title: Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years.
abstract: The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43±13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58±13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥1:160 (HR 14.19, 95% CI 3.07-65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75-1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94-2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; University of Milan, Milan, Italy. Electronic address: carlo.selmi@unimi.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; University of Milan, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ceribelli
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Generali
authors.affiliation: Epidemiology Unit, Italian Society for Rheumatology (SIR), Milan, Italy.
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Scirè
authors.affiliation: Bergamo local health authority (ASL), Bergamo, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Alborghetti
authors.affiliation: Division of Internal Medicine, San Pietro Hospital, Ponte San Pietro, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Colloredo
authors.affiliation: Bergamo local health authority (ASL), Bergamo, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Porrati
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Maria I S
authors.initials: MI
authors.lastname: Achenza
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavaciocchi
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Massarotti
authors.affiliation: Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Natasa
authors.initials: N
authors.lastname: Isailovic
authors.affiliation: Clinical Research Unit, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Paleari
authors.affiliation: Center of Autoimmune Liver Disease, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Aesku Diagnostics, Wendelsheim, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Matthias
authors.affiliation: Bergamo local health authority (ASL), Bergamo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zucchi
authors.affiliation: University of Milan, Milan, Italy; Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
mesh_terms: D017677:Age Distribution; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D034961:Antigens, Nuclear / Q000097:blood* / Q000276:immunology; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D015995:Prevalence; D012727:Sex Characteristics
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear
keywords: Age; Autoimmunity; Cancer; Clinical epidemiology; Connective tissue disease; Gender; Survival