Calculated globulin (total protein - albumin) is usually tested as part of a liver function test profile in both primary and secondary care and determines the serum globulin concentration, of which immunoglobulins are a major component. The main use hitherto of calculated globulin is to detect paraproteins when the level is high. This study investigated the potential to use low levels of calculated globulin to detect antibody deficiency. Serum samples with calculated globulin cut-off < 18 g/l based on results of a pilot study were collected from nine hospitals in Wales over a 12-month period. Anonymized request information was obtained and the samples tested for immunoglobulin levels, serum electrophoresis and, if appropriate, immunofixation. A method comparison for albumin measurement using bromocresol green and bromocresol purple was undertaken. Eighty-nine per cent (737 of 826) samples had an immunoglobulin (Ig)G level of < 6 g/l using the bromocresol green methodology with a cut-off of < 18 g/l, and 56% (459) had an IgG of < 4 g/l. Patients with both secondary and primary antibody deficiency were discovered and serum electrophoresis and immunofixation showed that 1·2% (10) had previously undetected small paraproteins associated with immune-paresis. Using bromocresol purple, 74% of samples had an IgG of < 6 g/l using a cut-off of < 23 g/l. Screening using calculated globulin with defined cut-off values detects both primary and secondary antibody deficiency and new paraproteins associated with immune-paresis. It is cheap, widely available and under-utilized. Antibody-deficient patients have been discovered using information from calculated globulin values, shortening diagnostic delay and time to treatment with immunoglobulin replacement therapy.
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http://dx.doi.org/10.1111/cei.12369 | DOI Listing |
Alzheimers Dement
December 2024
Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Background: Alzheimer's disease (AD) is the most common form of dementia, characterized by cognitive impairment and memory loss. Previous studies have demonstrated that plasminogen, a key molecule in the fibrinolytic system, is implicated in the pathophysiology of AD. However, it is yet unknown whether the relationship between blood plasminogen and AD is causal.
View Article and Find Full Text PDFBackground: Amyloid-plaque removal by monoclonal antibody therapies slows progression in symptomatic Alzheimer's disease (AD), but effects on preventing the onset of symptoms and dementia in asymptomatic people with amyloid plaques are unknown. We report the final primary and secondary outcomes of the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial to evaluate amyloid-plaque removal in delaying disease progression, including symptom onset, in symptomatic and asymptomatic dominantly inherited Alzheimer's disease (DIAD) individuals treated for up to a decade.
Method: This double-blind, phase 2/3 trial (2012-2019), followed by open-label extension (OLE), investigated varying gantenerumab doses up to 1500 mg subcutaneous q2 weeks [NCT01760005].
Alzheimers Dement
December 2024
Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Background: Amyloid PET imaging enables the simultaneous assessment of both perfusion and amyloid deposition in people with Alzheimer's Disease (AD) in a single procedure. Perfusion can be derived from kinetic modeling of the full dynamic PET acquisition (i.e.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: Evidence suggests that a history of reduced estrogen exposure associates with greater Alzheimer's disease (AD) risk. However, the association of sex hormone levels with AD biomarkers has not been studied. We examined plasma levels of sex hormones in males and females with autosomal dominant AD due to the E280A Presenilin-1 mutation and age-matched non-carriers, and their relationship to AD brain pathology.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Background: In autosomal dominant Alzheimer disease (ADAD), the position of a pathogenic genetic variant within the presenilin-1 (PSEN1) coding sequence influences how amyloid-beta accumulates and how dementia progresses (Joseph-Mathurin et al, 2024). In the first trial of anti-amyloid monoclonal antibodies in individuals at risk for ADAD (Dominantly Inherited Alzheimer Network Trials Unit study 1 [DIAN-TU-001]), gantenerumab demonstrated target engagement but did not meet its primary clinical endpoint (Salloway et al, 2021). Whether the distribution of pathogenic genetic variants within the cohort may have influenced the trial results remains unclear.
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