Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Biologic therapy in refractory neurobehçet's disease: a multicentre study of 41 patients and literature review.

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.

Efficacy and safety of certolizumab pegol in pregnant women with uveitis. Recommendations on the management with immunosuppressive and biologic therapies in uveitis during pregnancy.

OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.

Current and emerging diagnosis tools and therapeutics for giant cell arteritis.

INTRODUCTION: Giant cell arteritis (GCA) is the most common large-vessel vasculitis in individuals older than 50 years from Western countries. The goal of the treatment is to achieve improvement of symptoms and clinical remission as well as decrease the risk of severe vascular complications. Areas covered: The review summarizes the main epidemiological and clinical features of GCA and discusses in depth both the classic and the new therapies used in the management of GCA. Expert commentary: Prednisone/prednisolone of 40-60 mg/day is the mainstay in GCA therapy. It yields improvement of clinical features and reduces the risk of permanent visual loss in patients with GCA. Other drugs are used in patients who experience relapses (flares of the disease) or side effects related to glucocorticoids. Methotrexate is the most common conventional immunosuppressive drug used as a glucocorticoid sparing agent. Among the new biologic agents, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody, which is effective to improve clinical symptoms, decrease the cumulative prednisone dose, and reduce the frequency of relapses in these patients. Antitumor necrosis factor-α therapy is not useful in GCA. Experience with other biologic agents, such as abatacept or ustekinumab, looks promising but it is still scarce.

Seguridad del sarilumab en pacientes con artritis reumatoide / Safety of sarilumab in patients with rheumatoid arthritis

La artritis reumatoide es una enfermedad inflamatoria, crónica y sistémica, que afecta a las articulaciones periféricas generalmente de forma simétrica. El conocimiento cada vez mayor de las vías patogénicas ha permitido el desarrollo de nuevos fármacos y ampliar las opciones terapéuticas. La interleucina (IL) 6 parece jugar un papel fundamental en la patogenia de la artritis reumatoide. Por ello, el receptor de esta interleucina parece una diana interesante. Inicialmente, el tocilizumab demostró eficacia y seguridad en el tratamiento de la artritis reumatoide. El sarilumab es otro anticuerpo monoclonal dirigido frente al receptor de la IL-6 que, a la vista de los resultados obtenidos en los diferentes ensayos clínicos, muestra una eficacia y perfil de seguridad óptimos en el tratamiento de la artritis reumatoide, totalmente acorde con el bloqueo de la señalización de IL-6, cuya dosis recomendada es de 200 mg cada 2 semanas y, en caso de anormalidades de laboratorio, estas pueden gestionarse reduciendo la dosis a 150 mg cada 2 semanas

Rheumatoid arthritis is a chronic, inflammatory and systemic disease that affects the peripheral joints, usually symmetrically. The increased knowledge of pathogenic pathways has allowed the development of new drugs, thus expanding the therapeutic options. Interleukin-6 seems to play a key role in the pathogenesis of rheumatoid arthritis. Therefore, the interleukin-6 receptor seems to be an interesting target. Initially, tocilizu mab demonstrated efficacy and safety in the treatment of rheumatoid arthritis. Sarilumab is another monoclonal antibody directed against the interleukin-6 receptor which, based on the results obtained in the various clinical trials, shows an optimal efficacy and safety profile in the treatment of rheumatoid arthritis. The safety profile of sarilumab is consistent with the known effect of IL-6 inhibition. The recommended dose is 200 mg every two weeks and, if there are laboratory abnormalities, the dose can be reduced to 150 mg every two weeks

Empatía en estudiantes de la Facultad de Medicina

Antecedentes: La empatía, es un atributo que forma parte importante de la relación médico-paciente. Contribuye de manera positiva al bienestar y la satisfacción de los pacientes. Es una cualidad que se debería de cultivar en estudiantes de medicina. Sin embargo, se ha visto que en las facultades de medicina no se fomenta la empatía y se sugiere que al revés, la carrera juega un papel en su disminución. La empatía, como atributo cognitivo es flexible a la intervención educativa. Por lo tanto, los esfuerzos para promoverla e incorporarla al currículo pueden ayudar a preservarla. Objetivo: Determinar si existe diferencia en puntaje promedio de Empatía estudiantes de la Facultad de Medicina de la Universidad Francisco Marroquín (UFM) de distintos años académicos. Métodos: Se utilizó la Escala de Empatía Médica de Jefferson (EEMJ,) diseñada específicamente para estudiantes en el área de salud. Se administró la prueba a 203 alumnos de primero, tercero, cuarto y séptimo año de la Facultad de Medicina de la UFM. Resultados: Existe diferencia significativa en el puntaje promedio de Empatía entre los distintos años académicos (Fb=13.35 p< 0.001,). Existe un aumento significativo de primero a tercer año, y luego una disminución progresiva en el puntaje promedio de Empatía de tercero a cuarto y de cuarto a séptimo año. No existe diferencia significativa entre primero y séptimo año. Conclusión: Existen diferencias significativas en el puntaje promedio de Empatía entre los distintos años académicos. Para concluir efectivamente que existe una disminución, se deben realizar estudios prospectivos utilizando a las muestras presentes como cohortes y evaluar los cambios en el transcurso de la educación médica. Palabras Clave: educación médica, empatía, estudiantes de medicina, atención plena, relación médico paciente

Background: Empathy is an important attribute, essential in the physician-patient relationship. It positively contributes to the overall well-being and satisfaction of patients. Therefore, it is a quality that should be cultivated in medical students. However, it is reported that instead of enhancing empathy, medical school plays a part in its decline. Empathy, as a cognitive attribute is flexible to educational intervention. Therefore, efforts made towards promoting and incorporating it into a curriculum could help preserve it. Objectives: Determine if there is a difference in the mean score of Empathy in students of Universidad Francisco Marroquín Medical School. Methods: We used the Jefferson Scale of Physician Empathy (JSPE) in its student version, designed specifically for students in healthcare professions. It was administered to a total of 203 students from first, third, fourth and seventh year of UFM Medical School. Results: There is a significant difference in the mean score of empathy between different academic years (Fb=13.35 p< 0.001.) There is a significant increase in the mean score from first to third year, and then a progressive decline from third to fourth, and fourth to seventh year of UFM Medical School. Conclusion: There are significant differences in the mean score of empathy between academic years. To effectively conclude on the decline, prospective studies must be conducted using this sample as a cohort and evaluating the changes through their progress in medical school. Key words: medical education, empathy, medical students, mindfulness, doctor-patient relationship

Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-α therapy.

Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity.

Biologic therapy in ANCA-negative vasculitis.

Standard therapeutic schemes for vasculitis are usually associated with numerous side effects and uneven clinical response. However, recent advances in understanding of the pathogenesis of these systemic diseases have resulted in the development of a group of biologic agents potentially useful in patients with vasculitis. Thus, anti-tumor necrosis factor-α drugs may be effective in patients with refractory Kawasaki disease but have failed to do so in giant cell arteritis, and their role in Takayasu arteritis is yet unclear. Preliminary reports on the use of the anti-IL6-receptor antibody, tocilizumab, in large-vessel vasculitis have been encouraging. Interferon alpha has showed positive results in hepatitis B virus-associated polyarteritis nodosa, and hepatitis C virus-induced cryoglobulinemia. Early experience with rituximab in several types of vasculitis has been quite promising, but must be confirmed in ongoing randomized clinical trials. The development of new biologic targeted therapies will probably open a hopeful future for patients with vasculitis.