CLN - The Sample
A new Duffy-null-adjusted absolute neutrophil count (ANC) reference range may reduce the proportion of individuals classified as abnormal, according to recent research (J Appl Lab Med 2026; doi.org/10.1093/jalm/jfag056).
The Duffy-null variant, rs281477 on the ACKR1/DARC gene, causes a below-normal concentration of neutrophils for lab results. Approximately 60–65% of African Americans and 4% of Middle Eastern people have this genotype. If Duffy-null patients take methotrexate or azathioprine, they likely will be misdiagnosed with drug-induced neutropenia.
To evaluate the change in ANC among individuals with the Duffy-null genotype who take either drug, the researchers analyzed All of Us cohort data from 91 patients on methotrexate and 35 on azathioprine. The researchers also considered the designation of normal versus abnormal ANC under genotype-adjusted and unadjusted thresholds by using data from the UK Biobank. The primary outcome was the log-mean difference in ANC between 1 year before and 2 years after starting medication. The secondary outcome was odds of having normal ANC under genotype-adjusted versus unadjusted thresholds.
Among azathioprine users, those with the Duffy-null genotype showed statistically insignificant lower ANC. Among methotrexate users, those with the genotype demonstrated a statistically significant lower ANC, with a log-mean difference of -0.042. Evaluation of unadjusted ANC thresholds in azathioprine patients revealed that Duffy-null genotype patients’ neutrophil counts were more likely to be abnormal (an odds ratio [OR] of 7.51; 95% CI, 1.64–34.43). Methotrexate users presented similar results (OR 4.35; 95% CI, 1.48–12.79). But under Duffy-adjusted thresholds, there were no significant differences between the genotypes in groups of people treated with either drug, according to the researchers.
The Duffy-adjusted absolute neutrophil count ANC reference range might help tens of millions of Americans by reducing unnecessary treatment interruptions, improving access to immunosuppressive therapy, and promoting more equitable clinical care, the researchers wrote.
Concentrations of plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) should be interpreted in the context of an individual’s demographic and physiological profile, recent research suggests (AMA Network Open 2026; doi: 10.1001/jamanetworkopen.2026.12793).
Previous research has shown changes in NfL and GFAP blood concentrations across a wide spectrum of neurological diseases, including preclinical and clinical Alzheimer’s disease (AD), and after acute neurological trauma and cerebrovascular insults. Other studies have shown a strong association between NfL and age, as patients develop comorbidities.
To address the lack of NfL and GFAP reference ranges that account for age-related comorbidities, the researchers aimed to determine the association of age, sex, kidney function via estimated glomerular filtration rate (eGFR), and body mass index (BMI) with GFAP and NfL concentrations in a healthy population. They conducted a cross-sectional study including 7,989 individuals ages 30–90 with no cognitive impairment to generate and validate reference intervals. A comparison group included patients with subjective cognitive decline or mild cognitive impairment due to AD, AD dementia, frontotemporal dementia (FTD), dementia with Lewy bodies, vascular dementia (VaD), or multiple sclerosis. The researchers measured and quantified plasma NfL and GFAP reference intervals, defined over age and adjusted for sex, BMI, and eGFR.
The results showed that older age, lower BMI, and reduced kidney function were associated with increased plasma NfL and GFAP concentrations. Female sex was associated with increased GFAP concentrations. Median NfL and GFAP concentrations were 6.58 pg/mL and 23.4 pg/mL higher, respectively, in participants with severe kidney damage, compared with those with no kidney damage. Median NfL and GFAP concentrations were 1.72 pg/mL and 12.6 pg/mL lower, respectively, in participants with obesity compared with those with average weight. Median NfL and GFAP concentrations were 1.72 pg/mL higher in females, compared with males. NfL concentrations were most elevated in participants with FTD, with 92.5% having concentrations greater than the median. More than 91% of participants with VaD had NfL concentrations greater than the median. GFAP concentrations were most elevated in participants with AD dementia, among whom 82.7% had concentrations greater than the median.
To determine GFAP or NfL elevation in the context of patients’ unique profiles, researchers developed a user-friendly web interface that allows clinicians to enter a patient’s GFAP or NfL concentrations with age, sex, BMI, and eGFR to get a corresponding percentile estimate.
A urine screening test may help identify children ages 2–11 at risk for autism spectrum disorder (ASD) (Mol Psychiatry 2026; doi: 10.1038/s41380-026-03620-5), the researchers said.
The test may flag autism sooner than current assessments, thereby driving earlier diagnosis and better long-term outcomes, the researchers said.
Previous research found that a subset of children with ASD have unusually high urinary concentrations of microbially-derived metabolites (MDMs), such as p-cresol sulfate and indoxyl sulfate. The researchers hypothesized that these MDMs may affect neurodevelopment through the gut-brain axis and that most children with ASD have an imbalance in the microorganisms of the digestive tract. Using semiquantitative liquid chromatography and mass spectrometry (LC-MS), followed by targeted quantitative LC-MS, researchers measured concentrations of many MDMs in the urine of 52 children with ASD and 47 healthy, typically developing (TD) children ages 2–11 years.
Some of the microbial metabolites elevated in the ASD children — such as indole-3-acetonitrile and indole 3-acetoxidoximide — had not been measured previously in ASD. A total of 23 MDMs were statistically higher in ASD children compared with children without ASD. Almost all children with ASD had one or more MDMs at concentrations above any TD child, and sometimes 100–1,000 times higher. These metabolites included phenylalanine-derived, tryptophan-derived, and yeast-derived MDMs. On average, children with ASD had three MDMs at levels above any TD child.
Classification using one or more elevated MDMs yielded a sensitivity of 90% and a specificity of 100%, according to the researchers. These data also suggest that approximately 90% of children with ASD have a distinct phenotype of ASD defined by quantitative lab measurements in urine.
The researchers said they are validating their testing system in another cohort.