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Vol. 17. Issue 5.
Pages 250-257 (May 2021)
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Vol. 17. Issue 5.
Pages 250-257 (May 2021)
Original article
DOI: 10.1016/j.reumae.2019.10.005
Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications
Patrón de autoanticuerpos contra antígenos nucleares extraíbles (ENA) en pacientes con artritis reumatoide: relevancia e implicaciones clínicas
Yasser Emada,b,
Corresponding author

Corresponding author.
, Yasser Ragabc,d, Nevin Hammame,f, Nashwa El-Shaarawyg, Ossama Ibrahimh, Rania M. Gamalf, Magdy Abd-Elsalami, Reem H.A. Mohammeda, Mona Hawassj, Johannes J. Raskerk
a Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
b Rheumatology Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi Arabia
c Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
d Radiology Department, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi Arabia
e Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
f Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt
g Rheumatology and Rehabilitation Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
h Morecambe Bay University Hospitals Lancaster, Lancashire, UK
i Chest Department, Faculty of Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt
j Nephrology Department, Al-Shorta Hospital, Cairo, Egypt
k Faculty of Behavioural, Management and Social Sciences, Department Psychology, Health and Technology, University of Twente, Enschede, The Netherlands
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Tables (2)
Table 1. Demographic features, disease characteristics, disease activity indices and laboratory findings among the studied group of patients.
Table 2. Correlation between extractable nuclear antigens and clinical features, laboratory findings and disease activity indices in RA patients.
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To study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage.


A total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP.


RF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p=.02), RF titer (p<.001), ANA (p<.001), DAS28-ESR (p=.026), and DAS28-CRP (p=.003). Anti-La antibodies correlated positively with SJC (p=.001), TJC (p=.001), ANA (p<.001), DAS-28 ESR (p=.007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p.001), RF titer (p=.037) and ANA (p.001). Anti-RNP antibodies correlated positively with disease duration (p.001), ACPA titer (p.001) and ANA (p=.014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies.


In RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.

Rheumatoid arthritis (RA)
Rheumatoid factor (RF)
Anticitrullinated peptide/protein antibodies (ACPA)
Antinuclear antibody (ANA)
Extractable nuclear antigens (ENAs) autoantibodies
Anti Jo-1 autoantibody
Anti-synthetase syndrome
Rheumatoid arthritis and anti-synthetase overlap

Estudiar la frecuencia de diferentes autoanticuerpos frente a antígenos nucleares extraíbles (ENA) en pacientes con artritis reumatoide (AR) y relacionar los hallazgos con las manifestaciones clínicas, la actividad de la enfermedad y el daño radiológico.


Se incluyeron un total de 230 pacientes con AR y 75 controles sanos. En todos los pacientes, la evaluación reumatológica, las investigaciones de laboratorio de rutina y el perfil inmune se realizaron tanto en pacientes como en controles, incluidos: RF, ACPA, ANA y anti-ENA (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 y anti-sm). El daño radiológico se puntuó con Sharp/van der Heijde y la actividad de la enfermedad se evaluó mediante DAS28-ESR y DAS28-CRP.


La RF fue positiva en 101 (43.9%), ACPA en 220 (95.7%), ANA en 58 (25.2%), anti Ro en 31 (13.5%), anti-La en 10 (4.3%), anti-Jo1 en 5 (2,2%) y anti-RNP en 2 (0,9%). Anti-Ro/SSA se correlacionó positivamente con los síntomas de sicca (p=.02), el título de RF (p<.001), ANA (p<.001), DAS28-ESR (p=.026) y DAS28-CRP (p=.003). Los anticuerpos anti-La se correlacionaron positivamente con SJC (p=.001), TJC (p=.001), ANA (p<.001), DAS-28 ESR (p=.007). El anti-Jo-1 se correlacionó positivamente con la enfermedad pulmonar intersticial (EPI) (p0,001), título de RF (p=0,037) y ANA (p0,001). Los anticuerpos anti-RNP se correlacionaron positivamente con la duración de la enfermedad (p0,001), el título de ACPA (p0,001) y ANA (p=0,014). En los controles, ANA fue positivo en dos (2.7%), anti-Ro en tres (4%) y ninguno de los controles dio positivo para otros autoanticuerpos.


En pacientes con AR, el ANA positivo es frecuente y se asocia positivamente con autoanticuerpos anti-Ro, anti-La y anti-Jo1. La detección de autoanticuerpos contra otros anti-ENA parece obligatoria en los pacientes con AR, especialmente cuando la ANA es positiva. Los casos de AR con Anti-Jo-1 positivo pueden desarrollar el síndrome de sintetasa e ILD.

Palabras clave:
Artritis reumatoide (AR)
Factor reumatoide (RF)
Anticuerpos péptido/proteína anticitrulinados (ACPA)
Anticuerpo antinuclear (ANA)
Antígenos nucleares extraíbles (ENA) autoanticuerpos
Anti Jo-1 autoanticuerpo
Síndrome anti-sintetasa
Artritis reumatoide y superposición de sintetasa


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