Targeting GzmB in maternal NK cells alleviates MIA-induced neuroimmune disorders

Plus diagnosis & Management of Atypical neuro-Inflammation

​​Val's Take/Conjecture

• We're getting a narrative that hangs together with respect to MIA-induced neuro-developmental and psychiatric disorders.
• Chinese researchers have made a big breakthrough.

Additionally, we need diagnosis and management of atypical neuro-inflammation across the lifespan.​

Moleculera Labs developed the Cunningham Panel to diagnose some auto-immune psychiatric disorders.

• ​The Cunningham Panel, now known as the Autoimmune Brain Panel, is often ordered through Neurology as opposed to Psychiatry.
• This is looking like a traditional medical approach with biomarkers.
• ​BUT not everyone has the auto-immune psychiatric disorders that the Cunningham Panel tests for.

That's one of the reasons why the paper Diagnosis and Management of Children With Atypical Neuroinflammation is so important. 

• Researchers are focusing more broadly on ATYPICAL NEURO-INFLAMMATION.

​Diagnosis and Management of Children With Atypical Neuroinflammation (2025)

Pediatric neuroimmune disorders comprise a heterogeneous group of immune-mediated CNS inflammatory conditions.

Some, such as multiple sclerosis, are well defined by validated diagnostic criteria.

Others, such as anti-NMDA receptor encephalitis, can be diagnosed with detection of specific autoantibodies.

This review addresses neuroimmune disorders that neither feature a diagnosis-defining autoantibody nor meet criteria for a distinct clinicopathologic entity.

A broad differential in these cases should include:
* CNS infection,
*noninflammatory genetic disorders,
*toxic exposures,
*metabolic disturbances, and
​*primary psychiatric disorders.

Neuroimmune considerations addressed in this review include:
* seronegative autoimmune encephalitis,
*seronegative demyelinating disorders such as neuromyelitis optica spectrum disorder, and
*genetic disorders of immune dysregulation or secondary neuroinflammation.

In such cases, we recommend a broad diagnostic workup:
* to support the presence of neuroinflammation,
* exclude non-neuroimmune disorders,
* detect autoantibodies and other biomarkers of known diseases,
* identify any potential genetic drivers of neuroinflammation, and
​*provide case-specific insights into pathophysiologic mechanisms of inappropriate immune pathway activation or dysregulation.

This review includes an extensive list of useful diagnostic tests and potential implications thereof, as well as a proposed algorithm for the diagnosis and management of the pediatric patient with atypical neuroimmune disorders

​Bullets added.

​Author Affiliations
​
1Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, CA.
2Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles.
3Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, United Kingdom.
4Department of Women and Children's Health, School of Life Course Sciences (SoLCS), King's College London, United Kingdom.
5Department of Neurology, Boston Children's Hospital, Harvard Medical School, MA.
6Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; and.
7Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom.

Maternal natural killer cells drive neuroimmune disorders in offspring through aberrant secretion of extracellular granzyme B (2025)

*China

​Highlights
•Stressed maternal NK [Natural Killer] cells drive activated macrophage accumulation in fetal brains
•CD49a+ trNK-derived GzmB promotes the propagation of immune signals in MIA [Maternal Immune Activation]
•Maternal GzmB induces ISGshi macrophage accumulation and microglial activation
•Targeting GzmB in maternal NK cells alleviates MIA-induced neuroimmune disorders

​Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we? (2024)