Blood Counts as Biomarkers? Haematologic Clues to Natalizumab Response in Multiple Sclerosis

Multiple Sclerosis (MS) treatment continues to evolve with the advent of high-efficacy disease-modifying therapies. One such therapy, natalizumab, a humanized monoclonal antibody, has significantly impacted how relapsing forms of MS are managed. But despite its clinical potency, questions remain: Can we predict which patients will respond best? Could routine blood tests help guide us?

A study presented as Poster P5.288 at the 2016 AAN Annual Meeting by McNicholas et al. offers intriguing insights. Their research suggests that common haematological parameters—specifically changes in peripheral blood cell counts—might serve as biomarkers of treatment response to natalizumab.

Natalizumab and Its Immunologic Footprint
Natalizumab exerts its effects by targeting α4 integrins (particularly α4β1 and α4β7) on the surface of leukocytes. By doing so, it blocks their adhesion to vascular cell adhesion molecule-1 (VCAM-1), thereby preventing their migration across the blood-brain barrier into the central nervous system (CNS). This mechanism reduces CNS inflammation, a key driver of MS pathogenesis.

However, this blockade doesn't just impact immune cell trafficking; it also alters the peripheral blood landscape. The hypothesis explored by McNicholas and colleagues is straightforward: Do these blood count changes correlate with clinical response?

Study Design and Patient Cohort
The team performed a retrospective audit on 113 patients with MS treated with natalizumab between 2006 and 2015. Importantly:

Complete blood counts (CBCs) were tracked prior to treatment and at 3-month intervals.

These results were correlated with both clinical and radiological measures of treatment response.

Key Haematologic Findings
Lymphocyte Counts: A Rising Trend
Mean increase: +1.02 x 10⁹/L within the first 3 months.

Elevated levels remained stable throughout treatment.

Lymphocytosis (defined as lymphocyte count >4 x 10⁹/L) was 3x more frequent in responders (31.7%) vs non-responders (10%).

Eosinophils and Monocytes: Subtler Signals
Eosinophil counts rose modestly (+0.18 x 10⁹/L). Monocyte counts showed a gradual increase over 9 months, suggesting longer-term haematopoietic modulation.

Atypical Lymphocytes: An Immunological Signature?
Found in 36.7% of responders, compared to 10% of non-responders.

Presence of these reactive forms may reflect a more activated or remodeled immune environment in responders.

Immature Cells in Peripheral Blood
Myeloid and lymphoid precursor cells were seen only in responders (except one non-responder with myelocytes).

These included plasmacytoid cells, potentially linked to interferon signaling and immune modulation.

Immunophenotyping Insights
One patient with lymphocytosis underwent flow cytometry: findings included B- and T-cell activation markers (CD38+, CD23+, FMC7+).

This suggests polyclonal immune activation, not malignancy.

What Does This Mean Clinically?
This study suggests that routine CBCs, often overlooked in their diagnostic potential, may be repurposed as low-cost, accessible biomarkers to gauge natalizumab response. Key takeaways include:

A rapid and sustained lymphocyte rise may indicate positive treatment effect.

Atypical lymphocytes and precursor cells may further differentiate responders from non-responders.

These markers are non-invasive and easily integrated into existing clinical workflows.

Importantly, no observed blood count changes raised concerns for hematologic malignancy—an important reassurance for clinicians monitoring patients on natalizumab.

Limitations and Future Directions
While these findings are promising, some caveats apply:

As a retrospective audit, causality cannot be definitively established.

Further prospective validation is needed, ideally with standardized response criteria and additional immune profiling.

Future work could investigate whether baseline haematologic profiles predict long-term response or risk of adverse events like PML (progressive multifocal leukoencephalopathy).

Conclusion
The immune system leaves signatures—not just in CNS lesions, but in the blood. This study by McNicholas et al. adds compelling evidence that haematologic changes can mirror therapeutic impact in MS patients treated with natalizumab.

For clinicians, this could mark a step toward personalized monitoring. For researchers, it highlights the need to delve deeper into the immunologic effects of monoclonal therapies beyond the CNS.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
McNicholas N, Kearney H, Krakar A, et al. Haematologic Modifications as Markers of Response to Treatment in Multiple Sclerosis Patients Treated with Natalizumab (P5.288). Neurology. 2016;86(16_Supplement). doi:10.1212/WNL.86.16_supplement.P5.288