New complex cell junctions in and around the intervertebral discs discovered using autoantibodies from patients affected by endemic pemphigus foliaceus in El Bagre, Colombia, South America

Ana Maria Abreu Velez; Takashi Hashimoto; Jorge Mario Vélez Arango; Yulieth Alexandra Upegui-Zapata; Eduardo Upegui-Quiceño; Adriana Milena Olarte Aponte; Michael S Howard

doi:10.1111/ijd.17471

New complex cell junctions in and around the intervertebral discs discovered using autoantibodies from patients affected by endemic pemphigus foliaceus in El Bagre, Colombia, South America

Int J Dermatol. 2024 Sep 15. doi: 10.1111/ijd.17471. Online ahead of print.

Authors

Ana Maria Abreu Velez¹, Takashi Hashimoto², Jorge Mario Vélez Arango³, Yulieth Alexandra Upegui-Zapata⁴, Eduardo Upegui-Quiceño⁵, Adriana Milena Olarte Aponte⁶, Michael S Howard¹

Affiliations

¹ Georgia Dermatopathology Associates, Atlanta, GA, USA.
² Department of Dermatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
³ SURA Diagnostic Aids, Research Group on Images & AI in Health, Bogota, Colombia.
⁴ Research Group on Infections and Health in the Tropics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia.
⁵ Program of Study and Control of Tropical Diseases (PECET) Universidad de Antioquia, Medellin, Antioquia, Colombia.
⁶ Program in Basic Sciences, Universidad Colegio Mayor de Cundinamarca (UCMC), Bogotá, Colombia.

PMID: 39279034
DOI: 10.1111/ijd.17471

Abstract

Background: Traditionally, the intervertebral disks' (IVD) nucleus pulposus (NP) and annulus fibrosus (AF) are considered to have few cellular components and cell junctions. Patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, experience back pain in the spinal areas of the lower and upper back. Here, we investigate the reactivity of the patient's autoantibodies to structures in and around the IVDs at the cellular level.

Methods: We first administered a questionnaire and performed a medical examination. We then tested for autoreactivity against IVDs by indirect immunofluorescence, confocal microscopy, and reflectance confocal microscopy using bovine and human tissues as antigen sources. We tested 45 sera from patients affected by the disease and 45 control sera from the endemic area matched by age, gender, demographics, and work activity.

Results: Most of the patient sera revealed polyclonal antibodies against newly discovered cell junctions in the NP and AF, including their translamellar cross-bridges. Additional reactivities were detected against cell junctions in the spinal cord neurons, paraspinal nerves, blood vessels, anterior and posterior longitudinal ligaments, and paraspinal skeletal muscles. The reactivities of the patient's autoantibodies co-localized with those of commercially available antibodies to desmoplakins I-II, armadillo repeat gene deleted in velo-cardio-facial syndrome, plakophilin-4, and myocardium-enriched zonula occludens-1-associated protein (p < 0.001).

Conclusions: We discovered novel complex cell junctions in the IVDs using patients' autoantibodies. These discoveries open a new chapter in the knowledge of IVD, representing a breakthrough pertinent to many diseases.

Keywords: ARCVF; MYZAP; annulus fibrosus; anterior and posterior longitudinal ligaments; autoimmunity; cell junctions; desmoplakins I and II; endemic pemphigus foliaceus; intervertebral disks; nucleus pulposus; p0071; paraspinal muscles; receptors.

Abstract

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