Showing papers by "Corinne Miceli-Richard published in 2022"

Characterization of Blood Mucosal Associated Invariant T (MAIT) cells in Axial Spondyloarthritis and of resident MAITs from control axial enthesis.

Abstract: OBJECTIVES The importance of IL-17A in the pathogenesis of Axial Spondyloarthritis (AxSpA) has been demonstrated by the success of IL-17A blockade. However, the nature of the cell populations producing this important pro-inflammatory cytokine remains poorly defined. Accordingly, we characterized major IL-17A-producing blood cell populations in AxSpA, with reference to entheseal biology, with a focus on mucosal associated invariant T-cells, (MAITs) a population known to be capable of producing IL-17. METHODS IL-17A production from 5 sorted peripheral blood cell populations, namely MAITs, γδ T-cells, CD4+T-cells, CD8+T-cells and neutrophils was evaluated pre- and post-stimulation with PMA, the calcium ionophore A23187 and β1,3 glucan. IL-17A transcript and protein expression were determined using nCounter Technology and ultra-sensitive SimoA technology, respectively. MAITs from control human axial entheses (n=5) were further characterized by flow cytometric immunophenotyping, qPCR and IL-17 production assessed following stimulation. RESULTS In blood, on a per cell basis, MAIT cells produced the highest amount of IL-17A compared to CD4+ (p <0.01), CD8+ (p <0.0001) and γδ T-cells (p <0.0001). IL-17A was not produced by neutrophils. Gene expression analysis also showed significantly higher IL17A and IL23R expression in MAIT cells. Stimulation of blood MAIT cells with αCD3/CD28 and IL-7 and/or IL-18 induced strong expression of IL17F. MAITs were present in the normal enthesis and showed elevated AHR, JAK1, STAT4 and TGFB1 transcript expression with inducible IL-17A protein. IL-18 protein expression was evident in spinal enthesis digests. CONCLUSION Both blood MAITs and resident MAITs in axial entheses contribute to IL-17 production and may play important roles in AxSpA pathogenesis.

Characterization of Blood Mucosal‐Associated Invariant T Cells in Patients With Axial Spondyloarthritis and of Resident Mucosal‐Associated Invariant T Cells From the Axial Entheses of Non‐Axial Spondyloarthritis Control Patients

Abstract: The importance of interleukin‐17A (IL‐17A) in the pathogenesis of axial spondyloarthritis (SpA) has been demonstrated by the success of IL‐17A blockade. However, the nature of the cell populations that produce this important proinflammatory cytokine remains poorly defined. We undertook this study to characterize the major IL‐17A–producing blood cell populations in the peripheral blood of patients with axial SpA, with a focus on mucosal‐associated invariant T (MAIT) cells, a population known to be capable of producing IL‐17.

Evaluation of Patients With Rheumatoid Arthritis in Teleconsultation During the First Wave of the COVID-19 Pandemic

Abstract: Objective To describe which variables were collected by rheumatologists to monitor patients with rheumatoid arthritis (RA) during teleconsultation and identify which ones have more impact on clinician intervention. Methods Retrospective monocentric, routine care cross-sectional study including patients with RA seen in teleconsultation between March and September 2020. Available variables assessing disease status were collected in teleconsultation files. Clinician intervention was defined by treatment escalation and/or the need for a rapid face-to-face consultation or day hospitalization. Results One hundred forty-three patients with RA were included (116 females, mean age of 58 [SD 16] yrs, mean disease duration of 14 [SD 11] yrs). The presence or absence of patient self-reported RA flares was mentioned in all medical files, followed by the presence and/or the number of tender joints (76%), the duration of morning stiffness (66%), the number of pain-related nocturnal awakenings (66%) and the C-reactive protein (CRP) value (54%). Teleconsultation led to a clinician intervention in 22/143 patients (15%), representing 51% of patients with self-reported flares (22/43 patients). Therapeutic escalation was necessary in 13 patients and/or face-to-face consultation or day hospitalization were organized for 10 patients. Multivariate analysis identified RA flares (odds ratio [OR] 15.6, 95% CI 3.37-68.28) and CRP values > 10 mg/L (OR 3.32, 95% CI % 1.12-13.27) as the variables independently associated with clinician intervention. Conclusion Our study identified patient-reported RA flares and increased CRP values as 2 red flags in teleconsultation, independently associated with therapeutic modification and/or the need for a rapid face-to-face consultation. These indicators may help clinicians’ decision making in teleconsultation.

