Soluble Axl is an accurate biomarker of cirrhosis and hepatocellular carcinoma development: results from a large scale multicenter analysis.
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Retamozo Soledad, Acar-Denizli Nihan, Horváth Ildiko Fanny, Ng Wan-Fai, Rasmussen Astrid, Dong Xu, Li Xiaomei, Baldini Chiara, Olsson Peter, Priori Roberta, Seror Raphaèle, Gottenberg Jacques-Eric, Kruize Aike A, Hernandez-Molina Gabriela, Vissink Arjan, Sandhya Pulukool, Armagan Berkan, Quartuccio Luca, Sebastian Agata, Praprotnik Sonja, Bartoloni Elena, Kwok Seung-Ki, Kvarnstrom Marika, Rischmueller Maureen, Soláns-Laqué Roser, Sene Damien, Pasoto Sandra G, Suzuki Yasunori, Isenberg David A, Valim Valéria, Nordmark Gunnel, Nakamura Hideki, Fernandes Moça Trevisani Virginia, Hofauer Benedikt, Sisó-Almirall Antoni, Giacomelli Roberto, Devauchelle-Pensec Valerie, Bombardieri Michele, Atzeni Fabiola, Hammenfors Daniel, Maure Brenda, Carsons Steven E, Gheita Tamer, Sánchez-Berná Isabel, López-Dupla Miguel, Morel Jacques, Inanç Nevsun, Fonseca-Aizpuru Eva, Morcillo César, Vollenweider Cristina, Melchor Sheila, Vázquez Marcos, Díaz-Cuiza Ericka, Consani-Fernández Sandra, de-Miguel-Campo Borja, Szántó Antónia, Bombardieri Stefano, Gattamelata Angelica, Hinrichs Anneline, Sánchez-Guerrero Jorge, Danda Debashish, Kilic Levent, De Vita Salvatore, Wiland Piotr, Gerli Roberto, Park Sung-Hwan, Wahren-Herlenius Marie, Bootsma Hendrika, Mariette Xavier, Ramos-Casals Manuel, Brito-Zerón Pilar, Sjögren Big Data Consortium
Аннотация
METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.
RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).
CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.