FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors

[EN] Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other Fc?R functional polymorphisms. Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. Results: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). Conclusion: None of the three functional polymorphisms in Fc?R genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies

Prevención y diagnóstico precoz de osteoporosis infantil: ¿estamos haciendo lo correcto?

Objetivos: Evaluar la prevención, el diagnóstico precoz y la formación recibida de la osteoporosis en la Pediatría de nuestro medio. Material y métodos: Encuesta dirigida a facultativos de Pediatría de Atención Primaria (AP) y Atención Especializada (AE) que valora su actividad en prevención, detección y formación recibida en osteoporosis, y que fue difundida a través de las sociedades científicas pertinentes. Resultados: Participaron 420 pediatras (324 de AP y 96 de AE). El 93,5% de los pediatras de AP y el 89,6% de los de AE valoraban la actividad física de los pacientes; el 85,19% y 35,4% de ellos, respectivamente, la ingesta de lácteos. El 45,68% de AP y el 70,2% de AE suplementaban con calcio y vitamina D ante aporte nutricional bajo, realizándoles seguimiento el 39,2% de AP y el 47,2% de AE. El 39,6% de pediatras de AE solicitaba densitometría ósea ante enfermedad o tratamiento de riesgo, y el 47,9% medía los niveles de 25-OH-vitamina D. El 25,93% de AP y el 45,3% de AE preguntaban por la existencia de fracturas, el 90,4% y 96,8% valoraban el mecanismo etiopatogénico. El 40% de AP y el 86,2% de AE solicitaban una densitometría ósea o derivaban al especialista ante fracturas por traumatismos de baja energía, con criterios específicos en el 13,7% y 5,86%, respectivamente. El 92% de AP y el 82,3% de AE no habían recibido formación reciente en osteoporosis infantil. Conclusión: La detección, los circuitos de derivación y la formación de los pediatras respecto a la salud ósea en nuestro país es mejorable. Optimizar estos aspectos es fundamental para favorecer el pico de masa ósea en nuestra población

FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors

Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other Fc gamma R functional polymorphisms. Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. Results: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). Conclusion: None of the three functional polymorphisms in Fc gamma R genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies

Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis

OBJECTIVES: We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF). METHODS: A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included sex, inhibitors of TNF, and baseline DAS28 as covariates. RESULTS: Significant association was found between the FCGR2A H131R polymorphism and the response to treatment with INX, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P=0.04-0.008 at different times) in the first set of patients and confirmed in the second group of patients (P=0.026 at 3 months of follow-up). Association was also found in the comparison between nonresponders and responders to INX by the EULAR criteria. CONCLUSION: We found an association of the FCGR2A 131R allele with poor response to INX. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for INX response prediction

Benefits of employment in people with mental illness: Differential mediating effects of internalized stigma on self‐esteem

Previous research shows a negative relationship between the stigmatization of people with mental illness and self-esteem. Through path analysis, the present study examines the extent to which both perceived individual discrimination and perceived group discrimination predict self-esteem and the extent to which internalized stigma and concealment mediate these relationships. We also test whether this mediation is moderated by the amount of time worked. The participants were 110 Spanish people with mental illness (67 men and 43 women) recruited from Spanish nongovernmental organizations. The sample was divided into two groups according to whether they had a permanent employment contract (which occurs when a person has worked for over 5 months). The results confirmed the mediating role of internalized stigma between individual perceived discrimination and self-esteem in the group with permanent employment contracts. Group discrimination had an indirect positive association with self-esteem through reduced internalized stigma in the whole sample. In sum, our results show that being employed for longer may strengthen the relationship between perceived individual discrimination and self-esteem via internalized stigma and that perceived group discrimination may buffer the negative relationship between internalized stigma and self-esteem in people with mental illness