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

Abstract

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.

Membrane attack complex (C5b‐9 complex or Mac), is strongly present in lesional skin from patients with endemic pemphigus foliaceus in El Bagre, Colombia

“…We documented that the immune response eventually becomes polyclonal, displaying autoreactivity directed toward epidermal keratinocytic intercellular junctions as well as the dermal‐epidermal BMZ, and the BMZs of dermal skin appendages. In addition, autoreactivity is noted against neurovascular supply cell junctions, and against multiple skin neural receptors . Other immunoglobulins and complement components such as IgM, IgE, IgD, complement/C1q, complement/C3c, complement/C4, and kappa and lambda light chains are seen, in addition to the previously reported IgG .…”

“…In addition, autoreactivity is noted against neurovascular supply cell junctions, and against multiple skin neural receptors. 18 Other immunoglobulins and complement components such as IgM, IgE, IgD, complement/C1q, complement/C3c, complement/C4, and kappa and lambda light chains are seen, in addition to the previously reported IgG. 7 Often weak ICS staining with IgG is observed in chronic cases.…”

“…In addition to this staining, other immunoglobulins and complement as well as deposits of fibrinogen and albumin are also seen targeting unique molecules in other parts of the skin. As reported previously, in about one‐third of the El Bagre‐EPF patients the immune response is directed not only to the skin, but also to several cell‐junction and neural receptors in most organs and tissues . The patients with a more extended percentage of compromised skin (according to Lund and Browder skin burn surface scale) show higher titers of serum autoantibodies as well as stronger reactivity to the complement/C5‐b9 antibody.…”

“…As reported previously, in about one-third of the El Bagre-EPF patients the immune response is directed not only to the skin, but also to several cell-junction and neural receptors in most organs and tissues. 18 The patients with a more extended percentage of compromised skin (according to Lund and Browder skin burn surface scale) 16 show higher titers of serum autoantibodies as well as stronger reactivity to the complement/C5-b9 antibody. This is indicative of epitope spreading and/or exposure to new autoantigens as shown by us 18 when the initial antibodies may damage the cell plasma membrane exposing internal cell molecules to the immune system.…”

“…18 The patients with a more extended percentage of compromised skin (according to Lund and Browder skin burn surface scale) 16 show higher titers of serum autoantibodies as well as stronger reactivity to the complement/C5-b9 antibody. This is indicative of epitope spreading and/or exposure to new autoantigens as shown by us 18 when the initial antibodies may damage the cell plasma membrane exposing internal cell molecules to the immune system. 19 The CS contains multiple plasma-and membrane-bound proteins and receptors working in the vanguard of host defense, killing pathogens, opsonizing and changing cells and microorganisms, and linking innate immunity to adaptive immune responses.…”