Article

Circulating cardiac troponin-I autoantibodies in human plasma and serum.

Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, Illinois 60064-6016, USA.
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 09/2009; 1173:67-74. DOI:10.1111/j.1749-6632.2009.04617.x
Source: PubMed

ABSTRACT We identified IgG reactive with human cardiac troponin-I (cTnI) in plasma and serum samples (N = 1930) from normal blood donors, and in sample cohorts characterized on the basis of clinical biomarkers associated with cardiac, infectious, and autoimmune diseases. cTnI and brain natriuretic peptide were the biomarkers chosen to reflect myocyte damage or left ventricular dysfunction, respectively. The infectious disease cohorts were serologically positive for antibodies to hepatitis B (natural infection), hepatitis C virus, and Chagas (i.e., T.cruzi). The autoimmune cohorts were represented by samples from diagnosed systemic lupus erythematosus (biomarker: dsDNA) and rheumatoid arthritis (biomarker: rheumatoid factor) subjects. The prevalence of IgG autoantibodies reactive with cTnI was high in the normal donor cohort (95/750, 12.7%). The prevalence in the other sample cohorts was not significantly different from that in the normal blood donors, with the exception of a slight increase in the rheumatoid factor cohort (28/137, 20.4%). The presence of anti-cTnI IgG in highly reactive samples was confirmed by inhibition with the antigen and further by screening with a library of peptides derived from the human cTnI amino acid sequence. Our data suggest that these autoantibodies are polyspecific, encompassing epitopes across the entire cTnI sequence, including the cardiac-specific amino terminal region.

0 0
 · 
0 Bookmarks
 · 
40 Views
  • [show abstract] [hide abstract]
    ABSTRACT: Heterophilic antibodies, comprising both "true" heterophilic antibodies and human anti-mouse antibodies (HAMA), represent an important source of interference in laboratory medicine, thus including cardiospecific troponin(s) testing. We describe the case of a 76-years-old women with implausible and persistent elevation of cardiospecific troponin I, which was finally attributed to interference from heterophilic antibodies. According to literature data, the frequency of this interference ranges between 0.1 and 3.1%, is almost unpredictable and unsuspected, may involve both cardiospecific troponin I and T, and may virtually affect any type of immunoassay, either one- or two-step. The presence of interfering antibodies should always be suspected when test results do not go hand in hand with the clinics, or with results of additional radiological and laboratory investigations. Once other causes of interference have been ruled out, test repetition with an alternative assay and removal of interfering antibodies with heterophilic antibodies blocking reagent, normal mouse serum, immobilized protein A column or polyethylene glycol may be advisable. As a simple alternative, measurement of serial dilutions of suspected samples usually shows nonlinearity of test results in the presence of heterophilic antibodies.
    Clinica chimica acta; international journal of clinical chemistry 09/2013; · 2.54 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA), are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease.
    PLoS Neglected Tropical Diseases 01/2014; 8(1):e2650. · 4.57 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Autoantibody against interferon is associated in many viral and non-viral diseases. This study aimed to determine the prevalence of anti-IFN-alpha autoantibodies in healthy Egyptian blood donors. The study included 558 (100 females (17.92%) and 458 males (82.08%)) Egyptian healthy blood donors who showed normal levels of liver enzymes and kidney tests and were conformed negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs, anti-HBc and Treponema Abs. Autoantibody against IFN-alpha-1a and IFN-alpha-2b were screened using ELISA. Anti-IFN-alpha-1a positive cases were found to be 43 subject (7.76%; 6 females (1.08%); 37 males (6.68%)) and anti-IFN-alpha-2b positive cases were found to be 3 (0.54%; all males). Combined positivity against both IFN-alpha-1a and IFN-alpha-2b was 38 (6.86%; 7 females (1.26%) and 31 males (6.60%)). From these findings we can conclude that antibodies against IFN-alpha are present in considerable number at low titer in accepted blood donors.
    Cellular Immunology 08/2011; 271(2):365-70. · 1.74 Impact Factor