Explore the vast range of titles available.

Background:RA-associated interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) share the MUC5B rs35705950 genetic risk factor and a predilection for the usual interstitial pneumonia (UIP) pattern. The role of telomere-related genes (TRGs) in the RA-ILD genetic background is unclear. Previous work found an excess of TRG rare exonic variants in RA-ILD compared to healthy controls. However, lack of RA controls without ILD precluded an investigation of whether the enrichment for rare variants in TRGs was associated with the RA or ILD pattern.Objectives:To investigate the contribution of TRG rare variants to ILD vs. no ILD in patients with RA, and to IPF vs. healthy controls.Methods:For the RA analyses, this genetic case-control association study consisted of a derivation (France) and a replication (US) sample that included cases with RA-ILD and controls with RA without ILD (RA-noILD). For the IPF analyses, cases with IPF were compared to healthy controls without IPF. Whole exome or genome sequencing was performed in all participants. ILD status and pattern (UIP or non-UIP) was determined by review of clinically-indicated high-resolution computed tomography (HRCT) chest imaging. Exonic variants from 14 candidate TRGs previously associated with IPF or linked to familial pulmonary fibrosis (TERT, TERC, PARN, RTEL1, CTC1, TINF2, ACD, POT1, NAF1, ZCCHC8, NHP2, NOP10, WRAP53, and DKC1) were identified and annotated for their frequency by gnomAD database and their functional impact using predictive tools (SIFT, POLYPHEN-2, and CADD score). Telomere length (TL) was measured in RA cases and controls from the derivation sample, in IPF cases and in non-IPF healthy controls. TRG rare variants enrichment in cases and controls was compared using the classical burden test adjusted for sex, age at RA, RA duration, MUC5B rs35705950 genotype and principal component of ancestry. Derivation and replication results were combined and meta-analyzed. We performed sub-group analyses restricted to cases with TL < 10th percentile.Results:In the RA analyses, the derivation sample included 157 RA-ILD cases and 231 RA-noILD controls, and the replication sample included 85 RA-ILD cases and 305 RA-noILD controls; Table 1. In the derivation sample, we identified 19 distinct rare TRG variants carried by 13/157 RA-ILD cases and 8/231 RA-noILD controls (8.3% vs. 3.5%, OR 2.83, 95% CI 0.96-8.58; p=0.06); Table 2. In the replication sample, an enrichment of TRG rare variants was also observed in RA-ILD cases (9/85 [10.6%] compared to 18/305 [5.9%] in RA-noILD controls, Burden test p=0.20), reaching statistical significance in the meta-analysis analysis (OR 2.12, 95% CI 1.07-4.21, p=0.03). When restricting the analyses to RA-UIP cases, we found a greater enrichment of TRG rare variants in both derivation and replication samples (10.5% and 13.8%, respectively) leading to a significant association with RA-UIP (OR 3.17, 95% CI 1.37-7.32, p=0.007), whereas no association was detected with non-UIP RA-ILD (p=0.33).Similar to RA-ILD and RA-UIP, the analysis of 1277 IPF cases and 1874 non-IPF healthy controls, found a significant excess of rare variants in TRG comparing patients with IPF to healthy controls: 2.0% vs. 1.5%, OR 2.31, 95% CI 1.24-4.37, p=0.013. No interaction between TRG rare variants and smoking status nor MUC5B rs35705950 was detected.When restricting to patients with RA-ILD having a TL<10th percentile, we observed a significant enrichment of TRG rare variants with an increased risk: 10.0% vs. 3.5%, OR 5.93, 95% CI 1.28-26.30, p=0.04. Similar to that observed in RA-ILD, when restricting the analysis to the IPF cases having a TL<10th percentile, a significant excess of TRG rare variants was detected (5.5% vs. 1.5%, OR 6.09 95% CI 2.58-13.50, p=0.0002).Conclusion:In aggregate, our findings provide proof of a contribution of TRGs to ILD risk in RA. Like MUC5B rs35705950, the excess of TRG rare variants support the paradigm of a shared genetic background between RA-ILD and IPF. Similar to IPF, our results indicates that the short TL observed in RA-ILD can be partially attributed to TRG rare variants.REFERENCES:NIL.REFERENCES: NIL. Acknowledgements:Société Française de Rhumatologie.Disclosure of Interests:None declared.

