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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.
J Rheumatol. 2016 10; 43(10):1852-1857.JR

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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+Show Affiliations

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.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.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.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.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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27481899

Citation

Hernández-Molina, Gabriela, et al. "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." The Journal of Rheumatology, vol. 43, no. 10, 2016, pp. 1852-1857.
Hernández-Molina G, Nuñez-Alvarez C, Avila-Casado C, et al. 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. J Rheumatol. 2016;43(10):1852-1857.
Hernández-Molina, G., Nuñez-Alvarez, C., Avila-Casado, C., Llorente, L., Hernández-Hernández, C., Calderillo, M. L., Marroquín, V., Recillas-Gispert, C., Romero-Díaz, J., & Sánchez-Guerrero, J. (2016). 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. The Journal of Rheumatology, 43(10), 1852-1857.
Hernández-Molina G, et al. 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. J Rheumatol. 2016;43(10):1852-1857. PubMed PMID: 27481899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hernández-Molina,Gabriela, AU - Nuñez-Alvarez,Carlos, AU - Avila-Casado,Carmen, AU - Llorente,Luis, AU - Hernández-Hernández,Carlos, AU - Calderillo,María Luisa, AU - Marroquín,Verónica, AU - Recillas-Gispert,Claudia, AU - Romero-Díaz,Juanita, AU - Sánchez-Guerrero,Jorge, Y1 - 2016/08/01/ PY - 2016/06/20/accepted PY - 2016/8/3/pubmed PY - 2017/11/29/medline PY - 2016/8/3/entrez KW - ANTI-α-FODRIN ANTIBODIES KW - PRIMARY SJÖGREN SYNDROME SP - 1852 EP - 1857 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 43 IS - 10 N2 - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/27481899/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_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=27481899 DB - PRIME DP - Unbound Medicine ER -