7 research outputs found
Details of patient demographics, genotype and immune tolerance induction (ITI) regimen.
*<p>Patient 7 died at the age of 15 months (48 weeks into ERT); mo-months; IVIG-intravenous immunoglobulin.</p
ITI treatment regimen which includes rituximab, methotrexate and intravenous immunoglobulin (IVIG).
<p>This short course of ITI regimen (5 weeks) needs to be started together with the first dose of ERT. IVIG is administered on a monthly basis for a period of 5–6 months.</p
Representative Western gel blot showing CRIM negative status of four patients (lanes 3–6).
<p>Lane 1- protein magic marker; lane 8 -CRIM negative control cell line; lane 10 - normal human fibroblast (NHF) control; Lanes 2, 7 and 9 - left empty. 20 ug of skin fibroblast cell protein extract was loaded for each patient lane and 2.5 ug protein was loaded for NHF. Western blot was probed with anti-GAA antibody and ß-Actin was used as a protein loading control.</p
An algorithm for the management of cross-reactive immunologic material (CRIM)-negative (CN) infantile Pompe disease patients.
<p><sup>*</sup>Institutional review board (IRB) approved study (NCT01665326; <a href="http://www.clinicaltrials.gov" target="_blank">www.clinicaltrials.gov</a>) for rapid determination of CRIM status and long-term follow-up of response to treatment and ITI in Pompe disease. <sup>†</sup>CN status determination from an established CRIM negative mutation database, which allows prediction of CN status in more than 90% cases <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone.0067052-Bali1" target="_blank">[15]</a>. <sup>‡</sup>ITI regimen is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone-0067052-g002" target="_blank">Figure 2</a>. <sup>§</sup>Based on the literature antibody titers sustained at ≥6,400 results in a suboptimal therapeutic response to ERT. For that reason, 6,400 was used a cutoff for further intervention <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone.0067052-Banugaria1" target="_blank">[9]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone.0067052-Abbott1" target="_blank">[19]</a>. **Based on the half-life of rituximab, CD19% recovery is typically noted around 5 months. <sup>††</sup>The decision to repeat the same ITI regimen (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone-0067052-g003" target="_blank">figure 3</a>) or to administer ITI with a plasma-cell-targeting agent <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone.0067052-Banugaria4" target="_blank">[20]</a> should be based on multiple factors including, but not limited to, patients clinical status, CD19% and Fc<sub>γ</sub> receptor polymorphism. <sup>‡‡</sup>ITI regimen with plasma cell targeting agent such as bortezomib has been described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067052#pone.0067052-Banugaria4" target="_blank">[20]</a>.</p
Comparison of median left ventricular mass index (LVMI) values seen over time in CRIM-negative (CN) ERT monotherapy (n = 11) versus CN ERT+ITI (n = 7) treated patients.
<p>The upper limit of normal LVMI is 64 g/m<sup>2</sup> (represented by a horizontal dashed line).</p
Kaplan-Meier survival curve showing comparison of ventilator-free survival CRIM-negative (CN) ERT monotherapy (n = 11) versus CN ERT+ITI (n = 7) treated patients.
<p>*Three patients in the CN ERT+ITI group began the study invasively ventilated, became ventilator-free with treatment, and are currently still alive and ventilator-free. In contrast, all CN patients in ERT monotherapy treated group were invasive ventilator-free at baseline. This observation suggests that in some cases ERT+ITI can even reverse ventilator dependence in CN Pompe patients.</p