Triple positive CIRS: what the Shoemaker research shows, and what it doesn't

Ten people breathe the same musty air. One develops twenty overlapping symptoms across six body systems. The other nine are fine. Every standard lab on the sick one comes back normal, and a clinician calls it anxiety.

That sliver, the worst-affected patients often told there is nothing left to try, is exactly who a recent line of Shoemaker-lineage research is trying to describe. One forum poster put the experience plainly: "For 9 months I've been trying to get better without success. My blood tests are normal, my brain X-rays and MRI are normal. In my moldy house, there are 10 of us, and I'm the only one who's really sick. I don't understand" (r/ToxicMoldExposure).

This article walks through what the "triple positive" research actually claims, where it is genuinely interesting, and where it is early, unreplicated, and easy to over-read. It is a report on a small body of publications, not a settled finding, and not a description of how MoldCo cares for patients.

What the publications actually claim

"Triple positive" is a label used in Shoemaker-lineage publications for a transcriptomic subset of Chronic Inflammatory Response Syndrome (CIRS) patients, defined by a particular pattern of gene expression in blood. In a 2024 paper, that pattern was reported to substantially match the transcriptomic signature seen in symptomatic Parkinson's disease (Shoemaker et al., MRA 2024).

Two things are worth stating up front. First, "triple positive" describes a subset of CIRS, not a standalone diagnosis, and the popular shorthand of a single fixed "13-gene panel" oversimplifies it (the definition turns on which of several genes are up-regulated, not all of them at once). Second, this work comes from essentially one research group, published largely in the same journal, and has not yet been independently reproduced. Treat what follows as "here is what these papers say," not "here is established medicine."

What "triple positive" means

Transcriptomics reads which genes are currently being over- or under-expressed in your blood cells, rather than which genes you inherited. Where HLA genotyping asks "what DNA did you get at birth," transcriptomics asks "which genes are dialed up or down right now."

As defined in the 2024 paper, the triple positive pattern requires up-regulation across three areas at once (Shoemaker et al., MRA 2024):

• A tubulin gene: TUBA4A or TUBB1 (not necessarily both)
• Clusterin (CLU)
• At least 3 of 10 coagulation genes: F13A1, F5, GP6, GP9, ITGA2B, ITGB3, PF4, SELP, THBS1, TREM1

Each piece maps to a different strand of biology. Clusterin (CLU) is a chaperone protein involved in protein folding, cell death, and neuroprotection, and it has been implicated in several neurodegenerative diseases. The coagulation genes describe a more clot-prone vascular state. Tubulins are core building-block proteins found in almost all of the body's cells, not just neurons. The paper's interpretation is that, in this subset, those strands appear elevated together on top of an already inflammatory CIRS state.

In the same 2024 work the pattern was reported in roughly a third of a 102-patient clinic cohort (35.3%). That figure is higher than what many clinicians report seeing in practice, and it comes from a single retrospective study, so it is best read as a study result rather than an expected frequency.

The Parkinson's connection

The headline claim is that this gene-expression pattern is, in large part, the same fingerprint identified in symptomatic Parkinson's disease (PD). In the authors' words, it is "a unique transcriptomic fingerprint, including tubulin genes, densely found in symptomatic PD patients and much younger patients with fewer symptoms." They go further: "The discovery of this fingerprint in younger, asymptomatic patients introduces the possibility of a preclinical phase of PD where intervention could be most effective" (Shoemaker et al., MRA 2024).

That is the interesting part: the same pattern that shows up in older PD patients appears, per these papers, in some much younger CIRS patients before overt neurodegeneration, what the authors describe as a prodrome. It is a hypothesis-generating observation, not proof that CIRS causes Parkinson's. PD transcriptomics is an active independent research field in its own right (Nature Scientific Reports, 2024), but that broader field has not validated the triple positive construct specifically.

A few cautions the draft science itself supports. No brain-imaging finding has been correlated with this triple positive population; references to subcortical changes like caudate atrophy in the surrounding literature come from imaging work (e.g., NeuroQuant), not from these gene-expression results. We also deliberately avoid attributing the pattern to any specific exposure (such as endotoxins or particular bacteria); the gene-expression data does not establish that kind of specific causation, and treating it that way would overstate what is known.

Why to read this cautiously

External corroboration is thinner than it first appears. A 2025 review in a Shoemaker-affiliated context describes CIRS as a treatable condition and discusses transcriptomic "phases," but it is a descriptive review by an author connected to this lineage, not independent validation, and it does not tie a "neuroimmune risk profile" to caudate atrophy or peptide response the way a casual reading might suggest (Int. J. Mol. Sci. 2025). A 2024 review in Annals of Medicine & Surgery concluded the Shoemaker Protocol was the CIRS treatment with the most documented clinical efficacy in the literature it surveyed, but that review compared CIRS treatment with chronic-fatigue-syndrome treatment, it does not address Parkinson's, neurodegeneration, or triple positives, and its authors are trained in this protocol and provide expert-witness testimony in CIRS cases (Dooley et al., Ann Med Surg 2024).

