JNNP: Characterization of TRIM46 Autoantibody-Associated Nervous System Paraneoplastic Syndromes

The study initially described a triple motif-containing protein 46 (TRIM46) IgG staining pattern in a patient with paraneoplastic encephalomyelitis and small cell lung cancer
(SCLC) .
Autoantigens were later identified using immunoprecipitation

mass spectrometry .

Lung cancer immunity Article published in Journal of Neurology, Neurosurgery & Psychiatry Article published in Journal of Neurology, Neurosurgery & Psychiatry Psychiatry ) This article was published in the Journal of Neurology, Neurosurgery & Psychiatry

The Mayo Clinic Institutional Review Board approved a retrospective review of patient records and human specimen collection

.

TRIM46 was identified as an autoantigen

Unique immunofluorescence pattern of patient IgG binding to mouse tissue, confirming triple motif-containing protein 46 (TRIM46) as the target antigen 

TRIM46 immunoreactivity was assessed in formalin-fixed, paraffin-embedded 5 μm thick sections of breast adenocarcinoma tissue

.

Subacute cerebellar syndrome was present in 15 patients (68%), 6 isolated, and 9 had other signs: encephalopathy (4, 1 additional autonomic dysfunction, 1 opsoclonus-myoclonus) , brainstem signs (2), Parkinson's syndrome and dystonia ( 1), myelopathy (2, one was lower extremity hyperreflexia and bladder dysfunction, and the other was bilateral lower extremity weakness)
.
Three other patients developed limbic encephalitis

.

Tension Brain MRI was available in 16 patients and abnormal in 8

Expression of tripartite motif-containing protein 46 (TRIM46) in breast cancer tissues

breast cancer

 

Cancer was diagnosed in 18 patients (82%) , 8 of whom had metastatic disease (no CNS metastases)

.

Cancer was diagnosed in 18 patients (82%) , 8 of whom had metastatic disease (no CNS metastases)

In addition to the above post-ICI cases, 14 patients received immunosuppression: oral or intravenous methylprednisolone (8 patients), intravenous immunoglobulin (9 patients), plasmapheresis (3 patients), rituximab (1 case) and cyclophosphamide (1 case)
.
Of the 12 patients with available post-treatment follow-up data, none had significant neurological improvement

.

Of the 12 patients with available post-treatment follow-up data, none had significant neurological improvement

TRIM46-IgG should qualify as a high-risk paraneoplastic autoantibody, validated to be a strong predictor of underlying cancer
.
6 Testing for TRIM46-IgG should be considered in patients presenting with an intermediate or high-risk PNS phenotype,6 especially in subacute progressive cerebellar ataxia
.
TRIM46-IgG should qualify as a high-risk paraneoplastic autoantibody, validated to be a strong predictor of underlying cancer
.
6 Testing for TRIM46-IgG should be considered in patients presenting with an intermediate or high-risk PNS phenotype,6 especially in subacute progressive cerebellar ataxia
.
Valencia-SanchezC ,KnightAM ,HammamiMB Valencia-SanchezC Valencia-Sanchez KnightAM Knight HammamiMB Hammami , et al Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome Journal of Neurology, Neurosurgery & PsychiatryPublished Online First:17 December 2021.
 Published Online First: doi:10.
1136/jnnp-2021-326656 doi: leave a message here