Increased antibody response after SARS-CoV-2 mRNA-based vaccination in rituximab-treated patients with previous COVID-19 infection

Abstract: DEAR EDITOR, Rituximab (RTX) is associated with reduced humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-based vaccine [1, 2]. A recent study has shown that a single dose of SARS-CoV-2 mRNA-based vaccine was sufficient to obtain a robust humoral response in immunocompetent individuals with a previous history of coronavirus disease 2019 (COVID-19) [3]. While research has demonstrated that immunodeficient kidney transplant recipients (KTRs) who received mRNAbased vaccines show low immunization rates, KTRs with previous exposure to SARS-CoV-2 exhibited a marked increase in antibody titre, even after a single dose of vaccine [4]. Whether this also applies to RTXtreated patients with a history of COVID-19 is unknown. Our aim was to depict the results of immunization after 1–3 doses of mRNA-based SARS-CoV-2 vaccine in RTX-treated patients with previous symptomatic COVID-19 infection. We conducted an observational prospective usual-care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients were closely followed up by the department, including the use of RT-PCR for SARS-CoV-2 detection in case of any symptoms. All patients received a 1–3-dose regimen of mRNA-based COVID-19 vaccination (BNT162b2 Pfizer/BioNTech or mRNA-1273, Moderna). Serum IgG antibody levels against SARS-CoV-2 spike proteins were measured at the time of the following RTX infusion. The LIAISON R SARS-CoV-2 S1/S2 IgG immunoassay (DiaSorin) was used for the quantitative determination of antibodies to the receptor-binding domain of the viral spike (S) protein. Seropositivity was defined as SARSCoV-2 Spike antibodies measured at >15 arbitrary Units (AU)/ml. The protocol and the informed consent document received Institutional Review Board/Independent Ethics Committee (IRB/IEC) approval before initiation of the study (Comit e de Protection des Personnes Paris Ile de France I, No. CPPIDF-DAP13). All patients agreed to participate in this study and provided written informed consent, which was recorded in the medical source file. All data were expressed as median values with 95% CIs or as number and percentage (%) for continuous and categorical variables, respectively. Statistical analysis was performed using GraphPad Prism (v9.1.2) and Medcalc (v18.9.1). We used the Mann–Whitney U test and the Kruskall–Wallis test for variance on ranks for continuous variables. The v test was used to test for differences in frequency (categorical variables). We included 69 patients (60 females, median age 63 years, 95% CI 56–68 years) on maintenance therapy with RTX, including 13 with previous symptomatic COVID-19, all proven by RT-PCR (10 females, median age 58 years, 95% CI 47–70 years, of whom 3 had severe disease, defined by the need of hospitalization and/ or oxygen requirement) (Supplementary Table S1, available at Rheumatology online). Symptomatic COVID-19 occurred between March 2020 and May 2021. The median interval between the last RTX infusion and COVID-19 was 83 days (95% CI 44–179 days), and the median interval between COVID19 and the next RTX infusion was 131 days (95% CI 114–267 days). The median interval between COVID-19 and the first dose of vaccine was 262 days (95% CI 151–365 days), and the serological response was assessed after a median of 58 days (95% CI 32– 151 days) from the last dose of vaccine (third dose for 3 patients, second dose for 6 patients and first dose for 4 patients) (Fig. 1A). The 56 patients with no history of symptomatic COVID-19 infection all received three doses of vaccine (median time between the RTX infusion and the first dose of vaccine: 145 days, 95% CI 126– 180 days). The serological response was assessed after a median of 59 days (95% CI 50–76 days) from the third dose of vaccination. These patients did not differ from those with a history of symptomatic COVID-19 with respect to age, gender, underlying disease, disease duration, associated CSs or DMARDs, RTX cumulative dose, or CD19 counts (Supplementary Table S1, available at Rheumatology online). The seropositivity rate was significantly higher in RTX-treated patients with previous symptomatic COVID-19 infection (11/13, 85% vs 15/56, 27%, P<0.001). SARS-CoV-2 spike antibodies were also markedly increased in patients with previous symptomatic COVID-19 infection (median 119 AU/ml, 95% CI 16–400 AU/ml vs 3.80 AU/ml, 95% CI 3.80– 4.81 AU/ml P< 0.001) (Fig. 1B). SARS-CoV-2 spike antibody titres did not significantly differ in the 26 seropositive patients according to history of COVID-19 (median 328 AU/ml, 95% CI 66–400 AU/ml vs 178 AU/ml, 95% CI 49–400 AU/ml P1⁄40.44) (Supplementary Fig. S1, available at Rheumatology online). SARS-CoV-2 spike Rheumatology key message

