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ABSTRACT Background: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. Objective: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. Methods: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. Results: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. Conclusions: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

RESUMO Antecedentes: Caracterizada por desmielinização, inflamação e dano axonal, a esclerose múltipla (EM) é uma das doenças mais comuns do sistema nervoso central liderada pelo sistema imunológico. Há uma necessidade urgente e óbvia de biomarcadores para o diagnóstico e acompanhamento da EM. Objetivo: Investigar os níveis séricos de sestrina2 (SESN2), uma proteína que responde ao estresse agudo, em pacientes com EM. Métodos: Foram incluídos 85 participantes, 40 pacientes com diagnóstico prévio de EM recorrente-remitente e 45 controles saudáveis. Os parâmetros do SESN2 sérico foram investigados em amostras de sangue coletadas de cada participante nos grupos de paciente e controle. Resultados: os níveis de SESN2 foram significativamente mais baixos em pacientes com EM do que em controles (z: -3,06; p=0,002). Na análise ROC do SESN2, o nível preditivo para MS foi 2,36 ng/mL [sensibilidade, 72,50%; especificidade, 55,56%; p=0,002; área sob a curva (AUC)=0,693]. Para o valor de corte em ambos os grupos, SESN2 foi um preditor independente para MS [Exp (B)=3,977, intervalo de confiança de 95% (95%CI) 1,507-10,494; p=0,013]. Conclusões: A expressão diminuída de SESN2 pode desempenhar um papel na patogênese da EM, e SESN2 poderia ser usado como um biomarcador para EM e como agente imunoterapêutico para o tratamento de EM.

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BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. OBJECTIVE: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). METHODS: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. RESULTS: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. CONCLUSION: The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.

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BACKGROUND: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. OBJECTIVE: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. METHODS: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. RESULTS: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. CONCLUSIONS: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

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BACKGROUND: Migraine is a multifactorial neurovascular syndrome and closely associated to inflammation. Cystatin C (Cys C) is a neuroendocrine polypeptide which also plays a role in inflammation. Objective: To investigate the levels of Cys C in migraine patients without aura. METHODS: A total of 80 participants were included in the study; 40 patients and 40 healthy controls. Serum Cys C levels were investigated by using enzyme-linked immunosorbent assay (ELISA). Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, IL, USA). RESULTS: Serum Cys C levels were found as 73.88 ng/mL in the patient group and 24.92 ng/mL in the healthy control group, being significantly higher among patients (p=0.000). Serum Cys C levels were significacntly different across age subgroups among patients (p=0.049), but not among controls. However, visual analog scale (VAS) (p=0.707), disease duration time (p=0.725) and body mass index (p=0.136) were not significantly different between the two groups. CONCLUSION: Our findings demonstrate that high serum Cys C levels are independently associated to migraine without aura. To the best of our knowledge, this is the first study to determine the serum levels of Cys C in patients with migraine. Thus, serum Cys C may be a potential biomarker of migraine.

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ABSTRACT Background: Migraine is a multifactorial neurovascular syndrome and closely associated to inflammation. Cystatin C (Cys C) is a neuroendocrine polypeptide which also plays a role in inflammation. Objective: To investigate the levels of Cys C in migraine patients without aura. Methods: A total of 80 participants were included in the study; 40 patients and 40 healthy controls. Serum Cys C levels were investigated by using enzyme-linked immunosorbent assay (ELISA). Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, IL, USA). Results: Serum Cys C levels were found as 73.88 ng/mL in the patient group and 24.92 ng/mL in the healthy control group, being significantly higher among patients (p=0.000). Serum Cys C levels were significacntly different across age subgroups among patients (p=0.049), but not among controls. However, visual analog scale (VAS) (p=0.707), disease duration time (p=0.725) and body mass index (p=0.136) were not significantly different between the two groups. Conclusion: Our findings demonstrate that high serum Cys C levels are independently associated to migraine without aura. To the best of our knowledge, this is the first study to determine the serum levels of Cys C in patients with migraine. Thus, serum Cys C may be a potential biomarker of migraine.

RESUMO Introdução: A enxaqueca é uma síndrome neurovascular multifatorial e está intimamente associada à inflamação. A cistatina C (Cys C) é um polipeptídeo neuroendócrino que também desempenha papel importante na inflamação. Objetivo: Investigar os níveis de Cys C em pacientes com enxaqueca sem aura. Métodos: Foram incluídos no estudo 80 participantes; 40 pacientes e 40 controles saudáveis. Os níveis séricos de Cys C foram investigados usando o ensaio de imunoabsorção ligado à enzima (enzyme-linked immunosorbent assay - ELISA). A análise estatística foi realizada utilizando o Statistical Package for the Social Sciences (SPSS), versão 22.0 (SPSS Inc, IL, EUA). Resultados: Em nosso estudo, os níveis séricos de Cys C foram encontrados em 73,88 ng/mL no grupo de pacientes e 24,92 no grupo de controle saudável, sendo os níveis significativamente maiores nos pacientes (p=0,000). Os níveis séricos de Cys C foram significativamente diferentes entre faixas etárias no grupo de pacientes (p=0,049). No entanto, a escala visual analógica (EVA) (p=0,707), o tempo de duração da doença (p=0,725) e o índice de massa corporal (p=0,136) não foram significativamente diferentes entre os dois grupos. Conclusão: Nossos achados demonstram que altos níveis séricos de Cys C estão independentemente associados à enxaqueca sem aura. Até onde sabemos, este é o primeiro estudo a determinar os níveis séricos de Cys C em pacientes com enxaqueca e os resultados sugerem que o Cys C sérico pode ser um potencial biomarcador nessa condição clínica.

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