Small Clinic Study Finds Elevated Inflammatory Markers in Most ASD Children Tested, But Design Limits What This Proves

A retrospective case series of 42 children with autism spectrum disorder reports high rates of cytokine and prostaglandin abnormalities across multiple inflammatory biomarkers, but the absence of a matched control group, inconsistent testing across patients, and potential commercial conflicts substantially constrain the clinical inferences that can be drawn from these findings.

Why This Matters

Immune dysregulation in autism spectrum disorder has become one of the most actively discussed topics in both research and parent-facing clinical communities. The hypothesis that systemic or gut-localized inflammation contributes to ASD pathophysiology has drawn significant scientific interest, and a growing number of clinics now offer broad inflammatory biomarker panels to families seeking answers. When small clinical reports advocate for routine inflammatory profiling without the methodological rigor to support that recommendation, the risk of premature adoption into practice, and the financial and emotional costs to families, becomes a serious concern that warrants careful evidence appraisal.

Clinical Summary

Autism spectrum disorder affects roughly one in 36 children in the United States, and the search for reliable biomarkers that might guide individualized treatment remains one of the field’s central challenges. This 2018 brief communication by Borruel and colleagues, published in the Journal of Personalized Medicine, reports retrospective laboratory data from 42 ASD-diagnosed children (ages 3 to 17) evaluated at a single Belgian clinic. The rationale centers on a well-established line of research suggesting that subsets of individuals with ASD exhibit altered immune signaling, including elevated pro-inflammatory cytokines, disrupted mucosal immunity, and neuroinflammatory cascades that may influence neurodevelopment and behavior. The authors assessed a panel of biomarkers spanning serum cytokines, prostaglandin E2, elastase mRNA, soluble CD14, and fecal secretory IgA, with analyses performed at R.E.D. Laboratories.

The reported frequencies of abnormality are notable: 86.5% of tested patients showed elevated interleukin-8, 71% showed elevated prostaglandin E2, 57% elevated monocyte chemoattractant protein-1, 47% elevated interleukin-1 beta, 41% elevated elastase, and 68% showed abnormal fecal secretory IgA. However, these percentages derive from variable subsets of the 42 patients, as not all individuals underwent the same tests. Critically, “abnormal” was defined by comparison to reference ranges from a separate, unmatched healthy cohort rather than a concurrent matched control group. The authors are affiliated with the commercial laboratory that performed the testing, and patients were recruited from a clinic already oriented toward biomedical approaches, introducing substantial selection and commercial bias. The paper does not report whether biomarker levels correlated with ASD severity or clinical outcomes, and the authors themselves frame the work as awareness-raising rather than hypothesis-testing, acknowledging the need for larger controlled studies.

Dr. Caplan’s Take

Families of children with ASD frequently ask whether inflammatory testing can help explain their child’s symptoms or guide treatment. I understand the appeal of this study’s findings: high percentages, multiple markers, and a narrative that suggests actionable biology. What the study gets right is that immune dysregulation in ASD is a legitimate and important area of investigation, supported by stronger controlled research elsewhere. But this particular report, a retrospective look at 42 patients from a single clinic without matched controls, cannot tell us whether these elevations are characteristic of ASD broadly, whether they correlate with symptoms, or whether acting on them improves outcomes. The gap between mechanistic plausibility and clinical utility remains wide.

In practice, I do not recommend broad inflammatory biomarker panels for ASD patients based on evidence at this level. When families bring results from such panels, I help them understand what the numbers can and cannot mean. I focus instead on evidence-based behavioral and developmental interventions, address gastrointestinal or immune symptoms when they are clinically apparent, and remain transparent that while the science of immune-ASD connections is evolving, we are not yet at a point where routine inflammatory profiling changes management in a way that has been shown to benefit children.

Clinical Perspective

This study sits very early in the research arc for inflammatory biomarker profiling in ASD. While well-designed case-control and cohort studies have demonstrated group-level differences in cytokine profiles between ASD and neurotypical populations, translating those population-level observations into clinically actionable individual-level testing requires prospective validation, standardized assay protocols, and evidence that acting on results changes outcomes. This case series confirms that a convenience sample enriched for biomedical evaluation referrals shows high rates of inflammatory marker abnormality, but it cannot distinguish whether these findings generalize beyond this selected population. The absence of matched controls and the variable testing across patients mean the reported prevalence figures should not be cited as representative of ASD as a whole.

