A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency To the Editor:Recently, a novel syndrome of combined immunodeficiency, allergy, and ''auto''inflammation caused by mutations in the ARPC1B gene has been reported. [1][2][3][4] Analysis of patient-derived

BackgroundFumaric acid esters (FAE) are a group of compounds which are currently under investigation as an oral treatment for relapsing-remitting multiple sclerosis. One of the suggested modes of action is the potential of FAE to exert a neuroprotective effect.Methodology/Principal FindingsWe have investigated the impact of monomethylfumarate (MMF) and dimethylfumaric acid (DMF) on de- and remyelination using the toxic cuprizone model where the blood-brain-barrier remains intact and only scattered T-cells and peripheral macrophages are found in the central nervous system (CNS), thus excluding the influence of immunomodulatory effects on peripheral immune cells. FAE showed marginally accelerated remyelination in the corpus callosum compared to controls. However, we found no differences for demyelination and glial reactions in vivo and no cytoprotective effect on oligodendroglial cells in vitro. In contrast, DMF had a significant inhibitory effect on lipopolysaccharide (LPS) induced nitric oxide burst in microglia and induced apoptosis in peripheral blood mononuclear cells (PBMC).ConclusionsThese results contribute to the understanding of the mechanism of action of fumaric acids. Our data suggest that fumarates have no or only little direct protective effects on oligodendrocytes in this toxic model and may act rather indirectly via the modulation of immune cells.

In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination.

Background Rare nodules of heterotopic adrenocortical and hepatic tissue are reported in the placenta. A mechanism for adrenocortical tissue in the placenta has been perplexing, while hepatic tissue is generally considered related to yolk sac primordia. The clear cell morphology of these nodules is similar to the adrenal cortex of the adult; however, the fetal adrenal gland does not usually display clear cells. Methods We stained 9 placental nodules, histologically identical to “adrenocortical” heterotopia of the placenta, to determine whether adrenocortical differentiation could be confirmed. These cases include 3 archival cases initially diagnosed as “adrenocortical” heterotopia. Results Immunohistochemical staining with steroid factor-1 (SF-1), HepPar-1, and Arginase-1 showed that these nodules of clear cells are actually hepatic (SF-1 negative, HepPar-1, and Arginase-1 positive). PAS staining suggests that glycogen accumulation is responsible for the clear cytoplasm. In contrast, a nodule of adrenocortical heterotopia near the testis and the adrenal gland from a 38-week-old neonatal autopsy case confirm SF-1 reactivity as expected. Conclusion We propose that adrenocortical heterotopia in the placenta is a misnomer, and that these subchorionic nodules of clear cells demonstrate hepatic differentiation.

Lupus mastitis is a rare complication of systemic or discoid lupus erythematosus with an uncommon initial presentation when limited to the breast. In this article, we report a 42-year-old woman who presented with constant pain and tenderness in her breasts. Ultrasound imaging of the left breast revealed a 14-mm oval mass, suspicious for malignancy; a needle core biopsy was performed. Sections showed necrosis of the fat lobules with associated mixed nodular lymphoplasmacytic aggregates. Karyorrhectic debris, fibrinoid necrosis of small vessels, and microcalcifications were all present while the background breast parenchyma was unremarkable. The diagnosis of lupus mastitis was rendered. Subsequent serology showed negative dsDNA but positive antinuclear antibodies, C4, and anti -Sjögren';ssyndrome-related antigen A antibodies. Clinical features of active systemic disease were not identified at the patient's follow-up dermatology appointment 1 month after the biopsy, and she elected management for her nodules with steroids. To the best of our knowledge, only 40 other cases of lupus mastitis have been reported in the English literature, of which 25 presented as a mass and only in 6 lupus mastitis of the breast was the initial presentation. In conclusion, we bring much needed awareness to lupus mastitis as the first presentation of disease.