Abstract
Immunofluorescent imaging has been a powerful technique in helping to identify intracellular nuclear and cytoplasmic molecules which are target antigens of autoantibodies in systemic autoimmune disorders. Patterns of staining can be correlated with molecules engaged in specific cellular functions and distributed in distinct cellular domains. Different autoimmune disorders have different profiles of autoantibodies, and immunodiagnostics has become an important adjunct in differential diagnosis. An important finding that has eluded explanation is the presence of autoantibodies to many different antigens, manifested strikingly in systemic lupus erythematosus. In cancer, the occurrence of autoantibodies to tumor-associated antigens is not uncommon and a characteristic feature is also the presence of multiple autoantibodies. The targeted tumor-associated antigens are either oncogene or tumor suppressor gene products or their coactivators, which are altered or mutated and driving the autoimmune response. Most cancer cells have between two and eight mutated genes before oncogenic transformation occurs, initiating a process called synthetic lethality in tumorigenesis pathways. These observations beg the question of whether there are similar mechanisms in systemic lupus erythematosus and other disorders driving autoimmunity pathways. Targeting molecules that are synthetic lethal to each other is in the forefront of the search for anticancer therapy, and this could also be an objective in systemic autoimmune disorders.
Highlights
Antinuclear antibodies (ANAs) have been used for several decades as diagnostic biomarkers and are involved in autoantibody-mediated immune complex inflammation in the kidney, lung, brain, skin, joints and many other organs [1,2]
Many of the major nuclear and cytoplasmic components which are the target antigens of these autoantibodies have been identified, but the reasons why these cellular components acquired immunogenicity and induced autoantibody formation are largely unknown. Elucidation of this enigma is arising from studies of autoantibodies to tumorassociated antigens (TAAs) in cancer, suggesting that, in addition to their known roles in diagnosis and pathogenesis, ANAs might be revealing the cellular components involved in autoimmunity pathways in the way that autoantibodies to Tumor-associated antigen (TAA) inform on partners in tumorigenesis pathways
Subsequent studies have shown that this is a staining pattern characteristic of autoantibodies reacting with Sm antigen, a complex of small nuclear RNA and proteins called snRNPs, which are involved in the processing of precursor mRNAs to mature mRNAs [2]
Summary
Antinuclear antibodies (ANAs) have been used for several decades as diagnostic biomarkers and are involved in autoantibody-mediated immune complex inflammation in the kidney, lung, brain, skin, joints and many other organs [1,2]. The molecular targets of these novel autoantibodies were identified as insulin-like growth factors [4,5], coregulators of oncogenes [6,7], or tumor suppressor genes [8,9] Extension of such studies to other types of solid tumors showed frequent occurrence of autoantibodies to a number of cellular antigens that have been called TAAs. Other features include autoantibodies to multiple TAAs, with the majority of patients having two or more antibodies, a characteristic that recapitulates observations in systemic autoimmune diseases. Competing interests The author declares that he has no competing interests
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