High activity of human cytomegalovirus in patients with Sjögren’s disease

In a cross-sectional observational study using immunohistochemistry and serology to assess human cytomegalovirus (HCMV) activity in salivary gland tissue and serum samples, Pantalone et al. (Karolinska Institutet, Stockholm; Turku University, Finland) — published in Clinical Immunology — investigated the presence and potential role of HCMV in patients with Sjögren’s disease (SD).

Their findings showed:

• SD patients had significantly higher expression of HCMV proteins in salivary gland tissue:
  1. HCMV-IE: 88.9%
  2. HCMV-LA: 69.2%
  3. HCMV-pp65: 45.8%
• HCMV-specific IgM was more frequent in SD patients than in controls (32.1% vs. 13.4%, p = 0.04)
• HCMV-IgG titers were significantly elevated in the SD group (p < 0.0001)

These results suggest a possible role of active or latent HCMV infection in the pathogenesis of Sjögren’s disease, although a causal relationship has not been established.

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While Sjögren’s disease is primarily a rheumatologic condition, this study provides important implications for neurosurgeons:

• The presence of active HCMV infection in autoimmune disease reinforces the hypothesis that viral latency and reactivation may be a cofactor in neuroinflammation, cognitive dysfunction, and chronic fatigue syndromes often seen in SD patients.

• Neurological manifestations of Sjögren’s include:
  1. Sensory and small-fiber neuropathies
  2. Trigeminal neuralgia
  3. Myelopathy or MS-like presentations
  4. Cognitive fog and mood changes

• Given the neurotropic potential of HCMV, this study supports further investigation into whether latent viral infections play a role in neuroimmune dysregulation, especially in patients with overlapping symptoms (e.g., unexplained neuropathies or cognitive decline).

• In neurosurgical patients with autoimmune backgrounds, especially those with unexplained CNS or PNS involvement, consider exploring viral serology (HCMV, EBV, HSV) as a potential contributor.

The authors repeatedly suggest a *pathogenic role* of HCMV in SD. But this is a cross-sectional observational study, making causal inference methodologically impossible. The presence of viral proteins or antibodies does not establish temporal or mechanistic causality.

→ *They detect smoke, then hypothesize arson, without checking for a fireplace.*

The serologic data are underwhelming:

• IgM: 32.1% in SD vs. 13.4% in controls (P=0.04)
• IgG: Higher titers in SD (P<0.0001)

But no viral DNA quantification (e.g., qPCR), no longitudinal viral kinetics, and no cytokine profiling were performed to support active reactivation or its functional relevance. → *This is viral presence by suggestion, not by demonstration.*

Several authors (e.g., Söderberg-Nauclér) have long promoted the role of HCMV in chronic diseases. This study reads like confirmation bias in action. The data are made to fit the theory, rather than challenge it.

→ *When you carry a viral hammer, every immune disease looks like a nail.*

While the inclusion of “Sicca but not SD” patients is commendable, the selection and matching criteria are unclear. Were comorbidities, age, immunosuppressive use, or HCMV exposure history balanced?

→ *Without proper matching, you’re comparing weather across cities with different climates.*

No treatment implications. No biomarker validated. No outcome tracked. Despite its title, the study offers no actionable insight for the diagnosis, management, or prevention of SD.

→ *It’s all noise and no signal — or worse, signal misinterpreted as insight.*

This study is scientifically decorative, not clinically transformative. It’s another installment in the long tradition of elegant immunohistochemistry papers that propose bold pathogenic hypotheses without adequate mechanistic or temporal evidence.

Clever staining. Careless thinking.