Autoreactive IgG antibodies in fibromyalgia: relation to symptom severity and pathophysiological mechanisms.

Recently, we reported autoreactive IgG antibodies (FM IgG) in fibromyalgia (FM) patients.

The overarching aim of this clinical study is to investigate how FM IgGs are related to symptoms and pathophysiological mechanisms. We profit from our new method to quantify FM IgG.

First, in an existing cohort, associations between FM IgG levels and symptom severity are determined and related to proteomics, metabolomics and lipidomics.

Second, associations between FM IgG and previously reported FM-related structural and functional pathology of C fibers as well as the newly discovered ultra-fast conducting A fibers (A-HTMRs) will be studied using skin biopsies and microneurography.

Finally, given neuroinflammation and cerebral glia activation in FM, potential FM IgG related CNS mechanisms will be examined by assessing blood-brain-barrier integrity (DCE-MRI), cerebrospinal fluid (CSF) IgG concentrations and intrathecal IgG production (IgG index).

These findings will be analyzed in relation to neuroinflammation (proinflammatory substances in CSF) and sleep disturbance (polysomnography).

The project is a collaboration between 3 Swedish universities, with subjects (n =300) recruited in Stockholm and Uppsala in 2023-25 and meta-data analysis with drafting of manuscripts in 2026-27.

The research will fundamentally improve our understanding of FM and facilitate development of objective diagnostic tools, use of immunomodulatory treatments and development of totally new biological treatments.