Pharmacodiagnostic Origin Inference: Epistemology and Methodology

1 Maziarz 2024 — Causal Pluralism in Medicine

Full Citation:: Maziarz M. Causal Pluralism in Medicine and its Implications for Clinical Practice. Journal for General Philosophy of Science. 2024;55(3):377–398. (Maziarz 2024)
DOI:: 10.1007/s10838-023-09658-1
PMID:: 39554999
Study Design:: Philosophy of medicine analysis
Key Findings::
- Three types of causal claims in medicine: manipulationist (RCT), probabilistic (observational epidemiology), mechanistic (laboratory research)
- RCTs support intervention therapeutic decisions; observational studies support prediction; mechanistic studies support interference
- Each type of causal claim delivers evidence for different types of therapeutic decisions
Conclusion:: Causal pluralism constrains what null trials can conclude. A null RCT rules out current manipulable causation but does NOT rule out historical causal roles or mechanistic contributions at sub-threshold levels.
Pharmacodiagnostic Relevance:: When rituximab is null in ME/CFS, this rules out B-cell autoantibody production as a currently manipulable cause of symptoms but does NOT rule out a historical autoimmune trigger that has burned out or autoantibodies confined to undetectable subgroups. The distinction between manipulable cause and historical trigger is the key contribution to pharmacodiagnostic origin inference.
Certainty:: 0.55 (philosophy; not empirical)

2 De Pretis et al. 2019 — E-Synthesis Bayesian Framework

Full Citation:: De Pretis F, Landes J, Osimani B. E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance. Frontiers in Pharmacology. 2019;10:1317. (De Pretis, Landes, and Osimani 2019)
DOI:: 10.3389/fphar.2019.01317
PMID:: 31920632
Study Design:: Bayesian methodology development with case study application
Key Findings::
- Bayesian framework aggregating multiple evidence types (anecdotal reports, case series, RCTs, observational studies) to assess causal probability
- Introduces evidential modulators bearing on reliability of incoming study results
- Exploits coherence of independent evidence converging toward hypothesis
- Integrates heterogeneous data types and methods into single inferential framework
Conclusion:: E-Synthesis provides mathematically rigorous infrastructure for formal pharmacodiagnostic inference. Multiple drug-response signals can be integrated into a single posterior probability for each origin hypothesis.
Pharmacodiagnostic Relevance:: Methodological backbone for a formal pharmacodiagnostic matrix. If a patient has null response to drug A (targeting mechanism X) but positive response to drug B (targeting mechanism Y), each response updates posterior probability of competing origin hypotheses via Bayesian calculus. Currently no disease uses such a system.
Certainty:: 0.60 (rigorous methodology; ERC-funded)

3 Borck and Lohse 2026 — Uncertainty in Precision Medicine

Full Citation:: Borck C, Lohse S. Sorting out and navigating uncertainty in precision medicine. History and Philosophy of the Life Sciences. 2026;48(2):21. (Borck and Lohse 2026)
DOI:: 10.1007/s40656-026-00726-5
PMID:: 41876830
Study Design:: Philosophy of medicine analysis; Cluster of Excellence Precision Medicine in Chronic Inflammation
Key Findings::
- Three uncertainty types: socio-technical, epistemological, ontological
- Ontological uncertainty from biological complexity itself is non-transient; cannot be overcome by more data
- Precision medicine paradox: more personalized data can increase uncertainty because complexity becomes more visible
Conclusion:: Some origin-level questions may be inherently unanswerable via treatment response due to ontological uncertainty.
Pharmacodiagnostic Relevance:: If ME/CFS involves multiple parallel pathways, drug responses will be confounded by subset-specific mechanisms, compensatory pathway activation, and non-stationary disease states. The pharmacodiagnostic matrix must acknowledge that some origin inferences may be underdetermined by even complete drug-response data.
Certainty:: 0.50 (philosophy; informed by clinical experience)

