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. 2023 Mar 15;12(3):e1439.
doi: 10.1002/cti2.1439. eCollection 2023.

Cerebrospinal fluid YKL-40 level evolution is associated with autoimmune encephalitis remission

Guillaume Dorcet  1   2   3 , Marie Benaiteau  1 , Jérémie Pariente  1   4 , Fabienne Ory-Magne  1 , Emmanuel Cheuret  5 , Marie Rafiq  1   4 , Wesley Brooks  6 , Bénédicte Puissant-Lubrano  2   3 , Françoise Fortenfant  2 , Yves Renaudineau  2   3 , Chloé Bost  2   3
Affiliations

Cerebrospinal fluid YKL-40 level evolution is associated with autoimmune encephalitis remission

Guillaume Dorcet et al. Clin Transl Immunology. .

Abstract

Objective: Because of its heterogeneity in clinical presentation and course, predicting autoimmune encephalitis (AIE) evolution remains challenging. Hence, our aim was to explore the correlation of several biomarkers with the clinical course of disease.

Methods: Thirty-seven cases of AIE were selected retrospectively and divided into active (N = 9), improved (N = 12) and remission (N = 16) AIE according to their disease evolution. Nine proteins were tested in both serum and cerebrospinal fluid (CSF) at diagnosis (T0) and during the follow-up (T1), in particular activated MMP-9 (MMP-9A) and YKL-40 (or chitinase 3-like 1).

Results: From diagnosis to revaluation, AIE remission was associated with decreased YKL-40 and MMP-9A levels in the CSF, and with decreased NfL and NfH levels in the serum. The changes in YKL-40 concentrations in the CSF were associated with (1) still active AIE when increasing >10% (P-value = 0.0093); (2) partial improvement or remission when the changes were between +9% and -20% (P-value = 0.0173); and remission with a reduction > -20% (P-value = 0.0072; overall difference between the three groups: P-value = 0.0088). At T1, the CSF YKL-40 levels were significantly decreased between active and improved as well as improved and remission AIE groups but with no calculable threshold because of patient heterogeneity.

Conclusion: The concentration of YKL-40, a cytokine-like proinflammatory protein produced by glial cells, is correlated in the CSF with the clinical course of AIE. Its introduction as a biomarker may assist in following disease activity and in evaluating therapeutic response.

Keywords: YKL‐40; autoimmune encephalitis; biomarker; neuroimmunology; neuroinflammation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Levels of YKL‐40 (a‐c), MMP‐9A (d‐f), α‐SYN (g‐i), neurofilament light (j–l) and heavy chains (m–o) (NfL and NfH) in serum and CSF from healthy donors (n = 5), Alzheimer's disease (n = 5) and AIE (n = 37) explored at diagnosis (T0) and during their follow‐up (T1), according to the diseases' activity. Each dot represents a sample. For α‐SYN in the Alzheimer's and Healthy donors' groups, almost all samples are above the range; they were represented at the detectable maximum of 100 000 pg mL−1 (broken line). Results from one experiment. Statistical analysis: Kruskal–Wallis' test for overall comparisons (bars without bracket), Wilcoxon's and Mann–Whitney's U‐tests for one‐to‐one groups comparison (bars with brackets, T0–T1 and between subgroups at T1, respectively). Bars show mean concentration with standard deviation. No comparison was performed between control groups (Alzheimer's and Healthy donors' groups) and AIE group at T0. AIE, autoimmune encephalitis; ns, nonsignificant. *P‐value ≤ 0.05, **P‐value ≤ 0.01, ***P‐value ≤ 0.001, ****P‐value ≤ 0.0001.
Figure 2
Figure 2
Longitudinal, individual variations between T0 and T1 of proteins having shown the strongest differences in the CSF at the group level (N = 18 cases). YKL‐40 (a) and MMP‐9A (b) in CSF, according to the course of the disease. Black dots represent patients' samples at T0. Coloured dots represent each patient's sample at T1. Results from one experiment. Statistical analysis: Kruskal–Wallis's test. AIE, autoimmune encephalitis.
Figure 3
Figure 3
Examples of longitudinal evolutions of YKL‐40 (a‐d) and MMP‐9A (e‐h) in the CSF of four cases. CTC, corticosteroids; CYC, cyclophosphamide; H, hospitalisation; IVIG, intravenous immunoglobulins; RTX, rituximab. T0–T1 delays were 1 month for patient #35 (anti‐CV2) and 3 months for cases #18 (anti‐IgLON5), 26 (anti‐NMDAR) and 24 (anti‐GFAP); T1–T2 delays were 3 months for cases #26, 6 months for patient #18, 9 months for patient #29 and 12 months for patient #35.
Figure 4
Figure 4
Main evolutionary modes of autoimmune encephalitis (AIE) in which the use of biomarkers would be helpful. In situation (a), the diagnosis of remission is false, leading to an unsuitable interruption of the immunotherapy. A relapse occurred soon after, raising the question of how to identify the still active inflammation to avoid the immunotherapy interruption. In situation (b), the patient has sequelae, which could be initially identified as a still active inflammation, leading to the prolongation of the immunotherapy. That raises the question of how to reach an earlier diagnosis of remission. On the contrary, in situation (c), the AIE course is extremely slow despite strong immunosuppression, with the risk of misdiagnosing sequelae and interrupting the immunotherapy too soon.
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References

    1. Graus F, Titulaer MJ, Balu R et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15: 391–404. - PMC - PubMed
    1. Dalmau J, Armangué T, Planagumà J et al. An update on anti‐NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models. Lancet Neurol 2019; 18: 1045–1057. - PubMed
    1. Armangue T, Spatola M, Vlagea A et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 2018; 17: 760–772. - PMC - PubMed
    1. Vogrig A, Muñiz‐Castrillo S, Desestret V, Joubert B, Honnorat J. Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord 2020; 13: 1756286420932797. - PMC - PubMed
    1. Chefdeville A, Honnorat J, Hampe CS, Desestret V. Neuronal central nervous system syndromes probably mediated by autoantibodies. Eur J Neurosci 2016; 43: 1535–1552. - PMC - PubMed
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