Preimmunosuppression serologic testing questioned

A recent study suggests that the current use of hepatitis B (HepB) and varicella serology in children may be inappropriate because of rapid waning of titers (Clinical Chemistry 2025; doi: 10.1093/clinchem/hvaf020).

The researchers suggest that applying age-appropriate reference intervals to vaccine serologic tests will provide a foundation for improved treatment recommendations and standards of care.

Certain clinical situations may warrant antibody response testing in children. These include starting lifelong immunosuppression following organ transplant or treatment of autoimmune diseases, or confirming vaccination for children without related records. Meanwhile, many children with autoimmune diseases have inadequate vaccine-induced immunity at the time of presentation.

The period prior to starting immune suppression serves as the critical window for giving pediatric patients live vaccines if they do not have adequate preexisting immunity. However, age-appropriate thresholds for antibody levels have not yet been established for children. Decisions to revaccinate are based on thresholds derived from adult studies, which may overestimate durable immunity in young children because of expected titer waning as the time from vaccination increases.

In response, the researchers aimed to investigate age-specific differences in antibody levels in healthy children to guide determinations of vaccine immunity status when clinically indicated.

The researchers conducted a cross-sectional study that assessed clinical serology for measles, mumps, rubella (MMR), varicella, and HepB in an age-stratified cohort of healthy children ages 1-18 who were current on their vaccinations. Using a total of 471 remnant samples from 471 children, the study assessed clinical serology for the viruses.

Children of all ages had detectable titers to MMR, but median titers for HepB and varicella waned by ages 11-12 and 9-10 years, respectively. Children had titers above adult thresholds for MMR at all measured timepoints, retrospectively resulting in 24.6% (95% CI, 21.6%-27.8%) of children having an inappropriate MMR classification with the use of adult thresholds instead of pediatric ones.

Application of age-appropriate reference intervals for vaccine serologic tests will drive improved treatment recommendations and standards of care, the paper said. It also calls for research on age-appropriate cutoffs for other common vaccinations, including diphtheria, tetanus, pertussis, Haemophilus influenzae, and pneumococcus.

STUDY HIGHLIGHTS NEED FOR GENOMIC TESTING IN METASTATIC PROSTATE CANCER

Recent findings reinforce the utility of genomic testing to find metastatic prostate cancer (mPCa) patients with treatable genetic variations, with the goal of achieving more equitable outcomes among different racial and ethnic groups (JAMA Network Open 2025; doi:10.1001/jamanetworkopen.2025.9119).

National guidelines recommend next-generation sequencing of tumors in patients diagnosed with mPCa to identify potentially actionable genetic variations. Because non-Hispanic Black men are poorly represented in precision oncology cohorts, the differences in variation frequencies between non-Hispanic Black and White men remain poorly characterized.

In response, the researchers performed a cohort study to compare frequency of actionable and inactionable genetic variations between non-Hispanic Black and non-Hispanic White United States veterans with mPCa, and to better understand how the variations affect survival.

Of 5,015 veterans, 35.6% were non-Hispanic Black men at a mean age of 64.4, and 64.4% were non-Hispanic White men at a mean age of 67.4. Non-Hispanic Black veterans were younger, had higher prostate-specific antigen levels at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared with non-Hispanic White veterans.

The researchers found that 9 out of 10 of the most commonly altered genes were the same in non-Hispanic Black and non-Hispanic White veterans, but the frequencies of alterations varied by race and ethnicity. Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% CI, 1.2-2.6) and immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5), including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4). Non-Hispanic Black race and ethnicity was also associated with lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8).

Analysis that involved stratifying by race and ethnicity found that alterations in tumor suppressor genes, including TP53, were associated with shorter overall survival in both non-Hispanic Black (hazards ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.

APOLIPOPROTEIN B AND LIPOPROTEIN(A) INDICATE ATHEROSCLEROTIC RISK

Measuring both apolipoprotein B particles (apoB-P) and lipoprotein a ([Lp(a)]) is best for assessing blood lipids for atherosclerotic risk, recent research shows (European Heart Journal 2025; doi.org/10.1093/eurheartj/ehaf207).

ApoB-P concentration reflects the number of atherogenic lipoproteins and is widely recognized as a key lipid risk marker. However, whether the type or size of ApoB-P adds predictive value for coronary artery disease remains unclear.

Researchers used multivariable-adjusted Cox regression models to examine the association between lipid parameters with incident coronary artery disease (CAD) in a prospective analysis of 207,368 UK Biobank participants. The participants had comprehensive lipoprotein profiling and no prior history of atherosclerotic disease, diabetes, or active lipid-lowering therapy. The researchers considered nuclear magnetic resonance-measured concentrations of apoB-P and individual lipoprotein classes, including very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), plus size subclasses, average particle diameter, and immunoassay-measured Lp(a).

Lipoprotein type or size of major apoB-P particles VLDL and LDL were generally not predictive for risk of coronary artery disease beyond total apoB-P count. Conversely, Lp(a) levels carried additional risk independent of apoB-P count. A 1 standard deviation increase in apoB-P was associated with a 33% higher CAD risk (hazards ratio [HR]: 1.33, 95% CI: 1.30-1.36). Although VLDL particles carried a higher per-particle risk (HR per 100 nmol/L: 1.22, 1.11-1.34) compared with LDL (HR per 100 nmol/L: 1.07, 1.05-1.08), this difference was counterbalanced after considering relative particle abundance (LDL 91% vs. VLDL 9% of total apoB-P). Thus, the respective hazard ratios per 1 standard deviation were 1.09 (1.05-1.14) and 1.24 (1.19-1.30). Particle diameter or size subclasses were not associated with CAD after apoB-P adjustment. Association of Lp(a) was robust even after apoB-P adjustment (HR: 1.18, 1.16-1.20) and added independent prognostic value for CAD (area under curve: 0.769 vs. 0.774, P < .001).