Background:Anti-Ku are rare antibodies (Ab) directed against heterodimeric DNA-binding proteins and detected in some auto-immune diseases (AIDs). In a first study of 42 anti-Ku positive patients, 2 distinct patterns have been yielded thanks to hierarchical clustering. The 1st group corresponded to patients with elevated creatine kinase (CK) levels and an increased risk of interstitial lung disease (ILD); the 2nd one included patients carrying anti-dsDNA antibodies with a high risk of glomerulonephritis [1]. Conclusions drawn may be dampened by the limited number of patients and this subgroup of patients remains partially characterized. To explore the role of anti-Ku positivity in patients with AIDs, a larger cohort with longitudinal assessment of the prognosis is therefore valuable to pursue the phenotypic description, to personalize care management, to monitor and prevent long term complications.Objectives:Using cluster analysis, we aimed to determine distinct patterns of anti-Ku-positivity in AID patients and their respective prognosis.Methods:An observational, multicentric and retrospective study was conducted in 10 University Hospitals in France between January 2010 and March 2022. Inclusion criteria were the positivity of anti-Ku Ab and a suspected AID. We first used an unsupervised multiple correspondence analysis including 19 clinical and biological variables, and then hierarchical clustering to build homogenous clusters of patients. The development of organ involvement throughout the follow-up was also studied. And thereafter, we compared the risk of disease progression, defined as a composite of new organ involvement or by the need for new immunosuppressant, according to each retrieved cluster. This risk was assessed by Cox proportional hazard regression models which estimated hazard ratios (HR) and their 95% confidence intervals (95% CI).Results:A total of 154 patients with anti-Ku Ab were included. At baseline, main diagnoses were inflammatory myopathies (IM, n=51/154, 33%), systemic lupus erythematosus (SLE, n=46/154, 30%), Sjögren’s disease (SjD, n=30, 19%), systemic sclerosis (SSc, n=27/154, 18%), and rheumatoid arthritis (RA, n=12/154, 7.8%). Hierarchical clustering analyses based on 19 selected variables, which did not include disease classification, identified 3 distinct clusters:i)Cluster 1 (n=42/154, 27%) included a majority of patients with IM (n=35/42, 83%) and/or SSc (n=17/42, 40%). All patients had muscle involvement and 7 had myocarditis.ii)Cluster 2 (n=69/154, 45%) included the lowest proportion of women (68%), a majority of patients displayed ILD (n=31/42, 74%), a quarter of the latter fulfilled SjD criteria.iii)Cluster 3 (n=43/154) included younger patients (median age 25 years, vs 52 in cluster 1 and 55 in cluster 2), and the highest proportion of African (58%) and Asian (16%). Patients mainly displayed SLE features and 79% of them fulfilled SLE criteria.These clusters have distinct outcomes (p=0.0014, Figure 1): the 1st cluster mainly developed lung involvement (Figure 2) and displayed a higher risk of disease progression (Figure 1), the 2nd subgroup was prone to myositis development (Figure 1 and 2, HR 0.53, 95% CI 0.33-0.84), and the 3rd subgroup displayed various clinical manifestations (Figure 2), and had the lowest risk of a new immunosuppressant prescription over time (Figure 1, HR 0.42, 95% CI 0.25-0.69). The proportion of patients with heart involvement almost doubled over time in all clusters (Figure 2).Conclusion:Our study delineates 3 phenotypes of patients with anti-Ku Abs: 1/with muscle involvement, 2/with ILD and 3/with SLE features. These clusters had different