PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas.

The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4+ and CD8+ T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death. Moreover, double-deficiency in PARP-1/PARP-2 in T-cells led to highly aggressive T-cell lymphomas with long latency. Our findings establish a coordinated role of PARP-1 and PARP-2 in T-cell homeostasis that might impact on the development of PARP-centred therapies.

Undetectable pre-ablation thyroglobulin levels in patients with differentiated thyroid cancer: it is not always what it seems.

OBJECTIVE: To establish the frequency of U Tg (undetectable pre-ablation thyroglobulin) in TgAb- negative patients and to evaluate the outcome in the follow-up. SUBJECTS AND METHODS: We retrospectively reviewed 335 patients' records. Twenty eight patients (9%) had U Tg. Mean follow-up was 42 ± 38 months. All subjects had undergone total thyroidectomy, and lymph nodes were positive in 13 (46%) patients. Tg and TgAb levels were measured 4 weeks after surgery by IMA technology in hypothyroid state. No evidence of disease (NED) status was defined as undetectable (< 1 ng/mL) stimulated Tg and negative Tg-Ab and/or negative WBS, together with normal imaging studies. RESULTS: Seventeen patients (61%) were considered with NED. Four patients (14%) had persistent disease (mediastinum, n = 1, lung n = 2, unknown n = 1), and 7 (25%) had detectable TgAb by other method during their follow-up. CONCLUSIONS: U Tg levels usually is associated to a complete surgery. However, in a low percentage of patients, this may be related to false negative Tg or TgAb measurement.

Undetectable pre-ablation thyroglobulin levels in patients with differentiated thyroid cancer: it is not always what it seems / Níveis indetectáveis de tireoglobulina pré-ablação em pacientes com câncer de tireoide: nem sempre é o que parece

OBJECTIVE: To establish the frequency of U Tg (undetectable pre-ablation thyroglobulin) in TgAb- negative patients and to evaluate the outcome in the follow-up. SUBJECTS AND METHODS: We retrospectively reviewed 335 patients' records. Twenty eight patients (9%) had U Tg. Mean follow-up was 42 ± 38 months. All subjects had undergone total thyroidectomy, and lymph nodes were positive in 13 (46%) patients. Tg and TgAb levels were measured 4 weeks after surgery by IMA technology in hypothyroid state. No evidence of disease (NED) status was defined as undetectable (< 1 ng/mL) stimulated Tg and negative Tg-Ab and/or negative WBS, together with normal imaging studies. RESULTS: Seventeen patients (61%) were considered with NED. Four patients (14%) had persistent disease (mediastinum, n = 1, lung n = 2, unknown n = 1), and 7 (25%) had detectable TgAb by other method during their follow-up. CONCLUSIONS: U Tg levels usually is associated to a complete surgery. However, in a low percentage of patients, this may be related to false negative Tg or TgAb measurement.

OBJETIVO: Estabelecer a frequência de U Tg (tireoglobulina indetectável pré-ablação) em pacientes com TgAb negativo e avaliar o prognóstico no seguimento. SUJEITOS E MÉTODOS: Foram analisados retrospectivamente 335 registros de pacientes. Vinte e oito pacientes (9%) tiveram U Tg. O acompanhamento médio foi de 42 ± 38 meses. Todos os participantes receberam uma tireoidectomia total, e os linfonodos foram positivos em 13 (46%) pacientes. Tg e TgAb foram medidos quatro semanas após a cirurgia pelo método IMA em estado de hipotireoidismo. A não evidência de doença (NED) foi definida como níveis indetectáveis (<1 ng/mL) de Tg estimulada com anticorpos anti-Tg negativos e/ou PCI negativo, com estudos de imagem normais. RESULTADOS: Dezessete pacientes (61%) foram considerados com NED. Quatro pacientes (14%) tiveram doença persistente (mediastino, n = 1, pulmão n = 2, n = desconhecido 1), e 7 (25%) apresentavam anticorpos anti-Tg detectáveis por outro método durante acompanhamento. CONCLUSÕES: U Tg geralmente indica uma cirurgia completa. No entanto, em uma pequena porcentagem de pacientes, pode estar relacionada com uma medida de Tg ou de anticorpos anti-Tg falsamente negativos.