4 Fischer and Jukola 2026 — Experimental Evidence and Exclusion Reasoning

Full Citation:: Fischer E, Jukola S. Studying asphyxiation in the lab: the role of experimental evidence in cause-of-death inquiry. History and Philosophy of the Life Sciences. 2026;48(1):9. (Fischer and Jukola 2026)
DOI:: 10.1007/s40656-025-00712-3
PMID:: 41553635
Study Design:: Philosophy of science analysis (forensic medicine)
Key Findings::
- Experimental evidence identifies or excludes potential causes – not definitive causes
- Key function: rebut claims to impossibility; concept of false advertising (mismatch between methodology and goals)
- Laboratory evidence constrains but does not determine case-level causation
Conclusion:: The logic of exclusion is valid but limited. A null drug trial can eliminate a mechanism as a current disease driver but does not establish what IS driving the disease.
Pharmacodiagnostic Relevance:: A null result rules out the specific mechanism the drug targets only if: (1) drug achieves target engagement, (2) the mechanism is necessary for symptom maintenance, and (3) the trial has adequate power. The false advertising concept warns against claiming a null trial eliminates an origin hypothesis when it only tests one downstream mechanism.
Certainty:: 0.45 (philosophy; forensic application)

5 Meyer 2026 — Bayesian Methods and Null-Result Interpretation

Full Citation:: Meyer N. The Contribution of Bayesian Methods in Solving the Paradoxes of Classical Statistical Tests in Biomedical Research. Journal of Clinical Medicine. 2026;15(6):2262. (Meyer 2026)
DOI:: 10.3390/jcm15062262
PMID:: 41899186
Study Design:: Educational/commentary; non-empirical
Key Findings::
- Frequentist p-values conflate Fisher and Neyman-Pearson frameworks creating paradoxes in clinical reasoning
- p > 0.05 means data compatible with null – NOT null hypothesis established
- Bayesian posterior probability is the correct metric: probability that treatment has no effect is X percent
Conclusion:: A null RCT should update posterior probability toward (but never to) certainty of null. The magnitude depends on trial power, prior probability, and coherence with other evidence.
Pharmacodiagnostic Relevance:: The Fluge 2019 trial at n=151 has reasonable power making the null fairly informative – but the posterior cannot reach zero. The correct interpretation is rituximab null reduces posterior probability of B-cell-dependent autoimmune mechanism from prior to posterior instead of rituximab null proves autoimmune mechanism absent.
Certainty:: 0.40 (educational; non-empirical)

6 Oea et al. 2024 — ME/CFS Clinical Trials Overview

Full Citation:: Oea N, et al. Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives. Journal of Clinical Medicine. 2024;13(2):325. (Oea et al. 2024)
DOI:: 10.3390/jcm13020325
PMID:: 38256459
Study Design:: Narrative review
Key Findings::
- Comprehensive overview of ME/CFS clinical trials
- Documents rituximab trajectory: Phase I case series to Phase II positive to Phase III negative
- Situates null within broader immunomodulatory landscape (daratumumab, cyclophosphamide, immunoadsorption)
Conclusion:: The rituximab null does NOT falsify autoimmune hypothesis broadly – it specifically eliminates B-cell depletion as effective. Plasma cell targeting (daratumumab) may succeed where B-cell depletion failed.
Pharmacodiagnostic Relevance:: If daratumumab (anti-CD38, targeting long-lived plasma cells) shows benefit where rituximab (anti-CD20, targeting B-cells) did not, this refines pharmacodiagnostic inference: autoantibodies ARE relevant but from CD20-negative plasma cells, not B-cells.
Certainty:: 0.50 (narrative review; no new data)

7 Sepúlveda et al. 2024 — EBV IgG Responses and Antigenic Mimicry

Full Citation:: Sepúlveda M, et al. IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry. Medicina. 2024;60(1):161. (Sepúlveda et al. 2024)
DOI:: 10.3390/medicina60010161
PMID:: 38256421
Study Design:: Case-control immunoprofiling
Key Findings::
- EBV IgG responses in ME/CFS show distinct patterns vs healthy controls supporting antigenic mimicry
- Elevated EBV antibodies do NOT necessarily indicate ongoing viral replication; may reflect persistent immune memory or mimicry-driven autoreactivity
Conclusion:: EBV antibody elevation in ME/CFS is compatible with both viral persistence AND post-infectious autoimmunity. Distinguishing between these requires treatment response data.
Pharmacodiagnostic Relevance:: If EBV antibodies elevated but valacyclovir (anti-EBV) is null, this supports antigenic mimicry over active viral replication as origin. If valganciclovir (broader spectrum) responds in subset, this suggests HHV-6 or CMV specifically rather than EBV.
Certainty:: 0.55 (case-control; single study)

