Autoantibodies against Components of Sensory Nerve Formations in the Intervertebral Disks and Adjacent Structures are Antigens Recognized by the Sera from Patients Affected by a New Variant of Endemic Pemphigus in El Bagre, Colombia

Abstract

Introduction: Patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia have autoantibodies directed against different proteins in the skin and internal organs. In this study we investigated autoantibodies in the intervertebral disk (IVD) and surrounding spinal structures since most patients suffer from back pain.

Methods: We tested autoreactivity using indirect immunofluorescence, reflectance, and confocal microscopy using patient autoantibodies, with both human and bovine tissue as antigen sources. We tested 45 sera from patients and 45 control sera from the endemic area matched by age, sex, demographics, and work activity. Additional mass bone density and trabecular bone score (TBS) were determined in selected cases.

Results: Most of the patient sera revealed polyclonal autoreactivity against previously known and new neural receptors present in the IVD (translamellar cross-bridges of the annulus fibrosus and the nucleus pulposus), neurovascular bundles, and paraspinal neurovascular packages as well as in the anterior and posterior longitudinal ligaments (P<0.001). Patient autoantibodies co-localized with commercial antibodies to MYZAP, desmoplakins I–II, plakophilin-4, and ARVCF (P<0.001). Controls were negative. Triton X-100 and paraformaldehyde allowed us to see the complex morphological 3-dimensional shape of the nerves and receptors. We also found that the patients showed altered microarchitecture of the lumbar spine and low trabecular density, thus suggesting osteoporosis and/or osteopenia.

Conclusions: The autoantibodies to neural receptors in the IVD and surrounding structures and the osteopenia may contribute to patient back pain. Also, El Bagre-EPF autoantibodies provide a new tool to study the complexity of these neural receptors.