prognosis and calls for an adapted monitoring and care management of each subgroup of patients.REFERENCES:[1] Spielmann, L. et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Ann Rheum Dis 78, 1101-1106 (2019).Figure 1.Kaplan-Meier curves estimating the risk of new organ involvement and/or new immunosuppressant prescription according to the clusters (N=154).Figure 2.Spider plots illustrating the development of organ involvement over time in each cluster.Acknowledgements:NIL.Disclosure of Interests:Marie Robert: None declared, Yann Nguyen: None declared, Yves Allenbach: None declared, Karim Sacre Novartis, Benjamin Terrier: None declared, Raphael Borie Boehringer Ingelheim, Sanofi and Ferrer, Yurdagul Uzunhan: None declared, Zahir Amoura: None declared, Céline Comparon: None declared, Philippe Dieudé: None declared, Véronique Le Guern: None declared, Capucine Morélot-Panzini: None declared, Marc Humbert: None declared, Olivier Sitbon: None declared, Cécile Goujard: None declared, Brigitte Bader-Meunier: None declared, Bruno Fautrel: None declared, Pascale Chrétien: None declared, Pascale Roland-Nicaise: None declared, Claire Goulvestre: None declared, Jean-Luc Charuel: None declared, Olivier Benveniste: None declared, Luc Mouthon: None declared, Victoire De Lastours: None declared, Perrine Dusser: None declared, Mohamad Zaidan: None declared, Elisabeth Aslangul: None declared, Marie Saillour: None declared, Glory Dingulu: None declared, François Chasset: None declared, Gaetane Nocturne Gaëtane Nocturne received honoraria from Boehringer, Novartis, and travel fees from Amgen, Abbvie., Xavier Mariette Xavier Mariette received consulting fees from Astra Zeneca, Bristol Myer Squib, Galapagos, GSK, Novartis and Pfizer., Samuel Bitoun: None declared, Raphaèle Seror Raphaèle Seror received consulting fees from GSK, Bristol Myer Squib, Boerhinger and Janssen; honoraria from GSK, Bristol Myer Squib, Boehringer, Amgen, Pfizer and Roche; travel fees from Amgen and GSK.

Background and aim: Somatostatin analogues may have antifibrotic properties in the lung. The aim of this study was to evaluate the expression of the five somatostatin receptors sst1 to sst5 in normal and fibrotic mouse lung and the action of SOM230 (pasireotide), a new somatostatin analogue with a long half-life, in bleomycin induced lung fibrosis and in human lung fibroblasts in vitro. Methods: After intratracheal injection of bleomycin, C57Bl6 male mice received one daily subcutaneous injection of SOM230 or saline. The lungs were evaluated on days 3, 7 and 14 after administration of bleomycin. Results: We found that all somatostatin receptors were expressed in the normal mouse lung. The sst2 receptor mRNA expression was increased after bleomycin. SOM230 improved mice survival (69% vs 44%; p = 0.024), reduced lung collagen content at day 14 and decreased lung collagen-1 mRNA at day 7. SOM230 reduced bronchoalveolar lavage inflammatory cell influx at day 3, decreased lung connective tissue growth factor mRNA and transforming growth factor (TGF) β mRNA and increased lung hepatocyte growth factor and keratinocyte growth factor mRNA. The sst2 receptor was strongly expressed in the human lung (normal or fibrotic), particularly by fibroblasts. In vitro, SOM230 reduced BrdU incorporation by control human lung fibroblasts cultured under basal conditions or with TGFβ, and reduced alpha-1 collagen-1 mRNA expression in TGFβ stimulated fibroblasts. Conclusion: We conclude that SOM230 attenuates bleomycin induced pulmonary fibrosis in mice and human lung fibroblasts activation. This study points to a potential new approach for treating pulmonary fibrotic disorders.