8 Rekeland et al. 2024 — Six-Year Follow-up of Rituximab/Cyclophosphamide Trials

Full Citation:: Rekeland IG, Sørland K, Neteland LL, Fosså A, Alme K, Risa K, Dahl O, Tronstad KJ, Mella O, Fluge Ø. Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PLoS One. 2024;19(7):e0307484. (Rekeland et al. 2024)
DOI:: 10.1371/journal.pone.0307484
PMID:: 39042627
PMCID:: PMC11265720
Study Design:: Long-term follow-up of completed RCTs
Sample Size:: n=151 (Fluge 2019 + cyclophosphamide trial participants)
Key Findings::
- At six-year follow-up, no divergence between rituximab vs placebo groups
- No long-term benefit from having received rituximab during the trial period
- Eliminates hypothesis that clinical benefits from B-cell depletion could emerge years after treatment
Conclusion:: B-cell depletion produces no delayed or long-term benefit in ME/CFS. The null at 24 months (Fluge 2019) is not due to insufficient follow-up duration.
Pharmacodiagnostic Relevance:: Strengthens origin-level inference from the rituximab null. Combined with daratumumab pilot (Fluge 2025, targeting CD38+ plasma cells): if daratumumab succeeds where rituximab failed, relevant autoantibody-producing cells are CD20-negative long-lived plasma cells.
Certainty:: 0.70 (long follow-up; full original cohort; PLoS One)

9 Weipert et al. 2025 — RAPID Adaptive Platform Trial Protocol

Full Citation:: Weipert L, Telgmann RG, Anton G, et al. Randomized adaptive assessment of post COVID syndrome treatments (RAPID): a study protocol for a multicenter, randomized, controlled adaptive platform trial of treatment options for Post Covid Syndrome (PCS) including the first intervention specific appendix RAPID_REVIVE. Trials. 2025;26(1):297. (Weipert et al. 2025)
DOI:: 10.1186/s13063-025-09008-0
PMID:: 40830806
Study Design:: Clinical trial protocol (adaptive platform design)
Key Findings::
- Master protocol for adaptive platform trial testing multiple PCS treatments; first ISA tests antiviral vidofludimus calcium vs placebo
- Primary outcome: SF-36 Physical Function change from baseline to day 56
- Response-adaptive randomization after initialization phase
Conclusion:: Protocol only – no efficacy results. Platform design enables testing multiple treatments simultaneously, producing multi-drug response data to constrain origin inference. If antiviral is null in PCS patients meeting ME/CFS criteria, this constrains viral persistence hypothesis.
Pharmacodiagnostic Relevance:: Platform trial architecture is the design needed for a proper pharmacodiagnostic matrix: multiple drugs tested in parallel against common control producing cross-drug response comparisons and origin inferences. Demonstrates this is feasible in post-infectious fatigue syndromes.
Certainty:: 0.40 (protocol only; no results)

10 Wormgoor et al. 2026 — Wheat and Chaff in ME/CFS

Full Citation:: Wormgoor M, et al. Wheat and chaff in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) in clinics and laboratory. Journal of Translational Medicine. 2026;24. (Wormgoor et al. 2026)
DOI:: 10.1186/s12967-025-07397-z
PMID:: 41491817
Study Design:: Critical review / opinion
Key Findings::
- Systematic separation of evidence-based from speculative claims in ME/CFS diagnostics and therapy
- Wheat and chaff framing applied to both clinical and laboratory claims
Conclusion:: Significant portion of ME/CFS clinical claims lack adequate evidence. Pharmacodiagnostic inference must distinguish treatment responses that genuinely narrow mechanism from those confounded by placebo or natural history.
Pharmacodiagnostic Relevance:: The pharmacodiagnostic matrix must include quality filters for which drug responses count as evidence. Some responses are informative (true wheat) while others are noise (chaff).
Certainty:: 0.35 (opinion/review; no empirical data)