Clinicians should be aware that commercial inflammatory panels marketed for ASD evaluation currently lack the validation needed to meet standard diagnostic thresholds. Prostaglandin E2, several of the cytokines measured here, and fecal secretory IgA can fluctuate with infection, diet, stress, and medication use, meaning isolated abnormalities in a clinical setting are difficult to interpret without longitudinal and contextual data. There are no known drug interaction concerns specific to the biomarker testing itself, but treatment decisions based on unvalidated panel results, such as empiric anti-inflammatory supplementation, carry their own risk-benefit considerations. The single most actionable recommendation is to evaluate gastrointestinal and immune symptoms in ASD patients on their own clinical merits, using established diagnostic criteria, rather than relying on broad screening panels that have not been shown to improve outcomes.

Study at a Glance

Study Type

Retrospective case series (brief communication)

Population

42 children with ASD (ages 3 to 17), single Belgian clinic; 79 healthy controls for PGE2 reference ranges only

Intervention

Inflammatory biomarker panel (cytokines, PGE2, elastase mRNA, sCD14, fecal sIgA)

Comparator

Separate unmatched healthy cohort reference ranges; no concurrent matched controls

Primary Outcomes

Proportion of tested ASD patients with biomarker values outside healthy reference ranges

Sample Size

42 ASD patients (variable subsets tested per biomarker); 79 healthy controls (reference only)

Journal

Journal of Personalized Medicine

Year

2018

DOI or PMID

Not specified in source data

Funding Source

Not formally disclosed; authors affiliated with R.E.D. Laboratories (performing lab)

What Kind of Evidence Is This

This is a retrospective case series presented as a brief communication, which occupies one of the lowest tiers in the evidence hierarchy. Case series can generate hypotheses and document clinical observations, but they cannot establish causation, determine prevalence in a broader population, or support clinical recommendations for diagnostic testing. The single most important inference constraint is the absence of a concurrent matched control group: without one, we cannot determine whether the observed biomarker frequencies differ meaningfully from what would be found in age-matched neurotypical children tested under identical conditions.

How This Fits With the Broader Literature

The finding that subsets of ASD patients show elevated pro-inflammatory cytokines is broadly consistent with larger, better-controlled studies. Mead and Ashwood (2015) conducted a systematic review documenting elevated IL-1 beta, IL-6, IL-8, and TNF-alpha in ASD across multiple case-control studies with matched neurotypical comparison groups. Ashwood and colleagues (2011) demonstrated in a well-designed prospective study that plasma cytokine profiles correlated with behavioral severity in ASD children, providing the kind of outcome linkage absent from the current report.

What this case series adds is limited. It confirms that patients already referred for biomedical evaluation at a specialized clinic show high rates of inflammatory marker abnormality, but this is expected given the referral context and does not extend the inferential reach of the controlled literature. Its primary contribution is as a clinical practice description rather than a scientific advance.

Common Misreadings

The most likely overinterpretation is reading the high percentages (86.5% elevated IL-8, 71% elevated PGE2) as evidence that most children with ASD have clinically meaningful inflammation that should be routinely tested and treated. This exceeds the evidence for several reasons. The patients were drawn from a clinic specializing in biomedical approaches, creating selection bias toward individuals with suspected inflammatory symptoms. The comparison was to a separate reference range rather than matched controls, inflating apparent abnormality rates. And not all patients received the same tests, meaning each percentage reflects a different, potentially non-representative subset. Without prospective replication in unselected ASD populations using matched concurrent controls, these figures should not be generalized.

Bottom Line

This retrospective case series documents that children with ASD referred to a biomedically oriented clinic frequently show inflammatory biomarker elevations. It does not establish that these elevations are characteristic of ASD broadly, that they are causally related to ASD symptoms, or that testing for them improves clinical outcomes. The findings are hypothesis-generating and consistent with stronger controlled research, but they do not support routine inflammatory profiling as part of ASD management at this time.

References

1. Borruel N, De Meirleir K, et al. Inflammatory biomarkers in autism spectrum disorder: a brief report. Journal of Personalized Medicine. 2018.
2. Mead J, Ashwood P. Evidence supporting an altered immune response in ASD. Immunology Letters. 2015;163(1):49-55.
3. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain, Behavior, and Immunity. 2011;25(1):40-45.