The aim of this study was to define the clinical associations of anti-endothelial cell antibody (AECA) in systemic lupus erythematosus (SLE) patients by measuring serum AECA titers to correlate with the disease activity and clinical manifestations. Forty-one SLE patients and 27 controls were studied. Serum samples were collected at the time of patient presentation with disease exacerbation and 4 weeks after the start of treatment. The disease activity was evaluated by the SLE Disease Activity Index (SLEDAI). AECA was detected by enzyme-linked immunosorbent assay (ELISA) methods with the surface antigen of the immortalized human microvascular endothelial cell line (HMEC-1). The mean immunoglobulin (Ig)G-AECA and IgM-AECA optical densities (ODs) were significantly higher in patients with SLE compared with controls [mean +/- standard deviation (SD), 0.32 +/- 0.15 vs 0.18 +/- 0.16 and 0.29 +/- 0.14 vs 0.21 +/- 0.09, respectively]. There was a positive correlation between IgG-AECA and the SLEDAI scores. The positivity rate of AECA in the groups with digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody was significant. In conclusion, AECA may be involved in the pathogenesis of SLE and was correlated with the disease activity. It was also associated with clinical manifestations such as digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody positivity.
PurposeFoxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes.Materials and MethodsTestes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed.ResultsFoxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter.ConclusionFOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.
Panhypogammaglobulinaemia is a rare complication of systemic lupus erythematosus (SLE), but its cause and mechanism are unclear. We observed transient panhypogammaglobulinaemia in a patient with neuropsychiatric SLE after treatment with prednisolone and cyclophosphamide. After the patient developed recurrent infections, laboratory findings disclosed panhypogammaglobulinaemia with B-lymphocyte deficiency. The serum immunoglobulin level returned to the normal range after the prednisolone was tapered off. Because lupus patients are susceptible to infections associated with disease exacerbation or immunosuppressive treatment, recurrent infections might be expected during the disease course without need for further evaluation of the immunodeficiency. However, this reversible, probably drug-induced case of hypogammaglobulinaemia highlights the need for immunoglobulin measurements when immunodeficiency is suspected in lupus patients.
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