSLE may significantly improve the overall sensitivity in child populations.