Cross‐Reactions of Human Lupus Autoantibodies with 8‐Methoxypsoralen Photomodified DNA Fragments

Abstract

DNA fragments of around 200 base pair (average size) have been covalently crosslinked with 8‐methoxypsoralen under 365 nm UV light. The photoadduct, induced antibodies in rabbits with a titer of > 1:12,800 by direct bindng ELISA. Binding data showed that the induced antibodies are conformation‐specific recognizing restricted conformational change at site of crosslinking. Human autoantibodies against DNA, bound not only to native DNA but to the photomodified DNA fragment as well. In addition, binding patterns of SLE sera obtained from different patients were remarkably similar, indicating the recognition of altered conformation of the modified polymer by naturally occurring SLE anti‐DNA autoantibodies.

Immunological studies on DNA‐lysine photoadduct

“…The dynamic native DNA macromolecule is known to be a poor immunogen whose immunogenic form has not yet been identified. However, any perturbations in the DNA structure, a variety of synthetic analogus of DNA as well as its conformational variant and modified form of native DNA have been shown to be potent immunogen (22)(23)(24)(25)(26)(27). Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence ofhetrogeneous population of circulating antibodies to intracellular proteins and nucleic acids.…”

Neo-epitopes on crotonaldehyde modified DNA preferably recognize circulating autoantibodies in cancer patients

“…For more details, see Materials and methods section were placed dropwise on a mica wafer, air-dried at room temperature for 12 h, and the imaging was done with a Nanoscope II Atomic Force Microscope (Veeco Instruments, USA) using stiff AFM probes (RTESP Veeco, spring constant, k=21-98 N m −1 ; resonance frequency, f=146-236 kHz) in tapping mode at a scanning frequency of 1-3 Hz All these results point toward DNA modification and crosslinking by crotonaldehyde. Previous studies have shown that modification of DNA by furocoumarins and anticancer drugs like cisplatin causes crosslinking in DNA [39,40] and alterations in DNA structure resulted from photo-addition could cause antibody induction in various autoimmune diseases [41]. The crosslinking is one of the crucial steps for the generation of neo-epitopes on modified DNA.…”

Possible augmentation of photosensitivity by dietary furanocoumarins in patients with systemic lupus erythematosus

“…Photoadducts of DNA and 8-MOP have been found to cross-react with naturally occurring human anti-DNA autoantibodies, providing an additional mechanism for the induction of an SLE flare following increased FC intake. 39 The potential for FC-rich diets to enhance photosensitivity in patients with SLE has not been examined. There are scant data in the literature regarding FC intake in SLE patients, and the relation of a high-FC diet to photosensitization is less well documented.…”

“…Photoadducts of DNA and 8-MOP have been found to cross-react with naturally occurring human anti-DNA autoantibodies, providing an additional mechanism for the induction of an SLE flare following increased FC intake. 39…”