Serum lipid antibodies are associated with cerebral tissue damage in multiple sclerosis

血清脂质抗体与多发性硬化症的脑组织损伤有关

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作者:Rohit Bakshi, Ada Yeste, Bonny Patel, Shahamat Tauhid, Subhash Tummala, Roya Rahbari, Renxin Chu, Keren Regev, Pia Kivisäkk, Howard L Weiner, Francisco J Quintana

Conclusions

We propose serum antibody repertoires that are associated with MRI measures of cerebral MS involvement. Such antibodies may serve as biomarkers for monitoring disease pathology and progression.

Methods

In this cross-sectional study, serum samples were obtained from patients with relapsing-remitting MS (n = 21) and assayed using antigen arrays that contained 420 antigens including CNS-related autoantigens, lipids, and heat shock proteins. Normalized compartment-specific global brain volumes were obtained from 3-tesla MRI as surrogates of atrophy, including gray matter fraction (GMF), white matter fraction (WMF), and total brain parenchymal fraction (BPF). Total brain T2 hyperintense lesion volume (T2LV) was quantified from fluid-attenuated inversion recovery images.

Objective

To determine whether peripheral immune responses as measured by serum antigen arrays are linked to cerebral MRI measures of disease severity in multiple sclerosis (MS).

Results

We found serum antibody patterns uniquely correlated with BPF, GMF, WMF, and T2LV. Furthermore, we identified immune signatures linked to MRI markers of neurodegeneration (BPF, GMF, WMF) that differentiated those linked to T2LV. Each MRI measure was correlated with a specific set of antibodies. Strikingly, immunoglobulin G (IgG) antibodies to lipids were linked to brain MRI measures. Based on the association between IgG antibody reactivity and each unique MRI measure, we developed a lipid index. This comprised the reactivity directed against all of the lipids associated with each specific MRI measure. We validated these findings in an additional independent set of patients with MS (n = 14) and detected a similar trend for the correlations between BPF, GMF, and T2LV vs their respective lipid indexes. Conclusions: We propose serum antibody repertoires that are associated with MRI measures of cerebral MS involvement. Such antibodies may serve as biomarkers for monitoring disease pathology and progression.

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