Neural System Antigens Are Recognized by Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia

Abstract

Background Endemic pemphigus foliaceus (EPF), is also known as “fogo selvagem” or “wild fire,” reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). Methods We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens. Results We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p<0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy. Conclusions Our findings may explain for the first time the “pose of pemphigus,” representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the “burning sensation” encountered in EPF disease.

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

“…We also utilized 15 control skin biopsies from cosmetic surgery patients in the USA, taken from the chest and/or abdomen. The Bagre-EPF patients were previously diagnosed by us, fulfilling specific criteria as previously documented [6][7][8][9][10]. We also tested another group of ABD patients, whose skin biopsies were obtained from the archival files of two private dermatopathology laboratories in the USA.…”

“…The organs from the autopsies were taken within 12 hours of patient death. The direct immunofluoresecent studies (DIF) were performed as previously described [6][7][8][9][10].…”

“…Performed as previously described [10]. In brief, postembedding immunogold labeling was performed on samples of El Bagre-EPF sera and controls.…”

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

“…We tested 30 biopsies from patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF); diagnostic criteria were followed as previously described [8][9][10]. We also tested skin biopsies from 30 controls from the El Bagre EPF endemic area, and 30 additional control skin samples from cosmetic surgery patients in the USA, taken from the chest and/or abdomen.…”

Merkel cell carcinoma versus metastatic small cell primary bronchogenic carcinoma

“…Our H & E staining and IHC studies were performed as previously reported [56][57][58][59][60]. For IHC, we utilized the following antibodies: monoclonal mouse anti-human TTF-1, insulin-like growth factor II mRNA binding protein 3 (IMP3), ribosomal protein S6-pS240/phosphorylation site specific, serotonin, survivin, synaptophysin, bromodeoxyuridine, tissue inhibitor of metalloproteinases 1 (TIMP-1), CK20, NSE, neurofilament protein, cyclo-oxygenase enzyme 2 (COX-2), Cyclin D1, CD56/NCAM, Chromogranin A (CgA), calretinin, epithelial membrane antigen (EMA/CD227), Ber-EP4, pancytokeratin (clone AE1/AE3), proliferating cell nuclear antigen (PCNA), MIC2 and Ewing's sarcoma marker (CD99).…”