A proof-of-principle study shows that blood-based targeted mass spectrometry (MS) is a feasible, patient-friendly alternative to detecting minimum residual disease (MRD) in multiple myeloma (MM) patients’ bone marrow via next-generation sequencing (NGS) (Clin Chem 2021; doi: 10.1093/clinchem/hvab187).
More than 50% of newly MM diagnosed patients reach a stringent complete response, but most of them relapse. This situation points to a need for new assays that can identify responses beyond conventionally defined stringent complete response. M-protein diagnostics are reliable, fast, and inexpensive but lack the sensitivity to detect low concentrations. Meanwhile, blood-based MS that targets M-protein-specific peptides has recently been introduced as a sensitive and minimally invasive alternative for MRD evaluation performed on bone marrow.
The researchers evaluated the feasibility of a MS-MRD assay in a cohort of 123 sera obtained from 41 multiple myeloma patients with results from serum protein electrophoresis, immunofixation electrophoresis, free light chain analysis, NGS-MRD, and a median of 51 months clinical follow-up. The researchers compared blood-based MS-MRD performance to conventional M-protein diagnostics and NGS-MRD evaluation performed on bone marrow. They found that MS-MRD is significantly more sensitive for detecting M-protein, compared to either electrophoretic M-protein diagnostics or serum free light chain analysis. The concordance between NGS-MRD and MS-MRD status in 81 paired bone marrow/sera samples was 79%. The 50% progression-free survival (PFD) was 49 months for patients who were NGS-positive or MS-positive directly after maintenance treatment. The 50% PFS rate was 69 and 89 months for NGS-negative and MS-negative patients, respectively. The longest 50% PFS—96 months—was observed in patients who were MRD-negative for both methods. MS-MRD relapse during maintenance treatment was significantly correlated to poor PFS, the researchers note.
The researchers anticipate that MS will not replace existing MRD bone marrow tests but will be a valuable companion method for longitudinal monitoring of MRD in blood.
Some Africans with Elevated Uric Acid Levels May Benefit from Kidney Dysfunction Screening
Sub-Saharan African patients with elevated serum uric acid (SUA) levels may benefit from periodic screening for kidney microvascular dysfunction, according to a recent study (JAMA Network Open 2021; doi:10.1001/jamanetworkopen. 2021.28985).
The cross-sectional study among a sub-Saharan African population found that elevated SUA levels were significantly associated with kidney microvascular dysfunction and mediated partly through high blood pressure.
The researchers did the study because previous research on the role of SUA levels in pathogenesis of microvascular and macrovascular dysfunction has typically excluded populations with sub Saharan African ancestry.
To determine associations of SUA levels with macrovascular and kidney microvascular dysfunction and evaluation factors that could mediate associations, the researchers performed a cross-section analysis of baseline data from 4,919 Ghanaian individuals living in Ghana and Europe. They used logistic regression to examine associations of SUA level quartiles with microvascular dysfunction (albuminuria) and macrovascular dysfunction (peripheral artery disease and coronary artery disease), with adjustments for age, sex, estimated glomerular filtration rate, site of residence, socioeconomic status, smoking, alcohol use, diabetes, waist-hip ratio, and total cholesterol level. The researchers also performed mediation analysis to assess whether associations were via elevated blood pressure, hemoglobin A1c, and high-sensitivity C-reactive protein levels or via weight-hip ratio. The research questions were formulated after data collection.
The researchers found a significant positive association between SUA quartiles and albuminuria, but not coronary artery disease or peripheral artery disease, after adjustment for covariates. After full adjustment, individuals in the fourth SUA quartile had higher odds of albuminuria (adjusted odds ratio [aOR], 1.54; 95% CI, 1.07-2.21), but not peripheral artery disease (aOR, 1.35; 95% CI, 0.87-2.08) or coronary artery disease (aOR, 1.09; 95% CI, 0.77-1.55), compared with individuals in the first quartile. After full adjustment, systolic and diastolic blood pressure significantly mediated the association between SUA concentrations and albuminuria, accounting for 19.4% of the total association for systolic blood pressure and 17.2% for diastolic blood pressure. Hemoglobin A1c, high-sensitivity C-reactive protein, and waist-hip ratio did not mediate this association.
Noting substantial genetic diversity in African populations, the researchers call for studies to replicate their findings in other sub-Saharan populations, especially those in Eastern and Southern Africa.Protein Detectable in Nasopharyngeal Sample May Indicate Serious COVID-19
Analysis of a cell surface protein likely predicts who is in danger of a serious infection caused by SARS-CoV-2. The protein, hFweLose, accurately predicts outcomes in COVID-19 patients, according to a recent paper (EMBO Mol Med 2021; doi: 10.15252/emmm.202013714).
hFweLose gene expression in the upper respiratory tract outperformed other prognostic factors such as patient age, comorbidities, and clinical markers of inflammation in predicting patient outcomes.
To evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting death and hospitalization in COVID19 patients, the researchers performed a postmortem examination of infected lung tissue in deceased COVID-19 patients to determine hFweLose’s biological role in acute lung injury.
Afterwards, the researchers performed an observational study involving 283 subjects to evaluate whether hFwe-Lose expression in nasopharyngeal samples could predict hospitalization or death in COVID-19 patients.
In patients presenting in the early phase of COVID-19 illness, hFwe-Lose expression accurately predicted subsequent hospitalization or death with positive predictive values of 87.8–100% and a negative predictive value of 64.1–93.2%. hFwe-Lose expression outperformed conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) of 0.93–0.97 in predicting hospitalization and death.
The researchers noted that this AUROC figure is significantly higher than the prognostic value of combining the biomarkers serum ferritin, D-dimer, C-reactive protein, and neutrophil-lymphocyte ratio, plus patient age and comorbidities. That method has an AUROC of 0.67–0.92.
The findings demonstrate how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID-19 pandemic, the researchers note. They add that nasopharyngeal samples for hFwe-Lose expression can be obtained when the patient first presents for SARS-CoV-2 testing in a variety of settings.