Multiple sclerosis and HLA genotypes: A possible influence on brain atrophy

2017 ◽  
Vol 25 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Lorena Lorefice ◽  
Giuseppe Fenu ◽  
Claudia Sardu ◽  
Jessica Frau ◽  
Giancarlo Coghe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
High Risk ◽  
Brain Atrophy ◽  
Group Versus ◽  
Brain Magnetic Resonance Imaging ◽  
Human Leukocyte ◽  
Low Risk ◽  
Brain Volume Loss ◽  
Hla Genotypes ◽  
Hla Genotype

Background: The strongest genetic determinant for multiple sclerosis (MS) is located at the human leukocyte antigen (HLA) class II DRB1 and DQB1 loci. Objectives: To investigate the possible role of predisposing HLA genotypes in determining brain atrophy. Methods: HLA genotypes were categorized as high risk (two predisposing haplotypes) or medium/low risk (one or no predisposing haplotypes). Patients underwent a brain magnetic resonance imaging (MRI) study and volumes of white matter (WM), gray matter (GM), and whole brain (WB) were estimated with SIENAX. Longitudinal atrophy was also assessed with SIENA. Results: The study included 240 MS patients. In 51/240 (21%) subjects, a high-risk HLA genotype was observed, while medium- and low-risk HLA genotypes were 109/240 (45%) and 80/240 (34%), respectively. Multiple regression analysis found that the high-risk HLA genotype was associated with significant reduction in WB ( p = 0.02) and GM ( p = 0.03) volumes compared with the medium-/low-risk HLA genotypes, independently from MS clinical features. The longitudinal study included 60 patients and showed a brain volume loss of −0.79% in high-risk HLA genotype group versus −0.56% in low-risk HLA genotype. Conclusion: Our results suggest an influence of HLA genotype on WB and GM atrophy. Further investigations are necessary to confirm these findings.

scholarly journals Exocrine pancreas function is impaired in adult relatives of patients with type 1 diabetes

2021 ◽  
Author(s):  
Anna Giovenzana ◽  
Federica Vecchio ◽  
Federica Cugnata ◽  
Alessandro Nonis ◽  
Alessandra Mandelli ◽  
...  
Keyword(s):  
At Risk ◽  
Type 1 Diabetes ◽  
High Risk ◽  
Exocrine Pancreas ◽  
Pancreatic Enzyme ◽  
Low Risk ◽  
C Peptide ◽  
Hla Genotypes ◽  
Pancreas Function

Abstract Aims Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes. Methods Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals). Linear mixed models were adopted to estimate variation of pancreatic enzymes among the groups and to evaluate the influence of high-risk HLA genotypes and residual beta cell function on exocrine pancreas function. Results In adults, but not children, reduced levels of P-amylase and lipase were shown in at-risk individuals, including (for P-amylase levels only) those at low-risk, and in T1Dnew. Furthermore, while high-risk HLA genotypes negatively affected P-amylase levels in autoantibody negative adult individuals, fasting C-peptide levels did not correlate with pancreatic enzyme levels. Conclusions Exocrine pancreas dysfunction precedes the onset of type 1 diabetes in adult at-risk individuals and may be unrelated to fasting C-peptide levels.

scholarly journals Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis

2019 ◽  
Vol 47 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Andreas P. Lysandropoulos ◽  
Gaetano Perrotta ◽  
Thibo Billiet ◽  
Annemie Ribbens ◽  
Renaud Du Pasquier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Visual Memory ◽  
Verbal Learning ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Lesion Volume ◽  
Leukocyte Antigen ◽  
Hla Genotype

ABSTRACT:Objective:In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.Methods:Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.Results:Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.Conclusion:In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

Real-Time Risk Tool for Pharmacy Interventions

2020 ◽  
pp. 001857872097388
Author(s):  
Hanh L. Nguyen ◽  
Kristin S. Alvarez ◽  
Boryana Manz ◽  
Arun Nethi ◽  
Varun Sharma ◽  
...  
Keyword(s):  
High Risk ◽  
Prediction Models ◽  
Risk Model ◽  
Hospital Readmissions ◽  
Group Versus ◽  
Safety Net ◽  
Low Risk ◽  
Day Hospital ◽  
Significant Difference ◽  
Safety Net Hospital

Background: Adverse drug events (ADEs) result in excess hospitalizations. Thorough admission medication histories (AMHs) may prevent ADEs; however, the resources required oftentimes outweigh what is available in large hospital settings. Previous risk prediction models embedded into the Electronic Medical Record (EMR) have been used at hospitals to aid in targeting delivery of scarce resources. Objective: To determine if an AMH scoring tool used to allocate resources can decrease 30-day hospital readmissions. Design, Setting, and Participants: Propensity-matched cohort study, Medicine/Surgery patients in large academic safety-net hospital. Intervention or Exposure: Pharmacy-conducted AMHs identified by risk model versus standard of care AMH. Main Outcomes and Measures: A total of 30-day hospital readmissions and inpatient ADE prevention. Results: The model screened 87 240 hospitalizations between June 2017 and June 2019 and 4027 patients per group were included. There were significantly less 30 day readmissions among high-risk identified patients that received a pharmacy-conducted AMH compared to controls (11% vs 15%; P = 0.004) and no significant difference in readmission rates for low-risk patients. While there was significantly higher documentation of major ADE prevention in the pharmacy-led AMH group versus control (1656 vs 12; P < 0.001), there was no difference in electronically-detected inpatient ADEs between groups. Conclusions: A risk tool embedded into the EMR can be used to identify patients whom pharmacy teams can easily target for AMHs. This study showed significant reductions in readmissions for patients identified as high-risk. However, the same benefit in readmissions was not seen in those identified at low-risk, which supports allocating resources to those that will benefit the most.

