Dataset Information

Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies.

ABSTRACT: Background:Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries. Objective:The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD. Methods:CD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD. Results:Genetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5-6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported. Conclusion:Results of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD.

SUBMITTER: Blazina S

PROVIDER: S-EPMC5871747 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies.

Blazina Štefan Š Debeljak Maruša M Košnik Mitja M Simčič Saša S Stopinšek Sanja S Markelj Gašper G Toplak Nataša N Kopač Peter P Zakotnik Breda B Pokorn Marko M Avčin Tadej T

Frontiers in immunology 20180321

<h4>Background</h4>Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries.<h4>Objective</h4>The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD.<h4>Method ...[more]

PMID: 29619023

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Project description:Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.

Project description:BackgroundThere have been few longitudinal studies assessing the effect of preoperative phenotypic severity on long-term esthetic outcomes in metopic craniosynostosis. This study evaluates the relationship between metopic severity and long-term esthetic outcomes using interfrontal angle (IFA) and CranioRate, a novel metopic synostosis severity measure.MethodsPatients with metopic craniosynostosis who underwent bifrontal orbital advancement and remodeling between 2012 and 2017 were reviewed. Preoperative computed tomography head scans were analyzed for IFA and CranioRate, a machine learning algorithm which generates quantitative severity ratings including metopic severity score (MSS) and cranial morphology deviation (CMD). Long-term esthetic outcomes were assessed by craniofacial surgeons using blinded 3-rater esthetic grading of clinical photos. Raters assessed Whitaker score and the presence of temporal hollowing, lateral orbital retrusion, frontal bone irregularities and/or "any visible irregularities."ResultsPreoperative scans were performed at a mean age of 7.7±3.4 months, with average MSS of 6/10, CMD of 200/300, and IFA of 116.8±13.8 degrees. Patients underwent bifrontal orbital advancement and remodeling at mean 9.9±3.1 months. The average time from operation to esthetic assessment was 5.4±1.0 years. Pearson correlation revealed a significant negative correlation between MSS and age at computed tomography ( r =-0.451, P =0.004) and IFA ( r =-0.371, P =0.034) and between IFA and age at surgery ( r =-0.383, P =0.018). In multinomial logistic regression, preoperative MSS was the only independent predictor of visible irregularities (odds ratio=2.18, B =0.780, P =0.024) and preoperative IFA alone significantly predicted Whitaker score, with more acute IFA predicting worse Whitaker score (odds ratio=0.928, B =-0.074, P =0.928).ConclusionsMore severe preoperative phenotypes of metopic craniosynostosis were associated with worse esthetic dysmorphology. Objective measures of preoperative metopic severity predicted long-term esthetic outcomes.

Dataset Information

Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies.

Publications

Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies.

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