Editorial Overview: Antinuclear Antibody- and Extractable Nuclear Antigen-Related Diseases

Abstract

In 1948, the observation of the LE cell phenomenon in a patient with systemic lupus erythematosus (SLE) began the discovery of a broad variety of autoantibodies directed to nuclear antigens called antinuclear antibodies (ANA). Nowadays, different ANA serve as important diagnostic parameters for differentiating most of the connective tissue diseases, such as SLE, neonatal lupus syndromes, Sjögren’s syndrome, scleroderma, autoimmune myositis, mixed connective tissue disease and other overlaps. This overview summarizes the history of ANA and their detection methods, in part to introduce the subsequent papers dealing with special topics of ANA-related diseases in this issue. Furthermore, the pathogenic role of these autoantibodies in targeting non-organ-specific intracellular antigens as a functional important constituent of a subcellular particle or multimolecular complex is addressed. Notably, some of these autoantibodies have functioned as significant tools for cell biologists to elucidate the subcellular structures and functions of these autoantigens. In the future, we can expect further advances to answer such important questions as why these antigens are targets of autoantibodies, what is their pathogenic impact and what are the triggers of autoimmunity?

Properties of Uncommon Indirect Immunofluorescence Staining Patterns Determined during Antinuclear Antibody Detection on HEp-2 Cells

“…Their assessment is one of the crucial steps in the evaluation and diagnostic workup of patients with systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE) (where the presence of ANA at any point in the disease serves as an entry criterion for diagnosis) [3][4][5], Sjögren's syndrome [6,7], systemic sclerosis [8], dermatomyositis/polimyositis [9] and others. Historically, those antibodies were thought of as effectors involved in the pathogenetic processes involved in the genesis of autoimmune rheumatic diseases [10], but later it has been hypothesised that they are in many cases an epiphenomenon of the disease, caused by elevated exposure of intracellular antigens to the immune system due to enhanced or aberrant apoptotic processes, or delayed elimination of those antigens from the system [11].…”

Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus

“…Available data suggest that the autoimmune response is antigen driven [111], and the consequences of the neo-antigenicity of the “altered self” [112] in genetically disease-prone individuals [113] must be taken into account, especially in patients relapsing after allo-HSCT. A treatment founded on gene therapy-assisted autologous HSC transplantation, with the object of achieving antigen-specific tolerance, is being actively pursued by Alderuccio et al [114].…”

Antigen Preparation for Immunological Studies in Systemic Autoimmune Diseases

“…Candidate autoantigens in systemic autoimmune diseases are ubiquitary, located on the plasma membrane (i.e., β2‐glycoprotein I), in the nucleus, such as DNA or nuclear proteins (i.e., histones, nucleosomes, Ku, Scl‐70), and in the cytoplasm (i.e., ribosomal P proteins) 16 . Nucleic acid–protein complexes located either in the nucleus or in the cytoplasm (i.e., snRNPs, tRNA synthetases, Ro/SSA, and La/SSB) are target autoantigens as well 16 …”