Early-Onset Cardiomyopathy After Pacemaker Implanted in a Preterm Infant With Congenital Complete Heart Block and Anti-Ro/SSA Antibodies.
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SUBMITTER: Iqbal M
PROVIDER: S-EPMC8262823 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundExperimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB).ObjectivesHydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB.MethodsThis multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash.ResultsBy intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4).ConclusionsThese prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573).
| S-EPMC7394202 | biostudies-literature
Project description:Anti-SSA/Ro antibodies are necessary but not sufficient to provoke autoimmune-associated congenital heart block (CHB). Genetic factors are likely contributory. Accordingly, HLA-related candidates and single-nucleotide polymorphisms in the promoter region of tumor necrosis factor ? and codon 10 in transforming growth factor ?1 (TGF?1) were evaluated in a unique family: the surrogate mother (anti-SSA/Ro positive), the biologic father, and the CHB-affected child (product of ovodonation). There was an HLA mismatch between the affected child and the surrogate mother. However, both the biologic and the surrogate mothers shared DQ2 and the profibrosing leucine polymorphism at codon 10 of TGF?. In conclusion, we observed that CHB can develop in a genetically unrelated child exposed in utero to anti-SSA/Ro antibodies. Testing for anti-SSA/Ro antibodies might be considered in women undergoing artificial fertilization. It is possible that there is no direct association of maternal genes beyond a contributory role in generating the autoantibody.
| S-EPMC3931307 | biostudies-literature
Project description:Isolated congenital atrioventricular block (CAVB) is a rare condition with multiple clinical outcomes. Ventricular remodeling can occur in approximately 10% of the patients after pacemaker (PM) implantation.To assess the functional capacity of children and young adults with isolated CAVB and chronic pacing of the right ventricle (RV) and evaluate its correlation with predictors of ventricular remodeling.This cross-sectional study used a cohort of patients with isolated CAVB and RV pacing for over a year. The subjects underwent clinical and echocardiographic evaluation. Functional capacity was assessed using the six-minute walk test. Chi-square test, Fisher's exact test, and Pearson correlation coefficient were used, considering a significance level of 5%.A total of 61 individuals were evaluated between March 2010 and December 2013, of which 67.2% were women, aged between 7 and 41 years, who were using PMs for 13.5 ± 6.3 years. The percentage of ventricular pacing was 97.9 ± 4.1%, and the duration of the paced QRS complex was 153.7 ± 19.1 ms. Majority of the subjects (95.1%) were asymptomatic and did not use any medication. The mean distance walked was 546.9 ± 76.2 meters and was strongly correlated with the predicted distance (r = 0.907, p = 0.001) but not with risk factors for ventricular remodeling. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0) CONCLUSIONS: The functional capacity of isolated CAVB patients with chronic RV pacing was satisfactory but did not correlate with risk factors for ventricular remodeling.
| S-EPMC4387613 | biostudies-literature
Project description:Complete heart block is a common complication for adults with congenital heart disease (CHD). Epicardial pacing is preferred in patients with septal shunting due to risk of thromboembolism. Anatomic changes in complex CHD may preclude surgical epicardial lead placement. Thromboembolism risk reduction in such patients requiring endocardial pacing remains questionable. (Level of Difficulty: Advanced.).
| S-EPMC8310934 | biostudies-literature
Project description:The 52 kDa Ro/SSA protein is an intracellular autoantigen that is frequently recognized by antibodies in sera of patients with systemic lupus erythematosus or Sjogren's syndrome. While the function of this molecule is not known, zinc finger and leucine zipper motifs have been identified in its predicted amino acid sequence which suggest that it may interact with nucleic acids. To test this hypothesis, the human gene which encodes this protein was cloned in a baculovirus and expressed in Spodoptera frugipoda cells. Extracts from these infected insect cells were used as a source of protein for this study. The protein is similar in size and antigenicity to that expressed in human cells. This protein binds to DNA at physiological temperature and is eluted with high concentrations of sodium chloride. Striking similarities were found between the sequence in, and adjacent to, the nucleic acid-binding motifs of 52 kDa Ro/SSA and a growing family of zinc finger proteins which have been shown to bind to DNA or regulate gene expression. The findings presented here place this protein structurally and functionally in this family and demonstrate a biochemical assay which can be used to study its function.
| S-EPMC1136368 | biostudies-other
Project description:Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. KEY MESSAGE:Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.
| S-EPMC5239802 | biostudies-other
Project description:BackgroundTo report first clinical experience on three cases of congenital complete heart block and the use of a pacemaker system with a maximum lower rate interval of 95 beats per minute.MethodsWe retrospectively analyzed three patients treated with a pacemaker system with a maximum lower rate interval of 95 beats per minute suffering from congenital complete heart block. We report a follow up period of 2.9 years, focusing on the patients' growth, development, and adverse events, as well as pacemaker function.ResultsIn all three patients pacemaker function was impeccable, including minute ventilation sensor rate adaption. All patients showed limited growths as expected, adequate development, good feeding tolerability and circadiane heart rate adaption. One patient experienced skin traction and revision. All patients showed high aortic velocity time integral values after birth.ConclusionThe use of a pacemaker system with a maximum lower rate interval of 95 beats per minute in infants suffering from congenital complete heart block and showing high aortic VTI values seems to be feasible and to result in limited growths but adequate development.
| S-EPMC6480703 | biostudies-literature
Project description:The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients-health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren's syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.
| S-EPMC7600347 | biostudies-literature
Project description:ObjectivesTo determine the diagnostic potential of simultaneous presence of serum anti-SSA/Ro and upregulated salivary protein biomarkers in patients with primary Sjögren's syndrome (pSS).MethodsPrevious proteomics data on the intensity of neutrophil elastase, calreticulin, tripartite motif containing protein 29 (TRIM29), clusterin and vitronectin provided basis for performing extended analysis. Protein data was obtained by liquid chromatography tandem mass spectrometry technique in whole saliva from 24 patients with pSS and 16 patients having symptoms of pSS, but not fulfilling the American College of Rheumatology/European League against Rheumatism classification criteria (non-pSS). Serum anti-SSA/Ro antibody was measured using enzyme-linked immunosorbent assays. Receiver operating characteristic curve (ROC) value was calculated for combined biomarkers.ResultsSimultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided the most optimal combination with an area under curve (AUC) of 0.995 (95% CI 0.98-1.00, p = 2.0E-7 and standard error 0.007) and combinations of sensitivity and specificity within the interval of 91-100%. ROC analysis showed that salivary levels of TRIM29 alone enabled differentiation between pSS and non-pSS with an area under curve (AUC) of 0.88 (95%CI 0.77-1.00). All patients with pSS and 3 non-pSS patients were serum anti-SSA/Ro positive.ConclusionsSimultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided a high diagnostic accuracy exceeding that of currently available tools used in pSS diagnostics. This biomarker combination represents a promising less invasive diagnostic tool for pSS. The clinical applicability of TRIM29 needs further testing in independent cohorts using relevant analytical techniques.
| S-EPMC8500413 | biostudies-literature
Project description:Development of the gut microbiota is greatly impacted in preterm infants. Despite increasing knowledge about microbiota composition in preterm infants, knowledge about the functional signatures of the intestinal microbiota remains limited. The aim was to study transitions in microbiota activity during the first six postnatal weeks in ten preterm infants. A total of 64 stool samples were measured by LC-MS/MS.
2017-07-14 | PXD005574 | Pride