Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1–2 and ARVCF, causing renal damage

• Published in: Clinical and experimental dermatology Vol. 43; no. 6; pp. 692 - 702
• Main Authors: Abreu‐Velez, A. M., Howard, M. S., Yi, H., Florez‐Vargas, A. A.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2018
• Subjects: Autoantibodies; Autoimmune diseases; Autopsy; Bagre; Confocal microscopy; Creatinine; Demography; Electron microscopy; Glomerulonephritis; Immunoblotting; Immunofluorescence; Immunohistochemistry; Kidneys; Lupus nephritis; Microscopy; Myocardium; Nephritis; Pemphigus; Proximal tubules; Skin; Urea
• ISSN: 0307-6938; 1365-2230
• DOI: 10.1111/ced.13566

Summary Background We have previously reported that about 30% of patients affected by a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia (termed El Bagre‐EPF or pemphigus Abreu–Manu) have systemic compromise. In the current study, we focused on studying autoreactivity to the kidney and its pathological correlations. Aim To investigate patients with El Bagre‐EPF for renal compromise. Methods We performed a case–control study, enrolling 57 patients with El Bagre‐EPF and 57 controls from the endemic area, matched by age, sex, race, work activity, demographics and comorbidities. We took skin and renal biopsies; performed direct and indirect immunofluorescence, immunohistochemistry (IHC), confocal microscopy, immunoblotting, direct and indirect immune electron microscopy; and tested kidney function in all living patients. We also used IHC to study seven kidney autopsy samples. Results Of the 57 patients, 19 had autoantibodies to kidney, with polyclonal reactivity (P < 0.01). Most cases were positive along the basement membrane of the proximal tubules, but in some cases there was also positivity against the glomeruli and/or mixed patterns. Fifteen patients had increases in serum urea and creatinine compared with controls (P < 0.01). The autoantibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo–cardio–facial syndrome (ARCVF) and myocardium‐enriched zonula occludens‐1‐associated protein (MYZAP) (P < 0.01). All of the kidney disease autopsies showed alterations, mostly in the vessels. Conclusion We demonstrate for the first time that one‐third of patients with El Bagre‐EPF have polyclonal autoantibodies to kidney. The kidneys showed a mixed histological pattern resembling lupus nephritis, with a diffuse proliferative Class IV (G) global diffuse pattern in active lesions, and additional interposition of membranoproliferative glomerulonephritis.