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1.
J Card Fail ; 25(4): 301-306, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30630065

ABSTRACT

BACKGROUND: Left ventricular assist devices (LVADs) can serve as a bridge to transplant or destination therapy for patients with advanced heart failure. Implantation of LVADs is known to be associated with increases in anti-HLA antibodies, but less is known about how autoantibody levels change with the use of these devices. METHODS AND RESULTS: Autoantibody levels were quantified with the use of customized antigen microarrays in 22 patients both before and after LVAD. We observed an increase (1.5- to 2-fold) in 14 IgG autoantibodies in the serum of patients after LVAD, including autoantibodies against cardiac proteins (myosin, troponin I, tropomyosin), DNA, and structural proteins (collagen, laminin). There was also a small but significant rise in total serum IgG after LVAD. Increases in autoantibodies after LVAD were positively associated with increases in calculated panel-reactive antibody class II (P = .05) and negatively correlated with age (r = -0.45; P < .05). Cytokines were evaluated to gain insights into the mechanism of antibody generation, and we observed a positive correlation between total IgG levels after LVAD and the level of monocyte chemoattractant protein 1 (r = 0.60; P < .05). CONCLUSIONS: LVAD implantation is associated with increases in IgG autoantibodies, anti-HLA antibodies, and total IgG. Increases in IgG after LVAD implantation may relate to an inflammatory response triggered by these devices.


Subject(s)
Autoantibodies/blood , Heart Failure/therapy , Heart Ventricles/physiopathology , Heart-Assist Devices/adverse effects , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , HLA Antigens/immunology , Heart Failure/blood , Heart Failure/physiopathology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Ventricular Function, Left/physiology
2.
PLoS One ; 11(3): e0151224, 2016.
Article in English | MEDLINE | ID: mdl-26967734

ABSTRACT

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR.


Subject(s)
Antigens/immunology , Autoantibodies/blood , Heart Failure/therapy , Heart Transplantation , Protein Array Analysis , Adult , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antigens/blood , Enzyme-Linked Immunosorbent Assay , Female , Graft Rejection/immunology , Heart Failure/immunology , Heart Failure/pathology , Humans , Immunoglobulin G/blood , Male , Middle Aged , Phenotype , Risk Factors
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