11 Finlay et al. 2020 — 100 Years of Ligand–Receptor Binding and Response

Full Citation:: Finlay DB, Duffull SB, Glass M. 100 years of modelling ligand–receptor binding and response: a focus on GPCRs. British Journal of Pharmacology. 2020;177(7):1501-1520. (Finlay, Duffull, and Glass 2020)
DOI:: 10.1111/bph.14907
PMID:: 31739586
Study Design:: Comprehensive methodological review
Key Findings::
- Reviews 100 years of receptor occupancy theory development
- Formalizes relationship between receptor occupancy and response (non-linear, spare receptors)
- Covers competitive antagonism: pA2, pKB derivation, Schild analysis
- Distinguishes competitive vs non-competitive vs allosteric antagonism
- Addresses null methods for defining “receptor pharmacology” — when no response occurs despite receptor presence
Null-Subtyping Relevance:: Provides the quantitative framework for distinguishing ABSENT (no binding site) from BLOCKED (competitor occupies site) from functional antagonism. A drug’s null response at a given concentration does not imply receptor absence — it may reflect competitive blockade, receptor reserve, or allosteric modulation.
Certainty:: 0.90 (Br J Pharmacol; comprehensive review of century-old established theory)

12 Skiba & Kruse 2021 — Autoantibodies as Endogenous Modulators of GPCR Signaling

Full Citation:: Skiba MA, Kruse AC. Autoantibodies as endogenous modulators of GPCR signaling. Trends in Pharmacological Sciences. 2021;42(3):135-150. (Skiba and Kruse 2021)
DOI:: 10.1016/j.tips.2020.11.013
PMID:: 33461756
Study Design:: Review with structural biology integration
Key Findings::
- Autoantibodies targeting GPCRs can act as orthosteric antagonists, allosteric modulators, biased agonists, or inverse agonists
- AAb binding to GPCR extracellular loops (ECL1, ECL2, ECL3) produces distinct functional outcomes: ECL2 binding commonly agonist-like; ECL1 can produce antagonism
- AAb promote receptor internalization and desensitization via β-arrestin recruitment
- Allosteric small molecules can still bind and modulate GPCR function even when orthosteric site is AAb-occupied
- Structural approaches (cryo-EM, X-ray) now enable epitope mapping for AAb-GPCR complexes
Null-Subtyping Relevance:: Establishes that GPCR autoantibodies produce the BLOCKED null subtype — receptor structurally present but orthosteric site occupied. Allosteric ligands can bypass this block, providing a diagnostic probe distinguishing BLOCKED from ABSENT. AAb-mediated internalization creates hybrid BLOCKED/ABSENT state: receptor structurally present but functionally depleted from membrane.
Certainty:: 0.85 (Trends Pharmacol Sci; well-established pharmacology)

13 Sunami et al. 2025 — GPCR Autoimmunity in POTS

Full Citation:: Sunami Y, Sugaya K, Takahashi K. G protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome. Immunological Medicine. 2025;48(1):1-11. (Sunami, Sugaya, and Takahashi 2025)
DOI:: 10.1080/25785826.2025.2457613
PMID:: 39885707
Study Design:: Review
Key Findings::
- POTS adrenergic receptor autoantibodies exert allosteric effects on phenylephrine response
- M2 muscarinic receptor autoantibodies produce negative allosteric modulation
- POTS AAb activated α1 and β2 adrenergic receptors via allosteric mechanism
- Distinguishes stimulatory from inhibitory AAb functional profiles
Null-Subtyping Relevance:: Direct clinical-context evidence for the BLOCKED null subtype. A POTS patient with negative allosteric M2 AAb would show null response to an orthosteric M2 agonist — but an allosteric M2 positive modulator could restore function. Validates the allosteric bypass probe concept in a dysautonomia population overlapping with ME/CFS.
Limitations:: Relies primarily on CellTrend ELISA methodology; functional assay replication pending.
Certainty:: 0.50 (Immunol Med; recent review; methodology concerns)