scholarly journals Prevalence of SARS-CoV-2 Antibodies in Multiple Sclerosis: The Hidden Part of the Iceberg

2020 ◽  
Vol 9 (12) ◽  
pp. 4066
Author(s):  
Nicola Capasso ◽  
Raffaele Palladino ◽  
Emma Montella ◽  
Francesca Pennino ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
High Risk ◽  
Cross Sectional Study ◽  
Low Risk ◽  
High Risk Population ◽  
Chi Square ◽  
Cross Sectional ◽  
Risk Population ◽  
Exact Test ◽  
Chi Square Test

Background. We compared the prevalence of SARS-CoV-2 IgG/IgM in multiple sclerosis (MS), low-risk, and high-risk populations and explored possible clinical correlates. Methods. In this cross-sectional study, we recruited MS patients, low-risk (university staff from non-clinical departments), and high-risk individuals (healthcare staff from COVID-19 wards) from 11 May to 15 June 2020. We used lateral flow immunoassay to detect SARS-CoV-2 IgG and IgM. We used t-test, Fisher’s exact test, chi square test, or McNemar’s test, as appropriate, to evaluate between-group differences. Results. We recruited 310 MS patients (42.3 ± 12.4 years; females 67.1%), 862 low-risk individuals (42.9 ± 13.3 years; females 47.8%), and 235 high-risk individuals (39.4 ± 10.9 years; females 54.5%). The prevalence of SARS-CoV-2 IgG/IgM in MS patients (n = 9, 2.9%) was significantly lower than in the high-risk population (n = 25, 10.6%) (p < 0.001), and similar to the low-risk population (n = 11, 1.3%) (p = 0.057); these results were also confirmed after random matching by age and sex (1:1:1). No significant differences were found in demographic, clinical, treatment, and laboratory features. Among MS patients positive to SARS-CoV-2 IgG/IgM (n = 9), only two patients retrospectively reported mild and short-lasting COVID-19 symptoms. Conclusions. MS patients have similar risk of SARS-CoV-2 infection to the general population, and can be asymptomatic from COVID-19, also if using treatments with systemic immunosuppression.

scholarly journals Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets

2017 ◽  
Vol 24 (2) ◽  
pp. 222-226 ◽  
Author(s):  
Nicola De Stefano ◽  
Antonio Giorgio ◽  
Marco Battaglini ◽  
Alessandro De Leucio ◽  
Christine Hicking ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Placebo Treatment ◽  
Cumulative Probability ◽  
Resonance Imaging ◽  
Disability Progression ◽  
Reliable Measure ◽  
Brain Volume Loss ◽  
Relapsing Multiple Sclerosis

Background: Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage. Methods: In the CLARITY study ( ClinicalTrials.gov NCT00213135), the effect of 2 years’ treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS). Results: Compared with placebo (–0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (–0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (–0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa. Conclusions: Cladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.

scholarly journals Clinical Performance Status and Technical Factors Affecting Outcomes from Percutaneous Transhepatic Biliary Interventions; A Multicentre, Prospective, Observational Cohort Study

2021 ◽  
Author(s):  
Gregory C. Makris ◽  
Andrew C. Macdonald ◽  
Kader Allouni ◽  
Hannah Corrigall ◽  
Charles R. Tapping ◽  
...  
Keyword(s):  
Cohort Study ◽  
High Risk ◽  
Risk Group ◽  
Performance Status ◽  
Group Versus ◽  
High Risk Group ◽  
Low Risk ◽  
Karnofsky Score ◽  
The Uk ◽  
Biliary Interventions

Abstract Purpose The purpose of this study was to evaluate the predictive value of a ‘Modified Karnofsky Scoring System’ on outcomes and provide real-world data regarding the UK practice of biliary interventions. Materials and Methods A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure. Results A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky ‘high risk’ group the 7 day mortality was 9.7% versus 0% for the ‘low risk’ group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) Conclusion Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.