BackgroundRheumatoid arthritis–associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) share phenotypic similarities. The gain-of-function MUC5B promoter variant rs35705950 is the strongest risk factor for development of IPFObjectivesWe hypothesised that rs35705950 would also contribute to the risk of ILD in RA patients.MethodsUsing a French discovery population and multi-ethnic validation populations from 6 different countries, we tested the association of the MUC5B promoter variant in RA-ILD (n=620), RA without ILD (n=614), and unaffected controls (n=5448).ResultsThe discovery population revealed an association of the MUC5B promoter variant with RA-ILD when compared to unaffected controls (ORadj=3.8 95% CI: 2.8 to 5.2; p=9.7x10–17) (figure 1A). Similar to the discovery cohort, the MUC5B promoter variant was significantly over-represented among the cases of RA-ILD in the multi-ethnic study cohorts when compared to unaffected controls (OR adj=5.5 95% CI: 4.2 to 7.2; p=4.7x10–35) (figure 1A), and when the discovery population and the multi-ethnic cohorts were combined (OR combined=4.7 95% CI: 3.9 to 5.8; p=1.3x10–49) (figure 1A). Additionally, the MUC5B promoter variant was found to increase the risk of ILD among patients with RA (OR combined=3.1 95% CI: 1.8 to 5.4; p=7.4x10–5), however, no statistical association with the MUC5B promoter variant was observed for RA without ILD (figure 1B). The association of the MUC5B promoter variant with RA-ILD increased significantly when restricted to the usual interstitial pneumonia (UIP) by high-resolution computed tomography (OR combined=6.1 95% CI: 2.9 to 13.1; p=2.5x10–6) (figure 1C). Immunohistochemical and in-situ hybridization analysis of RA-ILD lung tissue demonstrated expression of MUC5B by type 2 alveolar epithelial cells undergoing endoplasmic reticulum stress.ConclusionsOur findings demonstrate that MUC5B promoter variant rs35705950 is a risk factor for RA-ILD specifically associated with radiologic evidence of UIP.Disclosure of InterestNone declared

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease, the most severe manifestation being interstitial lung disease (ILD). Therapeutic options are undefined and ILD is one of the leading causes of mortality for RA patients. A better characterization of RA-ILD–associated factors may improve the risk stratification of RA patients.ObjectivesTo identify variables associated with ILD occurrence in RA.MethodsRA-ILD patients (RA-ILD+) in a French multicentric cohort were compared to monocentric RA cases without ILD (RA-ILD-). All patients fulfilled 2010 ACR/EULAR criteria for RA and had a HRCT chest scan for suspected ILD or during a pre-biologic assessment. ILD was defined by HRCT results. Because ILD occurrence increases with RA duration, RA-ILD+ and RA-ILD- patients were matched by disease duration (1:1). Demographic data, clinical features of RA and treatment modalities before the ILD diagnosis were collected. Results significant on univariate analysis (P<0.15) were selected for multivariate analysis to identify variables independently associated with RA-ILD. Duration of methotrexate (MTX) and anti-TNF agent use was adjusted to mean MTX or anti-TNF duration before ILD diagnosis.ResultsAmong 253 consecutive RA patients, 81 were male (32.02%), 112 (48.07%) were smokers, mean age at RA onset was 48.11 ± 16.33 years, and mean RA duration 11.69 ± 10.10 years; 199 patients (85.78%) were ACPA-positive and 171 (71.85%) had erosive status; 134 (60.63%) received MTX and 63 (28.25%) a TNF inhibitor. Among the 253 patients, 138 (54.55%) had ILD. Among the RA-ILD+ patients, 72 (74.23%) had UIP and 25 (25.77%) NSIP. On univariate analysis, ILD was associated with older age at RA onset (52.69 ± 15.00 vs 42.86 ± 16.26 years, P=0.0001), male sex (40.68% vs 21.74%, P=0.001), ACPA rate ≥60 N (20.63% vs 6.41%, P=0.012), less use of anti-TNF agents and MTX (14.55% vs 41.59%, P=0.001, and 50.94% vs 69.57, P=0.005, respectively) and lower MTX dosage (15.26 ± 4.44 vs 16.83 ± 4.31 mg/week, P=0.046). There was no difference for erosive status. On multivariate analysis, ILD was independently associated with older age at RA onset (P<0.0001), male sex (P=0.0006), less use of MTX (P=0.015) with lower dosage (P=0.005) and less use of anti-TNF agents (P=0.004).ConclusionsAs previously reported, ILD was independently associated with male sex as well as older age at RA onset and, of interest, less use of MTX and anti-TNF biologics before ILD diagnosis, even though patients did not differ in erosive status. Larger prospective studies are required to further elucidate the role of DMARDs and anti-TNF biologics in ILD occurrence and progression in RA patients.Disclosure of InterestNone declared