Hip Pain Associated with Acetabular Dysplasia in Patients with Suspected Axial Spondyloarthritis: DESIR Cohort Data

Abstract: To determine whether acetabular dysplasia is associated with hip pain at physical examination among adults with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA).This cross-sectional ancillary study was conducted on the prospective DESIR cohort, which enrolled patients aged 18-50 years who had recent-onset IBP. Two readers used antero-posterior pelvic radiographs to assess the Tönnis angle, acetabular angle (AA), lateral centre-edge angle (LCEA), and femoral head extrusion index (FHEI). Abnormality of one or more of these four variables defined acetabular dysplasia. Hip pain upon physical examination was assessed based on Ritchie's articular index.The overall prevalence of acetabular dysplasia was 22% (139/636). The proportion of females was higher in the group with acetabular dysplasia. Hip pain was found in 21% (29/139) of patients with versus 12% (59/497) without acetabular dysplasia (OR, 1.96; 95% CI, 1.20 to 3.20); the association was significant in males (OR, 3.14; 95% CI, 1.44 to 6.86) but not females (OR, 1.39; 95% CI, 0.74 to 2.62). Results were similar when acetabular dysplasia was defined on the basis of LCEA alone (OR, 2.15; 95% CI, 1.18 to 2.62).Among patients with recent-onset IBP suggesting axSpA, acetabular dysplasia was significantly associated with hip pain in males. Hip pain related to acetabular dysplasia might result in overdiagnosis of hip involvement by axSpA.

Reply to Toussirot et al.

Abstract: IL-17A was higher in axial SpA patients compared with controls. We previously evaluated a series of patients with radiographic axial SpA and found that patients with axial SpA had a higher proportion of IL-17A/interferon-γ–producing MAIT cells and IL-22– producing MAIT cells (2). As reported in an SKG mouse model that develops an SpA-like disease, the synergistic effects of IL-22 and IL-17A are required to promote enthesitis (3). In a mouse model of arthritis, overexpression of IL-23 induced the production of IL-22 by entheseal IL-23R+CD4−CD8−CD3+ T cells, with the involvement of IL-22 in the induction of genes implicated in bone proliferation (4). Although Rosine et al highlighted the presence of MAIT cells in entheseal structures of healthy subjects and reported that these cells expressed the vascular endothelial growth factor gene involved in angiogenesis (VEGFA) at high levels, we currently do not know the specific expression of MAIT cells within the sites of inflammation in axial SpA patients. Moreover, IL-22 production by resident entheseal MAIT cells was not examined by Rosine et al. Finally, MAIT cells are primarily expressed at mucosal surfaces and in the blood, but they also express chemokine receptors and can migrate to specific tissues, such as the gut. With the consideration of the involvement of the gut and joint in axial SpA, attention should also be given to the specific expression of chemokine receptors (e.g., CCR9) associated with α4β1 and α4β7 integrins by MAIT cells. Author disclosures are available at https://onlinelibrary.wiley.com/ action/downloadSupplement?doi=10.1002%2Fart.42278&file=art42278sup-0001-Disclosureform.pdf.

Clinical Connections

Abstract: • MAITs cell could be a candidate cell type linking gut and axial inflammation in SpA. SUMMARY Axial spondyloarthritis (AxSpA) shows strong associations with gut mucosal abnormalities that are frequently subclinical, but even so, such silent inflammation is associated with active axial inflammatory episodes. The normal intestine has numerous resident populations of both adaptive and innate lymphocytes, the latter of which includes mucosal-associated invariant T cells (MAITs). The MAIT population plays important roles in immunity and is regulated strongly by intestinal microbiota and B vitamin complex metabolites. It is suspected that MAITs may also traffic from the intestine to other sites. Rosine et al investigated MAITs in the blood in active AxSpA, and determined whether such cells were actually resident in the normal spinal enthesis tissue, a key target for skeletal pathology.