| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Al-Rabadi, Laith Farah, et al.
(författare)
-
Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy
- 2021
-
Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology (ASN). - 1046-6673 .- 1533-3450. ; 32:7, s. 1666-1681
-
Tidskriftsartikel (refereegranskat)abstract
- Background Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. Methods A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. Results These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. Conclusions Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.
|
|
| 3. |
- Perera, G, et al.
(författare)
-
Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records
- 2020
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:11, s. e038753-
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations.DesignCase–control study.SettingSix European electronic health records databases.Participants291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date.ExposureThe following measures were extracted whenever recorded within each dataset: BMI (kg/m2), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date.Main outcomesCase–control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases.ResultsMean BMI (coefficient −1.16 kg/m2; 95% CI –1.38 to 0.93) and SBP (−2.83 mm Hg; 95% CI –4.49 to –1.16) were lower in cases at diagnosis, and case–control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant.ConclusionRoutine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.
|
|
| 4. |
- Rubinstein, Yaffa R., et al.
(författare)
-
The case for open science : rare diseases
- 2020
-
Ingår i: JAMIA Open. - : Oxford University Press (OUP). - 2574-2531. ; 3:3, s. 472-486
-
Forskningsöversikt (refereegranskat)abstract
- The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally.
|
|