BackgroundSarcoidosis is a multi-systemic granulomatous disease of unknown cause in which neurological involvement is rare. Corticosteroids remain first line treatment even though immunosuppressive therapy is increasingly prescribed as steroid-sparing agent.ObjectivesTo compare efficiency and safety of methotrexate versus mycophenolate mofetil use to treat neurological involvement of sarcoidosis.MethodsA multicentric retrospective study was performed between 2010 and 2014. Inclusion criteria were: Histologically proven sarcoidosis after exclusion of differential diagnosis, central or peripheral neurologic involvement and prescription of mycophenolate mofetil (MMF) or methotrexate (MTX) for at least one month. Steroid tapering was achieved by local physician habits. The main outcome was the time to relapse. Relapse was defined as the necessity to increase steroids by at least 20 mg per day. Secondary outcomes were safety and switch to second line immunosuppressive therapy.ResultsForty-six patients were included, 14 in the MMF group and 32 in the MTX group. There were 29 males and 17 women. Median age at diagnosis was 38.5 years old range (11-76). Topography of neurological involvements was the brain (27 patients), the cranial nerves (21 patients), the meninges (18 patients), the spinal cord (9 patients), the radiculae (4 patients), the peripheral nerves (4 patients) and the muscle (3 patients).Median follow-up was 84 months. Seventy nine percent of patients relapsed in the MMF group versus 46% in the MTX group. The time to relapse was 11 months in the MMF group vs 28 months in the MTX group. In the survival analysis time to relapse in the MMF group was significantly lower than in the MTX group (p=0.0491). Among relapsing patients 7 (70%) in the MMF group and 13 (87%) in the MTX group required second in immunosuppressive therapy. There was less minor infectious side effects in MMF group 0% than in the MTX 19% group p=0.02.ConclusionsMethotrexate therapy seems to be more efficient in preventing relapse in neurosarcoidosis than mycophenolate mofetil. Safety was good in both groups but with less minor infections in the MMF group. Theses results need to be confirmed in a randomized controlled trial.Disclosure of InterestNone declared

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7x10(-17)). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7x10(-35)) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3x10(-49)). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4x10(-5)), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5x10(-6)). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Societe Francaise de Rhumatologie and others.).

COVID19 due to SARS-CoV-2 infection implies an important anti-viral immune response leading to a major inflammatory syndrome with increased pro-inflammatory cytokine levels (i.e. the cytokine storm paradigm). The impact of a preexisting interstitial lung disease (ILD) on the morbi-mortality of COVID-19 is unclear. An increased mortality rate has been identified in studies that included a limited number of patients with ILD from various etiologies. To date, no studies have investigated the severity of COVID-19 in patients with preexisting ILD in a large population of rheumatic and musculoskeletal diseases (RMD-ILD). Since March 18th, 2020, the French RMD COVID19 dataset (NCT04353609) includes patients with an RMD and SARS-Cov-2 infection. To assess the impact of a preexisting ILD on COVID-19 morbi-mortality within the French RMD COVID-19 dataset. Patients from the French RMD COVID-19 dataset were included in the analysis. COVID-19 diagnosis was established by a positive SARS-CoV-2 PCR test and/or typical symptoms or chest CT scans pattern during the period of the pandemic. Baseline phenotypic characteristics of the RMD including pre-existing ILD prior to the SARS-CoV-2 infection were collected. COVID-19 evolution was characterized as benign (ambulatory care), moderate (hospitalization outside intensive care unit [ICU]) and severe (hospitalization in ICU). Association between the ILD status and the severity and mortality rate of COVID-19 was assessed using multivariable logistic regression adjusted on sex, age, body mass index and diabetes. By June 26, 2020, 897 patients were included. Pre-existing ILD was reported in 