Cano-Cano 2026 — multimodal NfL + GFAP + RNFL + GMV cross-disease biomarker template

One-paragraph summary

Cano-Cano et al ran a cross-sectional comparative profiling study across newly-diagnosed T1DM (n=18), relapsing-remitting MS (n=26), and healthy controls (n=20), with an exploratory long-duration T1DM arm (n=12). They combined neuropsychological + clinical evaluation, cellular immune profiles, advanced neuroimaging (whole-brain and regional grey-matter volumetry, OCT-RNFL), and serum biomarkers (sNfL, GFAP). Both newly-diagnosed disease groups showed cognitive/mood disturbances and elevated sNfL relative to controls; MS specifically showed thalamic volume reduction and RNFL thinning. This is the multimodal biomarker-panel template the project's retinal-biomarker-diagnostic priority document calls for — adapted directly to FM, it would supply the methodology stack for a within-FM autoimmune-subtype stratification study with the same panel of measurements.

Claims as triples

• serum_NfL_level — elevated_in → multiple_sclerosis [evidence: between-group comparison MS vs HC; confidence: established (replicates known finding)]
• serum_NfL_level — elevated_in → type_1_diabetes_newly_diagnosed [evidence: between-group comparison T1DM vs HC; confidence: emerging — novel framing of T1DM as neurodegenerative]
• OCT_RNFL_thickness — reduced_in → multiple_sclerosis [evidence: optical coherence tomography measurement; confidence: established (replicates known finding)]
• thalamus_volume — reduced_in → multiple_sclerosis [evidence: regional grey-matter volumetry; confidence: established]
• cognitive_dysfunction — present_in → multiple_sclerosis_newly_diagnosed [evidence: neuropsychological assessment; confidence: established]
• cognitive_dysfunction — present_in → type_1_diabetes_newly_diagnosed [evidence: neuropsychological assessment; confidence: emerging — extends MS-style cognitive profiling to T1DM]
• multimodal_biomarker_panel — feasible_for → autoimmune_disease [evidence: study design demonstrates feasibility across two diseases simultaneously; confidence: established]

Methods note

Cross-sectional case-control with two disease arms + healthy controls; total n=76 in main cohort, +12 in exploratory long-duration T1DM arm. Assessment stack: clinical/neuropsychological evaluation, peripheral cellular immune profiling, whole-brain and regional grey-matter volumetry (likely MPRAGE-MRI), OCT for peripapillary RNFL, serum NfL and GFAP via likely Simoa platform. Statistical approach not specified in abstract but typical for the design is between-group ANOVA / Kruskal-Wallis + within-disease correlation analysis.

Limitations

• Small per-group n (18 / 26 / 20) limits subgroup analysis power
• Newly-diagnosed cohorts may not capture later neurodegenerative trajectory
• T1DM neurological involvement remains contested; this study's finding of elevated sNfL in T1DM-newly-diagnosed needs replication
• Cross-sectional — no within-subject temporal trajectory
• Right-eye-only OCT presumably (typical practice); not specified in abstract

Open questions raised

• Q-Re-16 (new): Does FM show the same multimodal biomarker pattern (sNfL elevated + RNFL thinning) as MS, or a partially-overlapping pattern (e.g., sNfL elevated per Fundaun 2026 + RNFL thinning per Garcia-Martin 2016, but thalamic volume unchanged)? Direct multimodal comparison would partition FM along the neurodegenerative axis.
• Q-Re-17 (new): Is the FM-relevant comparator MS-RR (relapsing-remitting, immune-mediated) or T1DM (autoimmune-metabolic)? Answering this informs whether the FM autoimmune-subtype framing reads more like MS or more like T1DM at the biomarker level.
• Q-Re-18 (new): Can the protocol (RNFL + sNfL + GFAP + thalamic volumetry) be deployed as a multi-modal FM diagnostic panel? Cano-Cano demonstrates feasibility; the unanswered question is marginal-AUC contribution of each modality in FM specifically.

Triangulation notes

• Closes a methodology gap for B-Re-4 (Serum NfL ↔ retinal RNFL thinning, joint neural-injury biomarkers): supplies a cross-condition demonstration that the multimodal panel (sNfL + RNFL + GFAP + thalamic volume) is jointly measurable and discriminative across two autoimmune conditions. Direct template for an FM biomarker-mapping cohort.
• Supports B-Re-6 (Objective FM diagnostic biomarkers ↔ retinal imaging substrate): the García-Domínguez 2026 review surveys the aspirational landscape; this paper operationalizes a slice of that landscape in two non-FM autoimmune conditions. The retinal-biomarker priority document operationalizes the same slice for FM specifically.
• Reinforces choice of MS as cross-condition methodology comparator: Bandinelli 2025 used PASC-SFN as the cross-condition diagnostic-modality comparator for FM; Cano-Cano supplies MS as a second cross-condition comparator with overlapping methodology stack. PASC-SFN, MS, and FM converge on the same biomarker panel — methodological concordance across three conditions strengthens the cross-condition framing.
• Suggests T1DM as new bridge candidate: the finding that T1DM-newly-diagnosed shows elevated sNfL is novel and suggests T1DM may share the immune-mediated neurodegenerative axis with FM/MS. New candidate bridge B-Re-9 (T1DM ↔ FM via shared multimodal neurodegenerative panel) — bridging tier.

Bridges

• B-Re-9 (NEW candidate): Type 1 diabetes ↔ FM via shared multimodal neural-injury biomarker pattern (sNfL elevation + cognitive disturbance + immune-mediated framing). Confidence: bridging — predicts FM should resemble T1DM more than MS at the metabolic-autoimmune intersection. To document in synthesis/bridges.md.
• B-Re-4 strengthening: this paper supplies the empirical demonstration that the multimodal panel template works in autoimmune disease — increases confidence in B-Re-4 from "predicted" to "implementation-ready."