Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients.

INTRODUCTION: AIM2 inflammasome activation leads to the release of IL-ß, which plays an important role in rheumatoid arthritis pathogenesis. In this work, we evaluated AIM2 expression and activity in RA patients and healthy controls. METHODS: AIM2 and RANKL expression were evaluated by flow cytometry. Inflammasome activity was determined in monocyte cultures stimulated with synthetic DNA by measuring IL-1ß levels in supernatants using an ELISA assay. The caspase-1 expression in monocytes was measured by western blot, the POP3 expression was analysed by qPCR, and serum levels of IFN-γ were evaluated using ELISA assay. RESULTS: We observed a diminution of CD14+AIM2+ cells in RA patients, associated with disease activity and evolution. Likewise, the levels of IL-1ß were increased in monocyte cultures un-stimulated and stimulated with LPS from RA patients with DAS28 ≥ 4. The Caspase-1 activity and RANKL + monocytes in RA patients were slightly increased. Finally, augmented POP3 expression and diminished IFN-γ serum levels were detected in RA patients. CONCLUSION: Our results showed that the monocytes from RA patients were prone to release IL-1ß in the absence of the AIM2 inflammasome signal. The down-regulation of AIM2 to a systemic level in RA patients might be a consequence of augmented POP3 expression and might imply the survival of pro-inflammatory cells contributing to the inflammation process.

Invasive fungal infections in patients with systemic lupus erythematosus.

OBJECTIVE: Invasive fungal infections (IFI) are catastrophic diseases associated with a high mortality. Relatively few cases of IFI have been described in systemic lupus erythematosus (SLE) and their related factors have not been completely explored. We evaluated factors associated with IFI in patients with SLE. METHODS: All patients with both IFI and SLE admitted to our hospital in the last 7 years were evaluated and each was compared with 5 hospitalized patients with SLE (controls). Demographic factors, duration of SLE, and treatment in the previous month were compared. RESULTS: Sixty patients with SLE were evaluated (10 with IFI and 50 controls). Median age was 29 years. High C-reactive protein levels were associated with IFI, along with other factors such as high disease activity, mechanical ventilation, treatment with antibiotics, hemodialysis, high doses of glucocorticoids (GC), and treatment with mycophenolate mofetil. Mortality was 4 times more frequent in patients with IFI than in SLE patients without the deep fungal infection. CONCLUSION: IFI is a rare infection observed in patients with rheumatic diseases. We describe factors associated with IFI in patients with SLE. IFI is associated with elevated morbidity and mortality. Early diagnosis and treatment are desirable.

The His155Tyr (489C>T) single nucleotide polymorphism of P2RX7 gene confers an enhanced function of P2X7 receptor in immune cells from patients with rheumatoid arthritis.

We assessed the possible association between several single nucleotide polymorphisms (SNP) of P2RX7 gene with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We determined the function of P2X7 receptor and the frequency of the 489C>T, 1096C>G, and 1513A>C SNP of P2RX7 gene in 111 and 122 patients with SLE and RA, and 98 healthy subjects. We found no significant association between the SNPs studied and SLE or RA. We also detected that lymphocytes from SLE and RA patients with the 489C>T SNP showed a higher ethidium bromide uptake in response to ATP than wild type or 1096C>G/1513A>C subjects. In addition, cells from RA patients and the 489C>T genotype, showed higher [Ca(2+)]i responses to ATP. Our data indicate that the 489C>T SNP of P2RX7 gene confers an enhanced function of this receptor in patients with RA, which may contribute to the pathogenesis of this condition.

Expression and function of the P2X(7) purinergic receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.

Because the synthesis of pro-inflammatory cytokines and apoptosis of lymphoid cells can be induced through P2X(7), we decided to study its expression, function (apoptosis, shedding of CD62L and synthesis of IL-1beta induced by ATP) and genetic polymorphisms (1513 AC and -762 T/C) in peripheral blood mononuclear cells from 101 patients with systemic lupus erythematosus (SLE), 122 with rheumatoid arthritis (RA) and 90 healthy controls. We found no significant differences in the distribution of 1513 and -762 genotypes of P2X(7) gene in SLE or RA patients compared with healthy controls. However, a diminished induction of apoptosis of CD4(+) T lymphocytes and monocytes was observed in SLE patients with the 1513 AC genotype, and the release of IL-1beta upon stimulation with ATP was significantly decreased in SLE patients. In contrast, in RA patients we detected that the release of IL-1beta was increased. In addition, in patients with SLE and RA the SNPs 1513 AC was associated with a low expression of P2X(7). These results suggest a possible involvement of P2X(7) in the pathogenesis of inflammatory autoimmune diseases.

Moléculas de adhesión celular y piel / Adhesion molecules and skin

Las moléculas de adhesión celular tienen un papel importante en múltiples fenómenos biológicos, tanto normales (generación de la respuesta inmune, coagulación, cicatrización, órgano-génesis) como patológicos (inflamación, trombosis, metástasis de células tumorales). En el presente trabajo se revisan los aspectos básicos de las moléculas de adhesión celular y su papel en diversas condiciones patológicas que afectan a la piel

Autoeccematización en un paciente con dermatitis por contacto / Autoeczematization in a patient with contact dermatitis

Se presenta el caso de un paciente con dermatitis por contacto con autoeccematización. Se hace referencia a la inmunopatogenia de esta condición, la cual parece consistir en un fenómeno de autoinmunidad de tipo celular hacia antígenos epidérmicos autólogos

Herpes zoster: presentación de dos casos / Herpes Zoster: presentation of two clinical cases

El herpes zoster es una infección aguda, causada por el virus de la varicela zoster (VZV), que se manifiesta clínicamente por la aparición de vesículas umbilicadas, limitadas a un dermatoma, acompañándose de dolor y en ocasiones de malestar general. Se describen dos casos clínicos de herpes zoster con presentaciones atípicas. El reconocimiento temprano de las lesiones es necesario para tratar de evitar complicaciones del tipo de la neuralgia posherpética o bien la cicatrización residual

Informe de un caso de síndrome de Sweet asociado a tumores sólidos / Report of a Sweet's syndrome associated to a solid tumor

El síndrome de Sweet (SS) ha sido ocasionado con neoplasias hematológicos y en menor grado con tumores sólidos; la patogénesis aún no se ha dilucidado, sin embargo, hay evidencias a favor de mecanismos inmunopatogénicos. Se presenta un caso clínico de un paciente con SS y se revisan los factores que actualmente han sido involucrados en su patogenia