27 patients (3%): 11 patients with systemic sclerosis, 8 with rheumatoid arthritis, 2 with auto-immune myositis, 2 with mixed connective tissue disease and 4 with other RMD. Among these 27 patients (11 male, mean age 63.1 ± 16.4 y/o, 56.5% having a usual interstitial pneumonia HRCT pattern), 22 had severe infection. Death related to COVID-19, was observed in 58 patients with RMD without ILD (7.1%) and in 10 patients with RMD-ILD (37%). Having a preexisting ILD was found to be independently associated with an increased risk of severe COVID-19 (adjusted OR=7.6 [2.9 – 20.2], P<0.001) and an increased mortality rate (adjusted OR=12.3 [3.8 – 39.2], P<0.001). In RMD patients with SARS-CoV-2 infection, preexisting ILD was associated with an increased risk to severe COVID-19 and related mortality. Our findings suggest that RMD-ILD patients should be prioritized for COVID-19 vaccination according to the high morbi-mortality rate during SARS-CoV-2 infection. Pierre-Antoine Juge Consultant of: BMS, Eric Hachulla Consultant of: Actelion, Bayer, GSK and Pfizer, Grant/research support from: Actelion, Bayer, GSK and Pfizer, Christophe Richez: None declared, Elodie Drumez: None declared, Alain Duhamel: None declared, Raphael Borie: None declared, Philippe Dieudé: None declared

Background. Bedaquiline is a new antibiotic that was approved for the treatment of multidrug-resistant (MDR) tuberculosis. We aimed to evaluate the short-term microbiological efficacy and the tolerability profile of bedaquiline. Methods. We performed a retrospective cohort study among patients with MDR tuberculosis receiving bedaquiline for compassionate use between January 2010 and July 2013 and evaluated at 6 months of bedaquiline treatment. Results. A total of 35 patients with MDR tuberculosis were included in the study. Nineteen (54%) had extensively drug-resistant (XDR) tuberculosis, and 14 (40%) had isolates resistant to fluoroquinolones (Fqs) or second-line injectables. Bedaquiline was associated with a median of 4 (range, 2–5) other drugs, including linezolid in 33 (94%) cases. At 6 months of bedaquiline treatment, culture conversion was achieved in 28 of 29 (97%) cases with culture-positive pulmonary tuberculosis at bedaquiline initiation. Median time to culture conversion was 85 days (range, 8–235 days). Variables independently associated with culture conversion were treatment with a Fq (P = .01), absence of lung cavities (P < .001), and absence of hepatitis C virus infection (P = .001). A total of 7 patients (20%) experienced a ≥60-ms increase in QT interval, leading to bedaquiline discontinuation in 2 (6%) cases. Severe liver enzyme elevation occurred in 2 patients (6%). During the study period, 1 death (3%) occurred and was reported as unrelated to tuberculosis or antituberculosis treatment. Conclusions. The use of bedaquiline combined with other active drugs has the potential to achieve high culture conversion rates in complicated MDR and XDR tuberculosis cases, with a reassuring safety profile at 6 months of treatment.

Inorganic phosphorus (Pi) fertilizers are expected to become scarce in the near future; so, breeding for improved Pi acquisition-related root traits would decrease the need for fertilizer application. This work aimed to decipher the physiological and molecular mechanisms underlying the differences between two commercial wheat cultivars (Crac and Tukan) with contrasting Pi acquisition efficiencies (PAE). For that, four independent experiments with different growth conditions were conducted. When grown under non-limiting Pi conditions, both cultivars performed similarly. Crac was less affected by Pi starvation than Tukan, presenting higher biomass production, and an enhanced root development, root:shoot ratio, and root efficiency for Pi uptake under this condition. Higher PAE in Crac correlated with enhanced expression of the Pi transporter genes TaPht1;2 and TaPht1;10. Crac also presented a faster and higher modulation of the IPS1-miR399-PHO2 pathway upon Pi starvation. Interestingly, Crac showed increased levels of strigolactones, suggesting a direct relationship between this phytohormone and plant P responses. Based on these findings, we propose that higher PAE of the cultivar Crac is associated with an improved P signalling through a fine-tuning modulation of PHO2 activity, which seems to be regulated by strigolactones. This knowledge will help to develop new strategies for improved plant performance under P stress conditions. © 2020 Elsevier B.V., All rights reserved.