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Vol. 162. Issue 8.
Pages 370-377 (April 2024)
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Vol. 162. Issue 8.
Pages 370-377 (April 2024)
Original article
Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis
Valor pronóstico de los autoanticuerpos anti-IFI16 en la hipertensión arterial pulmonar y en la mortalidad en los pacientes con esclerodermia sistémica
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Janire Perurena-Prietoa,b,c, Eduardo L. Callejas-Moragad, María T. Sanz-Martíneza, Roger Colobrana,b,c,e,
Corresponding author
roger.colobran@vallhebron.cat

Corresponding authors.
, Alfredo Guillén-Del-Castillof,1,
Corresponding author
alfredo.guillen@vallhebron.cat

Corresponding authors.
, Carmen P. Simeón-Aznarf,1
a Immunology Division, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
b Translational Immunology Group, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
c Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Spain
d Internal Medicine Department, Hospital Público de Monforte, Lugo, Spain
e Department of Clinical and Molecular Genetics, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
f Systemic Autoimmune Diseases Unit, Internal Medicine Department, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
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Tables (2)
Table 1. Indirect immunofluorescence (IIF) patterns observed in HEp-2 cells from SSc-seronegative patients.
Table 2. Demographic and clinical characteristics of the 124 SSc patients, showing comparisons between anti-IFI16 autoantibodies reactivity in SSc-seronegative and ACA-positive patients.
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Abstract
Objectives

To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA).

Methods

Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed.

Results

Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043).

Conclusion

Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome.

Keywords:
Systemic sclerosis
Interferon gamma inducible protein 16
Autoantibodies
Prognostic factors
Pulmonary arterial hypertension
Mortality
Resumen
Objetivos

Determinar el valor diagnóstico de los autoanticuerpos anti-interferon gamma inducible protein 16 (IFI16) en los pacientes con esclerodermia sistémica (SSc) negativos para todos los autoanticuerpos específicos de SSc (pacientes SSc seronegativos) y evaluar el significado clínico de estos autoanticuerpos, aislados o en combinación con autoanticuerpos anticentrómero (ACA).

Métodos

Se incluyeron 58 pacientes SSc seronegativos y 66 pacientes ACA positivos. Todos los pacientes se testaron para los autoanticuerpos anti-IFI16 mediante un ELISA directo «in-house». Las asociaciones entre parámetros clínicos y los autoanticuerpos anti-IFI16 fueron analizadas.

Resultados

En total, el 17,2% de los pacientes SSc seronegativos y el 39,4% de los pacientes ACA positivos fueron positivos para anti-IFI16. Los autoanticuerpos anti-IFI16 se detectaron solamente en los pacientes con la forma limitada cutánea de SSc (lcSSc). Se encontró una asociación entre la positividad de anti-IFI16 y la hipertensión arterial pulmonar (HAP) aislada (odds ratio [OR]: 5,07; p=0,014), incluso cuando se ajustó el análisis a la presencia o ausencia de ACA (OR: 4,99; p=0,019). Los pacientes anti-IFI16 positivos mostraron una peor supervivencia general que los pacientes negativos (p=0,032). Las ratios de supervivencia acumulada a 10, 20 y 30 años fueron respectivamente del 96,9, 92,5 y 68,7% para los pacientes anti-IFI16 positivos frente al 98,8, 97,0 y 90,3% para los anti-IFI16 negativos. Los pacientes anti-IFI16 positivos también tenían una supervivencia general menor que los pacientes anti-IFI16 negativos tras ajustar para la presencia o ausencia de ACA mediante análisis multivariado de Cox (hazard ratio [HR]: 3,21; p=0,043).

Conclusión

Los autoanticuerpos anti-IFI16 se asocian con HAP aislada y una peor supervivencia general. Los autoanticuerpos anti-IFI16 se podrían emplear como marcador suplementario de lcSSc en pacientes SSc seronegativos y para identificar pacientes ACA positivos con un peor pronóstico.

Palabras clave:
Esclerodermia sistémica
Interferon gamma inducible protein 16
Autoanticuerpos
Factores pronósticos
Hipertensión arterial pulmonar
Mortalidad

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