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, Characteristics and Survival of Anti-U1 RNP Antibody-Positive Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

B. M. Lynch, , p.3

B. E. Schreiber, , p.3

C. P. Denton, , vol.3

. Objective, This study aimed to investigate the clinical and hemodynamic characteristics and survival of anti-U1

, We compared clinical and hemodynamic characteristics to anti-U1 RNP antibody status. We then assessed whether anti-U1 RNP antibodies could be a prognostic factor in CTD-associated PAH with a focus on SScassociated PAH. Results. We studied a total of 342 patients with CTD-associated PAH, of whom 36 (11%) were anti-U1 RNP antibody positive. Anti-U1 RNP-positive patients were younger and less functionally impaired than were anti-U1 RNP-negative patients in CTD-and SScassociated PAH. Hemodynamic parameters were similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients. In CTD-associated PAH, anti-U1 RNP , sex, functional parameters, lung involvement, and hemodynamic parameters, Results were similar in SSc-associated PAH, although the association between anti-U1 RNP positivity and survival did not reach significance in univariable

, Conclusion. Anti-U1 RNP positivity was associated with distinct clinical characteristics and survival in CTD-and SSc-associated PAH. While hemodynamic parameters were similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients, our results suggest that anti-U1 RNP positivity could be a factor protecting against mortality in CTD-and SSc-associated PAH

. Dr, Sobanski's work was supported by a fellowship funded by the Association des Scl erodermiques de France, the Soci et e Nationale Française de M edecine Interne, Groupe Pasteur Mutualit e, Institut Servier

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. Mots-clés, Le premier travail a été une classification sans a priori des patients de la cohorte européenne EUSTAR (European Scleroderma Trials and Research Group) par une analyse en cluster sur 24 variables sélectionnées (atteintes cliniques, auto-anticorps). Deux puis 6 groupes de patients homogènes ont été obtenus, dont la survie était significativement différente. Ce travail a suggéré qu'il existait des groupes homogènes de patients au-delà de la dichotomie historique forme cutanée diffuse vs. limitée. La présence d'atteintes viscérales et le statut des auto-anticorps apparaissent comme des éléments importants dans la constitution des groupes. Le deuxième travail s'est intéressé au dosage des chaines légères libres sériques (serum free light chain : SFLC) dans la ScS. Le taux de SFLC est plus élevé chez les patients ScS que chez les contrôles et est associé à des paramètres de gravité de la maladie tels que le score de Rodnan, les scores d'activité, les pressions pulmonaires et la DLCO. Cette étude apporte des arguments supplémentaires pour évoquer la participation active des lymphocytes B à la physiopathologie de la ScS. Nous avons ensuite réalisé une estimation de la prévalence des anticorps anti-ARN polymérase de type III dans notre cohorte de patients avec ScS avant d'inclure ces données dans une revue systématique avec méta-analyse, sclérodermie systémique-hétérogénéité-auto-anticorps Résumé : La sclérodermie systémique (ScS) est une connectivite associant atteinte vasculaire, auto-immunité et fibrose. Cette pathologie est associée à une morbi-mortalité importante, et les ressources thérapeutiques sont limitées. La physiopathologie de la ScS n'est que partiellement connue, mais il apparait que les liens entre le système immunitaire et la fibrose sont étroits

, A partir d'une cohorte de patients provenant du centre de référence de l'HTAP du Royaume-Uni, les anticorps anti-U1RNP ont été analysés en tant que marqueur pronostique. Ces anticorps sont associés de façon significative à une meilleure survie des patients avec connectivite et HTAP. Dans la ScS, on observe une tendance vers une meilleure survie également chez les patients porteurs de ces anticorps. Les auto-anticorps constituent donc des biomarqueurs diagnostiques et pronostiques puissants dans la ScS. Ils permettent de mieux cerner l'hétérogénéité de cette pathologie, et devraient probablement être intégrés dans les futures classifications. Leur rôle pathogénique reste encore à démontrer. Les perspectives de notre travail sont d'identifier de nouveaux auto-anticorps, Le dernier travail a été dédié à l'hypertension artérielle pulmonaire (HTAP) des connectivites, en particulier de la ScS