On treatment specifically, be careful about what each paper supports. The 2024 paper states that, in a small study, treatment with a published CIRS protocol corrected many symptoms in triple positives while restoring more normal gene expression. The 2025 follow-up does not report treatment outcomes; it revisits the gene-expression findings and suggests protocol treatment in early PD or CIRS-PD may help arrest or even reverse progression (Shoemaker et al., MRA 2025). So the encouraging treatment language traces back to one small earlier study, not to two independent confirmations. None of it has been reproduced by another group.

The honest summary: this is an early, single-lineage, largely unreplicated hypothesis with a genuinely interesting Parkinson's overlap and a small, promising treatment signal. That is a reason to keep watching the research, not a reason to make decisions on it today.

What this means if you're a symptomatic patient now

Here is the practical part, and it is simpler than the science. You do not need gene-expression testing to get help, and reading your transcriptome is not how care should start.

MoldCo's model begins with a provider conversation about your exposure history and symptom pattern. MoldCo treats mold toxicity and does not diagnose CIRS. If labs are useful, the standard inflammatory-marker work (MMP-9, TGF-beta1, MSH) is available on a Starter Panel ($56 via LabCorp), and home dust testing (HERTSMI-2) is available through MoldCo's $199 home test. HLA genetic testing is available as an option, but it is interesting-to-know rather than required: you don't need a susceptibility haplotype to develop mold illness, and your HLA result doesn't change treatment.

Advanced transcriptomic testing (the kind used in the research above) is research-grade, is ordered only by a mold-literate physician outside of MoldCo, and is not a MoldCo product. It is not accessible to, or needed by, most patients. If treatment stalls, the first question is usually exposure: confirming you're actually out of the moldy environment, since leaving a building doesn't instantly stop the inflammatory cycle. From there, the work is the data-driven protocol, not chasing one more test.

If the last several years have been a tour of symptoms with no anchor, the most useful next step is a conversation that can sequence the work. Our overviews of the Shoemaker Protocol and the broader recovery roadmap lay out the phases, and mold illness testing walks through the tiers that actually apply to most patients.

"Exposed to high levels of toxic mold for months in a rental home. Brain fog, fatigue, sick more often, working memory clobbered. Treatment with MoldCo has been a huge blessing, finally recovering. If not for them mold wouldn't even be on my radar as a potential cause. Most doctors aren't trained to diagnose it."

— MoldCo patient

Start your care conversation runs as a telehealth visit, no thousands upfront, labs optional to begin.

Methodology and how this evidence is sourced

This piece reports on a small set of Shoemaker-lineage publications: Medical Research Archives (Shoemaker et al., 2024 and 2025), an Int. J. Mol. Sci. 2025 review, and an Annals of Medicine & Surgery 2024 review, with one independent PD-transcriptomics paper for field context. We have tried to report what each paper says and to flag where claims have been over-extended in popular summaries. The 2025 paper in particular is difficult to access in searchable form, so its details are reported conservatively.

Patient voices are illustrative, not diagnostic. Testimonials are verbatim public reviews, attributed as "MoldCo patient" to protect privacy.

Limitations and open questions

• Single lineage, not yet reproduced. The triple positive finding comes essentially from one group, published largely in one journal; the peer-review details are not transparent, and no independent team has reproduced it.
• "Triple positive" is a subset label, not a diagnosis. It describes up-regulation of some of a defined gene set, and the tidy "13-gene panel" shorthand can mislead.
• No imaging or causal proof. No brain-imaging finding has been correlated with this specific population, and the gene-expression data does not establish a specific exposure cause.
• Treatment evidence is thin. The encouraging treatment signal is from one small earlier study; the 2025 follow-up did not measure treatment outcomes.
• Access and necessity. Research-grade transcriptomic testing is not a MoldCo offering, requires a mold-literate physician, and is neither accessible to nor needed by most patients.

FAQ

Do I need transcriptomic (gene-expression) testing to start care?

No. Care begins with a provider conversation about exposure history and symptom pattern. Gene-expression testing is a research tool, not a prerequisite, and not a MoldCo offering. Most patients never need it.

Is the "triple positive Parkinson's" finding established science?

Not yet. It comes from a small number of papers from one research lineage and has not been independently reproduced. The Parkinson's-signature overlap is a genuinely interesting hypothesis, but it should be read as early research, not a confirmed link between CIRS and Parkinson's disease.

I left the moldy building a while ago. Can I still feel sick?

Yes. Leaving exposure doesn't automatically switch off the inflammatory cycle, which is part of why avoidance alone is often not enough at the severe end and why a structured, clinician-guided approach matters. If treatment stalls, confirming you are truly out of ongoing exposure is usually the first thing to revisit.

Is gene-expression testing the same as HLA genetic testing?

No. HLA testing reads the inherited DNA you were born with (a susceptibility marker that doesn't change treatment). Gene-expression (transcriptomic) testing reads which genes are currently up- or down-regulated. They answer different questions, and neither is required to begin care.

Where is MoldCo available?

Availability changes regularly, so check the current supported states page. Telehealth care reaches many states; at-home blood draws are restricted in a few states by longer-standing lab regulations, but the HERTSMI-2 home dust test is available nationwide.

Any health-related claims made on this site have not been evaluated by the Food and Drug Administration (FDA). The information provided on this site is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. MoldCo assumes no responsibility or liability for any errors or omissions in the content of the references, nor for any actions taken in reliance thereon.