Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is a tissue−specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin−1/2 (FLOT1/2) complex have been described in 1−2% of the patients in a recent study. Other candidate antigens as anoctamin−2 (ANO2) or neurofascin−155 (NF155) have been previously described in MS patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against NF155, ANO2 and the FLOT1/2 complex in MS. Serum (n=252) and CSF (n=50) samples from 282 MS patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti−FLOT1/2, anti−ANO2 and anti−NF155 antibodies were tested by cell-based assays using transfected−HEK293 cells. We identified 6 MS patients with antibodies against the FLOT1/2 complex (2.1%) and 1 MS patient with antibodies against ANO2 (0.35%). All MS patients were negative for anti−NF155 antibodies. Three of the anti−FLOT1/2 positive patients showed anti−FLOT1/2 positivity in other serum samples extracted at different moments of their disease. IgG subclasses of anti−FLOT1/2 antibodies were predominantly IgG1 and IgG3. We confirm that antibodies targeting the Flotillin1/2 complex are present in a subgroup of patients with MS. Further studies are needed to understand the clinical and pathological relevance of anti−FLOT1/2 autoantibodies in MS.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by Roche Spain. MCA was supported by a personal Rio Hortega grant CM21/00101. LMA was supported by a personal Juan Rodes grant JR21/00060.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics commitee of Hospital de la Santa Creu i Sant Pau gave ethical approval for this work.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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