14 Dodge-Kafka et al. 2026 — β-Adrenergic Receptor Autoantibody Functional Effects

Full Citation:: Dodge-Kafka KL, Turcotte MG, Possidento SM, et al. β-Adrenergic Receptors: Not Always Outside-In. Physiology. 2026;41(4). (Dodge-Kafka et al. 2026)
DOI:: 10.1152/physiol.00026.2025
Study Design:: Review with mechanistic focus
Key Findings::
- β1AR autoantibodies reduce plasma membrane receptor expression (internalization)
- Sustained AAb activation produces chronic homologous desensitization
- β-arrestin-biased signaling: AAb activates β-arrestin pathway while Gαs pathway is desensitized
- This creates a pathway-specific partial null: drugs signaling through Gαs show null response while β-arrestin pathway remains active
Null-Subtyping Relevance:: Documents a key nuance in the BLOCKED null subtype — the receptor may be functionally null for specific signaling pathways while structurally present. A drug relying on Gαs coupling (e.g., standard β-agonist for cAMP elevation) would appear null, but a β-arrestin-biased ligand could still produce response. This refines the allosteric bypass probe to include biased-ligand probes.
Certainty:: 0.55 (Physiology; 2026; recent review bridging basic to clinical pharmacology)

15 Kavyani et al. 2024 — Kynurenine Pathway Dysregulation in ME/CFS

Full Citation:: Kavyani B, Ahn SB, Missailidis D, Annesley SJ, Fisher PR, Guillemin GJ, et al. Dysregulation of the kynurenine pathway, cytokine expression pattern, and proteomics profile link to symptomology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Molecular Neurobiology. 2024;61(7):4728-4748. (Kavyani et al. 2024)
DOI:: 10.1007/s12035-023-03756-w
PMID:: 38097810
Study Design:: Case-control multi-omics
Sample Size:: ME/CFS patients (exact n not in abstract)
Key Findings::
- ME/CFS patients show altered tryptophan metabolism via the kynurenine pathway
- Reduced KYNA/QUIN ratio — neuroprotective KYNA depleted relative to neurotoxic QUIN
- Cytokines (IL-1β, TNF) correlated with kynurenine pathway enzyme expression
- Kynurenine pathway metabolites linked to proteomics-based symptom clusters
- IDO-1/TDO activation confirmed in immune–metabolic dysregulation
Null-Subtyping Relevance:: This study shows KYNA depletion (not elevation) in ME/CFS. For the OVERWHELMED null subtype (elevated KYNA outcompeting drugs at NMDA receptors), this implies the subtype applies only to the KYNA-elevated subpopulation. The direction of KYNA dysregulation may differ by disease phase or inflammatory state. In the KYNA-depleted state, NMDAR drugs would show enhanced (not null) responses. Pharmacodiagnostic probing requires measuring KYNA levels before drug testing.
Limitations:: Single study; KYNA level direction inconsistent across literature; need CSF measurements and pre/post-exercise comparisons.
Certainty:: 0.60 (Mol Neurobiol; direct ME/CFS study; multi-omics; single cohort)

16 Hazrati et al. 2024 — Kynurenine Pathway Across Chronic Pain Conditions

Full Citation:: Hazrati E, Eftekhar SP, Mosaed R, et al. Understanding the kynurenine pathway: a narrative review on its impact across chronic pain conditions. Molecular Pain. 2024;20:17448069241297714. (Hazrati et al. 2024)
DOI:: 10.1177/17448069241297714
PMID:: 39618145
Study Design:: Narrative review
Key Findings::
- Covers kynurenine pathway in chronic pain, fibromyalgia, CFS/ME, and MDD
- KYNA acts as endogenous NMDA receptor antagonist at the glycine co-agonist site (not the glutamate site)
- 7-Cl-KYNA is a synthetic analog with higher NMDA antagonist potency — potential positive control for KYNA probe design
- KYNA also antagonizes α7 nicotinic acetylcholine receptors
- Kynurenine pathway activation driven by IDO/TDO in response to inflammatory cytokines
Null-Subtyping Relevance:: The glycine-site binding of KYNA at NMDA receptors determines probe design for the OVERWHELMED null subtype. Because KYNA competes at the glycine co-agonist site, the concentration-competition probe must use a glycine-site agonist or glycine itself — not a glutamate-site NMDA agonist. This distinguishes KYNA-mediated OVERWHELMED from anti-NMDAR autoantibody-mediated BLOCKED (where the receptor itself is targeted).
Certainty:: 0.45 (Mol Pain; narrative review; heterogeneous conditions; no ME/CFS-specific data)

References

Borck, Cornelius, and Simon Lohse. 2026. “Sorting Out and Navigating Uncertainty in Precision Medicine.” History and Philosophy of the Life Sciences 48 (2): 21. https://doi.org/10.1007/s40656-026-00726-5.

