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Anti-Tr/DNER antibody–associated cerebellar ataxia: three rare cases report and literature review

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Abstract

Background

To report three cases of autoimmune cerebellar ataxia related to anti-delta/notch-like epidermal growth factor-related receptor (Tr/DNER) antibodies.

Case presentation

Patients with unknown cerebellar ataxia were screened with autoimmune cerebellar ataxia (ACA)-related antibody panel. The anti-Tr antibody was positive in three female patients in whom the onset ages were 43 years, 35 years and 43 years old. The antibody titres of serum and cerebrospinal fluid were all 1:32. Cerebral ataxia was the most prominent presentation. Mild cerebellar atrophy was found in one of the patients. Immunotherapy was effective in all three patients.

Conclusion

The Tr antibody is associated with autoimmune ataxia, and it has been suggested that the anti-Tr antibody should be tested in patients with cerebellar ataxia who are negative for routine ACA antibodies. Early immunotherapy may improve patient prognoses.

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Data availability

All the data generated or analysed during this study are included in this published article.

Abbreviations

Tr/DNER :

Anti-delta/notch-like epidermal growth factor-related receptor

ACA :

Autoimmune cerebellar ataxia

Homer-3 :

Homer protein homologue 3

PCA-2 :

Purkinje cell antibody 2

VGCC :

Voltage-gated calcium channel

mGluR1 :

Metabolic glutamic acid receptor 1

TRIM9 :

Tripartite motif−containing 9

NMDAR :

N−methyl−D−aspartate receptor

LGI1 :

Leucine−rich glioma inactivated−1

GABAR :

Gamma−aminobutyric acid receptor

CASPR2 :

Contactin−associated protein like 2

AMPAR1 :

α−Amino− 3−hydroxy−5−methyl−4−isoxazolepropionic acid receptor 1

AMPAR2 :

α−Amino−3−hydroxy−5−methyl−4−isoxazolepropionic acid receptor 2

DPPX :

Dipeptidyl−pepti dase−like protein−6

GAD65 :

Glutamic acid decarboxylase 65

ZIC4 :

Zinc finger protein 4

ITPR1 :

Inositol 1, 4, 5−trisphosphate receptor 1

NCDN :

Neurochondrin

PCA−2 :

Purkinje cell antibody 2

CARPVII :

Carbonic anhydrase−related protein VII

TBA :

Tissue-based assay

CBA :

Cell-based assay

FITC :

Fluorescein isothiocyanate

PBS :

Phosphate buffer saline

CSF :

Cerebrospinal fluid

MRI :

Magnetic resonance imaging

MRA :

Magnetic resonance angiography

CT :

Computed tomography

OB :

Oligoclonal band

SOB :

Serum oligoclonal band

mRS :

Modified Rankin Scale

MP :

Methylprednisolone

MBP :

Myelin basic protein

VEP :

Visual evoked potential

HD :

Hodgkin’s disease

PCD :

Paraneoplastic cerebellar degeneration

IVIG :

Intravenous immune globulin

MMF :

Mycophenolate mofetil

IHC :

Immunohistochemistry

PC :

Purkinje cell

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Funding

The authors acknowledge the support of Hebei Natural Science Foundation Precision Medicine Joint Project (Grant No. H2020201206) and the Central Government Guided Local Science and Technology Development fund project of Hebei Province (Grant No. 216Z7711G).

Author information

Author notes

  1. Yun Cai and Jie Liu contributed equally to this work as co-first authors.

  2. Hongzhi Guan and Weiying Di contributed equally to this work as co-corresponding authors.

Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Hebei University, Baoding, 071000, China

    Yun Cai, Fuping Shi, Jing Che, Qiang Geng & Weiying Di

  2. Department of Neurology, People’s Hospital of Sichuan Province, Chengdu, 610072, China

    Jie Liu

  3. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Haitao Ren & Hongzhi Guan

  4. Department of Pathology, Affiliated Hospital of Hebei University, Baoding, 071000, China

    Yanli Tan

Authors
  1. Yun Cai
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  2. Jie Liu
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  3. Haitao Ren
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  4. Fuping Shi
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  6. Qiang Geng
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  7. Yanli Tan
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Contributions

Weiying Di, Hongzhi Guan, Yun Caib and Jie Liu wrote the main manuscript text. Haitao Ren prepared Figs. 1–2. Fuping Shi, Jing Che and Qiang Geng compiled the case files. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongzhi Guan or Weiying Di.

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Ethical approval

This study was approved by the Medical Ethics Committee of Peking Union Medical College Hospital.

Informed consent

Written informed consents were obtained from the legal guardians of the patients.

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Written informed consents to publish this information were obtained from the patients and their legal guardians.

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The authors declare no competing interests.

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Cai, Y., Liu, J., Ren, H. et al. Anti-Tr/DNER antibody–associated cerebellar ataxia: three rare cases report and literature review. Neurol Sci 44, 397–403 (2023). https://doi.org/10.1007/s10072-022-06389-x

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  • DOI: https://doi.org/10.1007/s10072-022-06389-x

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