Clinical significance of antinuclear antibodies in malignant diseases: association with rheumatic and connective tissue paraneoplastic syndromes

Abstract

Our objective was to determine the prevalence of antinuclear antibodies (ANAs) in patients with malignancies and to investigate if their presence might be related with development of musculoskeletal symptoms or paraneoplastic rheumatic syndromes. Antinuclear antibodies were determined by indirect immunofluorescence on Hep-2 cells in 274 neoplastic patients and in a control group of 140 age-adjusted healthy subjects. Antinuclear antibody specificities (anti-DNA and anti-ENA) were investigated in patients with rheumatological symptoms and positive ANA. Antinuclear antibodies were detected in 76 of 274 (27.7%) patients with malignancies and in nine of 140 (6.4%) healthy subjects. Twenty patients reported paraneoplastic rheumatic symptoms or syndromes. Two of them developed clinical symptoms mimicking rheumatoid arthritis (rheumatoid-like arthropathy), one systemic lupus erythematosus (lupus-like syndrome), one dermatomyositis and four cutaneous vasculitides. Musculoskeletal symptoms and paraneoplastic rheumatic symptoms and syndromes were both more frequently observed in patients with positive ANA. Antinuclear antibody specificities were found in only two cases. We can conclude that there is an increased incidence of antinuclear antibodies in malignant conditions. Musculoskeletal symptoms and rheumatic paraneoplastic symptoms and syndromes seem to be more frequent in patients with cancer-related positive ANAs. The failure to find ANA specificities (anti-ENA, anti-DNA) in patients with malignancies and positive ANAs in our study may simply reflect molecular differences between the autoantigens involved in cancer and those characteristically involved in the systemic autoimmune diseases.

A case series of malignancies: mimics of Rheumatological disorders

“…ANA was positive in up to 27% cancer patients in one study and some of them had clinical picture similar to rheumatoid arthritis, SLE, autoimmune myositis, and cutaneous vasculitis etc. There are no known antibodies to ENA or double stranded DNA which points towards difference in autoantigens involvement in cancers and autoimmune diseases [1].…”

Detection of serum antinuclear antibodies in lymphoma patients

“…This may be mediated by antibody-dependent cell-mediated cytotoxicity (ADCC), by cytokines that enhance the immune function induced by ANA immune complexes, and by eliminating or reducing the inhibitory effect of extracellular chromatin on natural killer (NK) cell activity through the binding of ANAs and extracellular nuclear chromatin released from apoptotic tumor cells (Lu et al, 1998). Some cancer patients have been misdiagnosed in clinical situations owing to various serum autoantibodies and manifestations of rheumatism (Abu-Shakra et al, 2001;Solans-Laqué et al, 2004;Mu et al, 2006).…”

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

“…These antibodies, which bind to a variety of intracellular nuclear antigens, can also be present in healthy individuals, the elderly, those with thyroid disease, patients with active infections, and others (Kavanaugh, Tomar, Reveille, Solomon, & Homburger, 2000;Marin, Cardiel, Cornejo, & Viveros, 2009;Nilsson et al, 2006). Moreover, ANAs are often present in patients with malignancies, with a prevalence of 5-55%, depending on the particular cancer (Imran, Neelam, & Tariq, 2003;Kavanaugh et al, 2000;Solans-Laque et al, 2004). According to one recent study, even after a 1:80 dilution of serum, the prevalence of ANAs in healthy controls is 8% and more than 12% in those with multiple medical problems (Wichainun et al, 2013).…”