De Pretis, Francesco, Jürgen Landes, and Barbara Osimani. 2019. “E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance.” Frontiers in Pharmacology 10: 1317. https://doi.org/10.3389/fphar.2019.01317.

Dodge-Kafka, Kimberly L., Matthew G. Turcotte, Stephanie M. Possidento, et al. 2026. “Β-Adrenergic Receptors: Not Always Outside-in.” Physiology 41 (4). https://doi.org/10.1152/physiol.00026.2025.

Finlay, David B., Stephen B. Duffull, and Michelle Glass. 2020. “100 Years of Modelling Ligand–Receptor Binding and Response: A Focus on GPCRs.” British Journal of Pharmacology 177 (7): 1501–20. https://doi.org/10.1111/bph.14907.

Fischer, Enno, and Saana Jukola. 2026. “Studying Asphyxiation in the Lab: The Role of Experimental Evidence in Cause-of-Death Inquiry.” History and Philosophy of the Life Sciences 48 (1): 9. https://doi.org/10.1007/s40656-025-00712-3.

Hazrati, Ebrahim, Seyed Parsa Eftekhar, Reza Mosaed, et al. 2024. “Understanding the Kynurenine Pathway: A Narrative Review on Its Impact Across Chronic Pain Conditions.” Molecular Pain 20: 17448069241297714. https://doi.org/10.1177/17448069241297714.

Kavyani, Behrouz, Seong Beom Ahn, Daniel Missailidis, Sarah J. Annesley, Paul R. Fisher, Gilles J. Guillemin, et al. 2024. “Dysregulation of the Kynurenine Pathway, Cytokine Expression Pattern, and Proteomics Profile Link to Symptomology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).” Molecular Neurobiology 61 (7): 4728–48. https://doi.org/10.1007/s12035-023-03756-w.

Maziarz, Mariusz. 2024. “Causal Pluralism in Medicine and Its Implications for Clinical Practice.” Journal for General Philosophy of Science 55 (3): 377–98. https://doi.org/10.1007/s10838-023-09658-1.

Meyer, Nicolas. 2026. “The Contribution of Bayesian Methods in Solving the Paradoxes of Classical Statistical Tests in Biomedical Research.” Journal of Clinical Medicine 15 (6): 2262. https://doi.org/10.3390/jcm15062262.

Oea, N. et al. 2024. “Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.” Journal of Clinical Medicine 13 (2): 325. https://doi.org/10.3390/jcm13020325.

Rekeland, Ingrid G., Kari Sørland, Linn L. Neteland, Alexander Fosså, Kari Alme, Kristin Risa, Olav Dahl, Karl J. Tronstad, Olav Mella, and Øystein Fluge. 2024. “Six-Year Follow-up of Participants in Two Clinical Trials of Rituximab or Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” PLoS One 19 (7): e0307484. https://doi.org/10.1371/journal.pone.0307484.

Sepúlveda, M. et al. 2024. “IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.” Medicina 60 (1): 161. https://doi.org/10.3390/medicina60010161.

Skiba, Meredith A., and Andrew C. Kruse. 2021. “Autoantibodies as Endogenous Modulators of GPCR Signaling.” Trends in Pharmacological Sciences 42 (3): 135–50. https://doi.org/10.1016/j.tips.2020.11.013.

Sunami, Yutaro, Kazushi Sugaya, and Kazushi Takahashi. 2025. “G Protein-Coupled Receptors Related to Autoimmunity in Postural Orthostatic Tachycardia Syndrome.” Immunological Medicine 48 (1): 1–11. https://doi.org/10.1080/25785826.2025.2457613.

Weipert, Lisa, Ralph G. Telgmann, Gabriele Anton, Thomas Asendorf, Irina Chaplinskaja-Sobol, Sandra Ciesek, Oliver A. Cornely, et al. 2025. “Randomized Adaptive Assessment of Post COVID Syndrome Treatments (RAPID): A Study Protocol for a Multicenter, Randomized, Controlled Adaptive Platform Trial of Treatment Options for Post Covid Syndrome.” Trials 26 (1): 297. https://doi.org/10.1186/s13063-025-09008-0.

Wormgoor, M. et al. 2026. “Wheat and Chaff in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Clinics and Laboratory.” Journal of Translational Medicine 24. https://doi.org/10.1186/s12967-025-07397-z.