Serum interleukin-17A level is associated with disease activity of adult patients with dermatomyositis and polymyositis.

OBJECTIVES: To assess serum interleukin (IL)-17A levels in patients with dermatomyositis (DM) and polymyositis (PM) and correlate them with the demographic, clinical, laboratory and therapeutic data of these diseases. METHODS: This was a cross-sectional, single-centre study that included defined DM and PM patients who were age-, gender- and ethnicity-matched to healthy individuals. Serum IL-17A analysis, as well as analysis for other cytokines (IL-6, TNFα and IFNγ), was performed by multiplex immunoassay. The disease status parameters were based on the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. RESULTS: Eighty DM, 32 PM patients and 104 healthy individuals were enrolled. Mean age of patients with DM and PM was 46.0 and 47.7, respectively, with a predominance of women and white ethnicity in both groups. Overall, clinical, laboratory, therapeutic, and current disease status were similar among patients with DM and PM. Median serum IL-17A level was higher in patients with PM and DM than the control group (0.73 vs. 0.49 vs. 0.35 pg/mL, respectively; p<0.050) and higher in PM when compared to DM (p<0.001). In DM, serum IL-17A levels were associated with cumulative cutaneous lesions, IMACS parameters, and serum IL-6 and IFNγ levels. In PM, serum IL-17A levels correlated with patients' current age, IMACS parameters and serum TNFα and IFNγ levels. CONCLUSIONS: Serum IL-17A levels are not only increased, but also associated with disease activity in patients with DM and PM. Our data strongly suggest that IL-17A may be a biomarker of disease activity for these systemic autoimmune myopathies.

Muscle biopsies in dermatomyositis and polymyositis: practical relevance of analyzing different levels of histological sections of the same muscular compartment / Biópsias musculares em dermatomiosite e polimiosite: relevância prática da análise de diferentes níveis de cortes histológicos de um mesmo compartimento muscular

ABSTRACT Introdution: It is frequent in medical practice to have findings with normal aspects in histological muscle biopsies from patients with dermatomyositis (DM) or polymyositis (PM). This happens because, for example, the inflammatory infiltrate occurs in foci. Objectives: To evaluate the morphological and histological inflammatory infiltrate in various histological section levels. In addition, to correlate these findings with patients' clinical, laboratory and therapeutic data. Methods: Cross-sectional study in which muscle biopsies from 34 patients were evaluated (DM and PM). From each muscle/patient biopsy block, three levels of histological sections were made (I, II, III) with 400-µm interval between adjacent levels (I × II, and II × III). Semi-quantitative analyses were performed in the following parameters between the adjacent levels: muscle fiber features, conjunctive tissue, vessels, presence of inflammatory cell infiltration. Results: Time spans between muscle biopsy and symptom onset of DM and PM patients were 5.5 and 3.5 months, respectively. All histological parameters analyzed varied between levels and did not correlate with the demographic, clinical, laboratory and therapeutic data before muscle biopsy (p > 0.05). Conclusion: Our results stress the importance of evaluating different levels of histological sections from the same muscle biopsy block, in order to minimize possible false-negative results. In addition, the data reinforce that besides the inflammatory infiltrate, the other histological parameters analyzed also occur in foci, justifying the dissociation between these parameters and clinical patients.

RESUMO Introdução: É frequente na prática médica encontrar achados histológicos com aspectos dentro da normalidade em biópsias musculares de pacientes com dermatomiosite (DM) ou polimiosite (PM). Isso se deve ao fato de, por exemplo, o infiltrado inflamatório ocorrer em focos. Objetivos: Avaliar os aspectos morfológicos e o infiltrado inflamatório em diversos níveis histológicos, bem como correlacionar esses achados com os dados clínicos, laboratoriais e terapêuticos dos pacientes. Métodos: Estudo transversal no qual foram avaliadas biópsias musculares de 34 pacientes (DM e PM). Para cada bloco de biópsia muscular/paciente, foram realizados três níveis de cortes histológicos (I, II e III), com intervalos de 400 µm entre os níveis adjacentes (I × II e II × III). Foram analisados semiquantitativamente os seguintes parâmetros entre os níveis adjacentes: características das fibras musculares, tecido conjuntivo, vasos e presença de infiltrado de células inflamatórias. Resultados: O tempo entre a realização da biópsia muscular e o início de sintomas dos pacientes com DM e PM foi, respectivamente, de 5,5 e 3,5 meses. Todos os parâmetros histológicos analisados variaram entre os níveis e não se correlacionaram com os dados demográficos, clínicos, laboratoriais e terapêuticos pré-biópsia muscular (p > 0,05). Conclusão: Nossos resultados reforçam a importância de avaliar diferentes níveis de cortes histológicos de um mesmo bloco de biópsia muscular com o objetivo de minimizar eventuais resultados falso negativos. Além disso, os dados evidenciam que, além do infiltrado inflamatório, os demais parâmetros histológicos analisados também ocorrem em focos, justificando a dissociação entre esses parâmetros e a clínica dos pacientes.

Exercise in Takayasu Arteritis: Effects on Inflammatory and Angiogenic Factors and Disease-Related Symptoms.

OBJECTIVE: To investigate the effects of acute and chronic exercise in female patients with remissive Takayasu arteritis (TAK). METHODS: This was a 2-part prospective study. In study 1, cytokines and soluble tumor necrosis factor (TNF) receptors were assessed at rest and every 60 minutes during a 3-hour recovery period following an acute exercise session in TAK (n = 11) and heathy control (n = 10) groups. In study 2, a subsample from the TAK group (n = 6) underwent a 12-week exercise training program. Before and after training, the acute session of aerobic exercise was performed and cytokines and soluble TNF receptors were assessed at the same time points described above. Muscle function, strength, aerobic capacity, endothelial function, quality of life, and walking impairment scores were evaluated. RESULTS: In study 1, the acute session of aerobic exercise led to overall similar responses on cytokine kinetics in the TAK and heathy control groups. In study 2, the exercise training program did not exacerbate inflammatory cytokines in TAK patients, while the proinflammatory cytokine TNF was diminished both at rest and following the acute session of aerobic exercise. In addition, the exercise training program increased the pro-angiogenic factors vascular endothelial growth factor (at rest) and platelet-derived growth factor AA (at rest and in response to the acute session of aerobic exercise). The exercise training program improved muscle strength and function, whereas aerobic capacity, quality of life, and endothelial function parameters remained unchanged. CONCLUSION: Exercise could be a well-tolerated, safe, and effective intervention able to induce immunomodulatory and pro-angiogenic effects and to increase strength and function in patients with TAK.