title: Anti-lactoferrin antibodies in systemic lupus erythematosus: isotypes and clinical correlates.
abstract: Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity (p = 0.017), anti-dsDNA (0.04), and anticardiolipin antibodies (p = 0.02) and were associated with Raynaud's phenomenon (p = 0.028), renal involvement (p = 0.007), serositis (p = 0.026), and history of thrombosis (p = 0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role.
authors.affiliation: Department of Clinical Medicine, Immunology, and Infectious Diseases, University of Bari, Policlinico, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Caccavo
authors.forename: Amelia
authors.initials: A
authors.lastname: Rigon
authors.forename: Antonio
authors.initials: A
authors.lastname: Picardi
authors.forename: Sara
authors.initials: S
authors.lastname: Galluzzo
authors.forename: Marta
authors.initials: M
authors.lastname: Vadacca
authors.forename: Giovanni Maria
authors.initials: GM
authors.lastname: Ferri
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Antonella
authors.initials: A
authors.lastname: Afeltra
mesh_terms: D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology*; D007781:Lactoferrin / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D007781:Lactoferrin