title: Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sjögren Syndrome with Negative Anti-SSA/SSB Antibodies.
abstract: We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology.
  
  
  
  The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion.
  
  
  
  There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased.
  
  
  
  The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hernández-Molina
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Carlos
authors.initials: C
authors.lastname: Nuñez-Alvarez
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Carmen
authors.initials: C
authors.lastname: Avila-Casado
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hernández-Hernández
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Calderillo
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Verónica
authors.initials: V
authors.lastname: Marroquín
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Claudia
authors.initials: C
authors.lastname: Recillas-Gispert
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto.
authors.forename: Juanita
authors.initials: J
authors.lastname: Romero-Díaz
authors.affiliation: From the Department of Immunology and Rheumatology, the Dental Service, and the Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Pathology, University Health Network, Toronto General Hospital, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.G. Hernández-Molina, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Nuñez-Alvarez, PhD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Avila-Casado, PhD, Department of Pathology, University Health Network, Toronto General Hospital, University of Toronto; L. Llorente, MD, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Hernández-Hernández, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; M.L. Calderillo, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; V. Marroquín, MD, Dental Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; C. Recillas-Gispert, MD, Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Romero-Díaz, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; J. Sánchez-Guerrero, MS, Mount Sinai Hospital and University Health Network, University of Toronto. JSanchez-Guerrero@mtsinai.on.ca.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sánchez-Guerrero
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008840:Microfilament Proteins / Q000276:immunology*; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood*; D012859:Sjogren's Syndrome / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D013049:Spectrin
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002352:Carrier Proteins; D007070:Immunoglobulin A; D008840:Microfilament Proteins; D012217:Rheumatoid Factor; D013049:Spectrin
keywords: ANTI-α-FODRIN ANTIBODIES; PRIMARY SJÖGREN SYNDROME