Parâmetros clínicos e laboratoriais de sarcopenia em pacientes com esclerose sistêmica : um estudo de coorte prospectivo

Introdução: A esclerose sistêmica (ES) é uma doença autoimune multissistêmica, de etiopatogenia complexa, com expressão fenotípica heterogênea e prognóstico limitado. Apenas recentemente estudos têm avaliado a prevalência e as associações clínicas da sarcopenia nessa população, e até o momento o seu impacto na morbi-mortalidade pela doença é desconhecido. Objetivo: Investigar as associações diagnósticas e prognósticas de parâmetros clínicos e laboratoriais de sarcopenia e ES. Métodos: Coorte prospectiva incluindo 94 pacientes com ES em seguimento no ambulatório de Reumatologia do Hospital de Clínicas de Porto Alegre (HCPA). ES foi definida de acordo com os critérios de classificação do ACR/EULAR de 2013 ou os critérios para ES precoce propostos por LeRoy e Medsger. Sarcopenia foi definida de acordo com as recomendações do European Working Group on Sarcopenia in Older People (EWGSOP) atualizadas em 2019 (EWGSOP2), com avaliação da força de preensão palmar, avaliação da massa magra por meio de densitometria corporal total e avaliação do desempenho físico por meio do short physical performance battery (SPPB). Os pacientes foram submetidos à avaliação clínica detalhada, ferramentas para rastreamento de sarcopenia e fragilidade, provas de função pulmonar, ecocardiograma e dosagem de irisina, miostatina e activina A séricas por meio da técnica de ELISA na inclusão. Após 3 anos de seguimento, os pacientes foram reavaliados, sendo registrados dados sobre hospitalizações, infecções e óbitos ocorridos no período. Análise de regressão multivariada foi realizada para avaliar fatores independentemente associados à sarcopenia no baseline. Alterações nos parâmetros de sarcopenia ao longo do tempo foram analisadas por equações de estimativa generalizada. Correlação de Pearson ou Spearman foi utilizada para correlacionar os biomarcadores com parâmetros de sarcopenia. Análise de curva ROC (Receiver Operating Characteristic) foi utilizada para análise de biomarcadores contra mortalidade. Análise de sobrevida de Kaplan-Meier foi utilizada para avaliação dos parâmetros de sarcopenia em relação à mortalidade. Resultados: Noventa e quatro pacientes foram acompanhados por uma média de 2,7 anos. A idade média foi de 60,5±10,3 anos e a duração de doença de 13,1±8,2 anos. A prevalência de sarcopenia foi de 15,9% no início do estudo e a sarcopenia foi associada à duração da doença (p=0,004), desnutrição (p=0,03) e úlceras digitais (p=0,038). De acordo com o fenótipo de 8 fragilidade física, 33 pacientes (35,1%) foram considerados frágeis e 53 (56,4%) pré-frágeis. Quatorze pacientes morreram durante o acompanhamento. Ao final do seguimento, houve queda significativa na prevalência de sarcopenia (5,6%, p=0,018) e não foi encontrada associação de sarcopenia com mortalidade, internações, infecções, piora da função pulmonar e novas úlceras digitais. Também houve redução significativa na prevalência de desnutrição (p=0,049), fragilidade (p=0,003) e inatividade física (p>0,001). O índice de atividade revisado do European Scleroderma Trials and Research group (EUSTAR) no baseline foi o único preditor de mortalidade em 3 anos na nossa população (p=0,03) e esse índice não mudou significativamente ao longo do tempo (p=0,838). Com relação aos biomarcadores, os níveis séricos de activina A não foram associados à presença de sarcopenia, nem apresentaram correlação com ASMI e força de preensão manual, contudo os níveis de activina A foram mais elevados entre os óbitos (p0.001). Activity by European Scleroderma Trials and Research group (EUSTAR) revised activity index in the baseline was the only predictor of 3-year mortality in our population (p=0.03) and this index has not significantly changed over time (p=0.838). About biomarkers, activin A was not associated with sarcopenia, nor correlated with ASMI and handgrip strength, but circulating levels of activin A were higher in deceased patients (p<0.001) and ROC curve analysis suggested that a threshold of 363 pg/ml may have a good predictive value for mortality. Conclusion: Sarcopenia is prevalent in patients with long-standing SSc and is associated with malnutrition. In our cohort, no association was found between sarcopenia and 3-year mortality and that may be a consequence of the decrease in the prevalence of sarcopenia, as well as the improvement in nutritional and physical parameters, during follow-up. In addition, our study demonstrates that circulating activin A predicts mortality in patients with SSc

Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis

Introduction: Vascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in lupus nephritis (LN) and can be easily assessed in urine. The aim of this study was to assess urinary soluble VCAM-1 (uVCAM-1) as a biomarker of disease activity and treatment response in LN. Methods: This prospective study enrolled 62 patients with class III, IV or V LN diagnosed within the last 3 years and divided them in two groups: with and without active nephritis at the inclusion, each group with 31 patients. At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was assessed. Results: Median uVCAM-1 level was elevated in patients with active compared to inactive LN (P < 0.001). The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and specificity (74.2%) for the diagnosis of active LN. A significant correlation was found between uVCAM-1 level and renal activity scores and traditional biomarkers of LN. The level of uVCAM-1 dropped in patients with active LN who went into remission (P < 0.001), increased in patients who went into activity (P = 0.002) and did not change in patients who remained inactive (P = 0.797). The level of uVCAM-1 peaked during the flare of LN (P < 0.05). Conclusion: The uVCAM-1 is a reliable biomarker that reflects renal disease activity and is useful for monitoring individual patients with lupus nephritis over time

Flow cytometry evaluation of CD14/CD16 monocyte subpopulations in systemic sclerosis patients : a cross sectional controlled study

Background: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by vasculopathy and fibrosis, which can be subclassified into diffuse cutaneous (dSSc) and limited cutaneous (lSSc) subtypes. Previous studies suggest that an increase in monocytes can be a hallmark of various inflammatory diseases, including SSc. Our aim was to evaluate circulating blood monocyte subpopulations (classical, intermediate and non-classical) of SSc patients and their possible association with disease manifestations. Methods: Fifty consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in a cross-sectional study. Monocyte subpopulations were identified based on their expression of CD64, CD14 and CD16, evaluated by flow cytometry, and were correlated with the clinical characteristics of the patients; furthermore, the expression of HLA-DR, CD163, CD169 and CD206 in the monocytes was studied. Thirty-eight age- and sex-matched healthy individuals were recruited as a control group. Results: SSc patients had an increased number of circulating peripheral blood monocytes with an activated phenotypic profile compared to healthy subjects. Absolute counts of CD16+ (intermediary and non-classical) monocyte subpopulations were higher in SSc patients. There was no association between monocyte subpopulations and the clinical manifestations evaluated. Conclusion: We identified higher counts of all monocyte subpopulations in SSc patients compared to the control group. There was no association between monocyte subpopulations and major fibrotic manifestations. CD169 was shown to be more representative in dSSc, being a promising marker for differentiating disease subtypes

Morphological parameters in quadriceps muscle were associated with clinical features and muscle strength of women with rheumatoid arthritis : a cross-sectional study

Background: Rheumatoid arthritis (RA) is an autoimmune, inflammatory and chronic disease that may lead to loss of muscle mass, muscle strength and decreased functionality. Our objectives are to assess the quadriceps muscle morphology by ultrasound (MU) and verify its associations with clinical features, muscle strength and physical function in RA patients. Methods: In this cross-sectional study, RA women ( 18 years) were included. Morphological parameters in quadriceps muscle consisted of the muscle thickness and pennation angle of rectus femoris (RF), vastus intermedius (VI) and vastus lateralis (VL). RA activity was measured by a 28-joint disease activity score (DAS28), muscle strength by handgrip and chair stand tests, and physical function by health assessment questionnaire (HAQ), timed-up-and-go (TUG) test and short physical performance battery (SPPB). Results: Fifty-five patients were included (age: 56.73 9.46 years; DAS28: 3.08 1.29). Muscle thickness in RF, VI and VL were negatively associated with age (RF, p < 0.001; VI, p = 0.013; VL, p = 0.002) and disease duration (RF, p < 0.001; VI, p = 0.005; VL, p = 0.001), and were positively associated with handgrip strength (RF, p = 0.015; VI, p = 0.022; VL, p = 0.013). In addition, decreased muscle thickness in VI (p = 0.035) and a smaller pennation angle in RF (p = 0.030) were associated with higher DAS-28 scores. Conclusion: Quadriceps muscle morphology by ultrasound appears to be affected by age, disease duration, disease activity and muscle strength in patients with RA. MU can be a useful method to evaluate the impact of the disease on skeletal muscle