Bernard Bonnotte

Objectives: Acute anterior ischaemic optic neuropathy (AION) is a feared ischaemic complication of giant cell arteritis (GCA). However, distinguishing arteritic AION (A-AION) from its non-arteritic counterpart (NA-AION), which accounts for approximately 90% of cases, can be challenging. Rapid initiation of glucocorticoids is essential to prevent irreversible vision loss in GCA but is unnecessary in NA-AION. This study evaluated the use of orbital MRI in differentiating A-AION from NA-AION. Methods: In this prospective single-centre study, patients >50 years who had recent-onset AION were enrolled between June 2021 and October 2024. The final diagnosis of GCA was confirmed after comprehensive assessments and ≥6 months follow-up. Orbital MRIs were independently evaluated by two experienced radiologists blinded to the clinical diagnosis. Results: Of the 18 patients analysed, nine had A-AION (two with bilateral involvement), while nine had NA-AION. MRI demonstrated differences between the groups, notably in contrast enhancement of the ophthalmic artery (72.7% vs 22.2%; p=0.07), perineural fat (90.9% vs 22.2%; p=0.005) and retrobulbar fat (100% vs 11.1%; p<0.001). The most discriminative MRI feature was retrobulbar fat enhancement, achieving 100% (95% CI 72 to 100) sensitivity and 89% (95% CI 52 to 100) specificity. Bilateral orbital enhancement was identified in more than half of the unaffected contralateral eyes in A-AION patients. Conclusion: These results suggest that orbital MRI may help clinicians rapidly differentiate between A-AION and NA-AION to provide the most appropriate treatment.

Background: Mixed connective tissue disease (MCTD) has long been debated as an early nonspecific phase/symptom of differentiated connective tissue diseases (dCTD), similarly to interstitial pneumonia with autoimmune features (IPAF) and very early diagnosis of systemic sclerosis (SSc) (VEDOSS). Objective: We aimed to evaluate the predictive value of IPAF, VEDOSS and dCTD classification criteria variables in MCTD patients. Methods: We conducted an observational study within the French MCTD cohort. IPAF, VEDOSS and current dCTD classification criteria were used to classify patients. Results: Three hundred and twenty-four MCTD patients were included and followed for 8 (3.3–13) years. Among them, 111 (34.3%) progressed into a dCTD, that is, 50 (15.4%) SSc, 40 (12.3%) systemic lupus erythematosus (SLE) and 11 (3.4%) Sjögren’s disease. At diagnosis, 38 (11.7%) patients fulfilled IPAF criteria, among which 15 (39.5%) progressed into a dCTD (vs 75 (26.2%) in patients who did not fulfil IPAF criteria; p=0.09). At diagnosis, 293 (90.4%) patients fulfilled VEDOSS criteria but did not progress significantly more frequently to SSc than MCTD patients without VEDOSS criteria (46 (15.7%) vs 4 (12.9%); p=0.8). At baseline, SSc classification criteria did not predict evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE (p=0.01 and p=0.04, respectively). Conclusion: At MCTD diagnosis, fulfilment of IPAF and/or VEDOSS criteria was not predictive of evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE. This suggests that MCTD patients should be excluded from IPAF and VEDOSS.

Objective: To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse. Methods: Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression. Results: Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse. Conclusion: Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.

Summary: Suppressive myeloid cells play a central role in cancer escape from anti-tumor immunity. Beyond their immunosuppressive function, these cells are capable of exerting multiple other pro-tumoral activities, including the promotion of cancer cell survival, invasion and metastasis. The ability of some myeloid subsets to induce cancer stemness has recently emerged. Here we demonstrated that human immunosuppressive myeloid cells, generated in vitro or isolated from breast cancer patients, promoted the acquisition of mesenchymal-like breast cancer stemness properties. This cancer-stemness-inducing function was restricted to a myeloid subset expressing the glycoprotein CD52. Single cell transcriptomic- and surface proteome-based interactome analysis pointed towards membrane-bound TGF-β1 as a potential factor involved in cancer stemness induction. Functional inhibition of the TGF-β1 pathway blocked the emergence of cancer stem cells induced by suppressive myeloid cells. These results therefore identified the underlying mechanisms of a new tumor-promoting function of immunosuppressive myeloid cells, which may potentially be targeted. Highlights: Immunosuppressive CD33 ^high CD52 ⁺ myeloid cells induce mesenchymal-like cancer stem cells Cancer stemness induction requires membrane bound TGF-β1 Blockade of the TGF-β1 pathway prevents cancer stemness induction

Background and aims Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments. Methods We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction Results We included 1048 patients with available data regarding treatment. Regarding sildenafil analyses, the ATE on diastolic dysfunction at 3 years was −2.83% (95% CI −4.06; −1.60, pConclusions Using causal methods, our study is the first and largest suggesting that sildenafil might have benefits among SSc patients regarding diastolic dysfunction and altered ejection fraction occurrence. However, further studies assessing the effect of vasodilators on heart-related outcome among SSc patients are needed to confirm those exploratory results.

Introduction Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used to identify GCA in cases of apparently isolated PMR. Materials and methods 45 patients with isolated PMR and 29 patients with PMR/GCA overlap were included. Blood samples were collected before starting glucocorticoids for all patients. Serum biomarkers reflecting systemic inflammation (interleukin-6 (IL-6), CXCL9), vascular remodelling (MMP-2, MMP-3, MMP-9) and endothelial function (sCD141, sCD146, ICAM-1, VCAM-1, vWFA2) were measured by Luminex assays. Results Patients with GCA had higher serum levels of sCD141 (p=0.002) and CXCL9 (p=0.002) than isolated PMR. By contrast, serum levels of MMP-3 (p=0.01) and IL-6 (p=0.004) were lower in GCA than isolated PMR. The area under the curve (AUC) was calculated for sCD141, CXCL9, IL-6 and MMP-3. Separately, none of them were >0.7, but combinations revealed higher diagnostic accuracy. The CXCL9/IL-6 ratio was significantly increased in patients with GCA (p=0.0001; cut-off >32.8, AUC 0.76), while the MMP-3/sCD141 ratio was significantly lower in patients with GCA (pConclusion Combined serum biomarkers such as CXCL9/IL-6 and MMP-3/sCD141 could help identify GCA in patients with isolated PMR. It could allow to select patients with PMR in whom complementary examinations are needed.

Purpose The aim of our study was to investigate the long-term effects of splenectomy on the immune response and to compare these effects in two groups of patients splenectomized for different reasons, autoimmune cytopenia or following trauma, and healthy non-splenectomized controls in a single-center cohort study. Methods Among 248 patients splenectomized for ITP or trauma between 1995 and 2015 at Dijon University Hospital, 15 patients randomly selected from the two groups and 10 matched controls (healthy non-splenectomized patients) were analyzed. Results Splenectomized patients in both ITP and trauma groups had a higher circulating cell count and percentage of B lymphocytes than controls, a significant decrease in memory B cells, memory IgM B cells, marginal zone B cells and switched memory B cells. On the other hand, we found no changes in the different T-cell subsets of patients splenectomized for ITP or trauma and controls, with the exception of an increase in circulating CD8⁺ central memory T cells in both splenectomized groups compared to controls. Interestingly, we also found a decrease in the phagocytosis capacity in the splenectomized ITP group, partially corrected by the addition of tuftsin, but no abnormalities in the oxidative functions. Conclusion In summary, we demonstrated long-term immunological consequences of splenectomy which did not differ according to the indication for splenectomy, ITP or trauma and noted a decline in phagocytic capacity.