Cognitive reserve moderates the negative effect of brain atrophy on cognitive efficiency in multiple sclerosis

2009 ◽  
Vol 15 (4) ◽  
pp. 606-612 ◽  
Author(s):  
JAMES F. SUMOWSKI ◽  
NANCY CHIARAVALLOTI ◽  
GLENN WYLIE ◽  
JOHN DELUCA
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Cognitive Reserve ◽  
Depressive Symptomatology ◽  
Third Ventricle ◽  
Brain Magnetic Resonance Imaging ◽  
Hierarchical Regression ◽  
Premorbid Intelligence ◽  
Negative Effect ◽  
Serial Addition

AbstractAccording to the cognitive reserve hypothesis, neuropsychological expression of brain disease is attenuated among persons with higher education or premorbid intelligence. The current research examined cognitive reserve in multiple sclerosis (MS) by investigating whether the negative effect of brain atrophy on information processing (IP) efficiency is moderated by premorbid intelligence. Thirty-eight persons with clinically definite MS completed a vocabulary-based estimate of premorbid intelligence (Wechsler Vocabulary) and a composite measure of IP efficiency (Symbol Digit Modalities Test and Paced Auditory Serial Addition Task). Brain atrophy was estimated from measurements of third ventricle width using high-resolution anatomical brain magnetic resonance imaging (magnetization-prepared rapid gradient echo). In a hierarchical regression analysis controlling for age and depressive symptomatology, brain atrophy predicted worse IP efficiency (R2 = .23, p = .003) and cognitive reserve predicted better IP efficiency (R2 = .13, p = .013), but these effects were moderated by an Atrophy × Cognitive Reserve interaction (R2 = .15, p = .004). The negative effect of brain atrophy on IP efficiency was attenuated at higher levels of reserve, such that MS subjects with higher reserve were better able to withstand MS neuropathology without suffering cognitive impairment. Results help explain the incomplete and inconsistent relationship between brain atrophy and IP efficiency in previous research. (JINS, 2009, 15, 606–612.)

scholarly journals Comparing longitudinal brain atrophy measurement techniques in a real-world multiple sclerosis clinical practice cohort: towards clinical integration?

2019 ◽  
Vol 12 ◽  
pp. 175628641882346 ◽  
Author(s):  
H.N. Beadnall ◽  
C. Wang ◽  
W. Van Hecke ◽  
A. Ribbens ◽  
T. Billiet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Real World ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Measurement Techniques ◽  
Intraclass Correlation ◽  
Three Dimensional ◽  
Statistical Correlation ◽  
Brain Volume Loss

Background: Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients. Methods: Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner. Three-dimensional (3D) T1-weighted and two-dimensional (2D)/3D fluid-attenuated inversion-recovery sequences were analysed. Percentage brain volume change (PBVC) measurements were calculated using SIENA and icobrain long. Statistical correlation, agreement and consistency between methods was evaluated; MRI brain volumetric and clinical data were compared. The proportion of the cohort with annualized brain volume loss (aBVL) rates ⩾ 0.4%, ⩾0.8% and ⩾0.94% were calculated. No evidence of disease activity (NEDA) 3 and NEDA 4 were also determined. Results: Mean annualized PBVC was −0.59 (±0.65)% and −0.64 (±0.73)% as measured by icobrain long and SIENA. icobrain long and SIENA-measured annualized PBVC correlated strongly, r = 0.805 ( p < 0.001), and the agreement [intraclass correlation coefficient (ICC) 0.800] and consistency (ICC 0.801) were excellent. Weak correlations were found between MRI metrics and Expanded Disability Status Scale scores. Over half the cohort had aBVL ⩾ 0.4%, approximately a third ⩾0.8%, and aBVL was ⩾0.94% in 28.43% and 23.53% using SIENA and icobrain long, respectively. NEDA 3 was achieved in 35.29%, and NEDA 4 in 15.69% and 16.67% of the cohort, using SIENA and icobrain long to derive PBVC, respectively. Discussion: icobrain long quantified longitudinal WBA with a strong level of statistical agreement and consistency compared to SIENA in this real-world MS population. Utility of WBA measures in individuals remains challenging, but show promise as biomarkers of neurodegeneration in MS clinical practice. Optimization of MRI analysis algorithms/techniques are needed to allow reliable use in individuals. Increased levels of automation will enable more rapid clinical translation.

scholarly journals Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 28
Author(s):  
Claudia M. Muñoz-Herrera ◽  
Juan Francisco Gutiérrez-Bautista ◽  
Miguel Ángel López-Nevot
Keyword(s):  
Kidney Transplantation ◽  
Graft Rejection ◽  
Human Leukocyte ◽  
Case Patient ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Leukocyte Antigens ◽  
Hla Genotypes ◽  
Donor Specific Antibodies ◽  
Hla Genotype

Kidney transplantation, like other transplants, has the risk of producing graft rejection due to genetic differences between donor and recipient. The three known types of renal rejection are listed in the Banff classification: T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mixed rejection. The human leukocyte antigens (HLA) are highly polymorphic and may be the targets of donor-specific antibodies, resulting in ABMR. Therefore, prior to transplantation, it is necessary to analyze the HLA genotype of the donor and recipient, as well as the presence of DSA, in order to avoid hyperacute rejection. However, due to the shortage of kidneys, it is very difficult to find a donor and a recipient with completely matched HLA genotypes. This can trigger a future rejection of the kidney, as is reported in this work. We describe a patient who received a kidney transplant after a negative DSA test, who developed graft rejection with antibodies against the donor’s HLA-Bw4 public epitope and lymphocytic infiltrate four days after transplantation, whose differential diagnosis was mixed rejection.

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