Expression of serotonergic receptors in psoriatic skin

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.     

BDNF in RA: Downregulated in plasma following anti-TNF treatment but no correlation with inflammatory parameters

The involvement of brain-derived neurotrophic factor (BDNF) in rheumatoid arthritis (RA) is largely unknown. The distribution of BDNF and its associated receptors, TrkB and p75, in the synovial tissue of patients with RA was examined and contrasted with that in patients with osteoarthritis (OA). Additionally, levels of BDNF in both synovial tissue and synovial fluid were measured. Furthermore, the effects of anti-tumour necrosis factor (anti-TNF; infliximab) treatment on BDNF levels in the plasma of RA patients were analysed. Cells in the synovium showed immunoreactivity for BDNF and BDNF-, p75- and TrkB-receptor immunoreactions were seen in nerve fibres of nerve fascicles and in association with sensory corpuscles. The levels of BDNF in synovial tissue were not correlated with the number of inflammatory cells observed microscopically or with levels of TNFα. Nor did the BDNF levels in synovial fluid correlate with erythrocyte sedimentation rate (ESR) or white blood cell counts. Anti-TNF treatment lead to a decrease in plasma levels of BDNF 14 weeks after the initiation of anti-TNF therapy, i.e., 8 weeks after the last infusion. Higher levels of BDNF were observed in RA patients at baseline compared with those for healthy individuals. However, the levels of BDNF in plasma of patients treated with anti-TNF did not correlate with the changes in ESR or a disease activity score. The clinical significance of this study is that anti-TNF treatment influences plasma levels of BDNF although there was no evidence that BDNF levels correlate with inflammatory parameters in either infliximab-treated or non-infliximab-treated patients with RA. Instead it is likely that sources other than inflammatory cells, including nerve structures, are important sources of BDNF and that the effects of anti-TNF treatment on BDNF levels may be related to effects on circulating and various local cells and/or BDNF-containing neurons.     

Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients,their first-degree relatives,and healthy controls

Objective

Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs.

Method

MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied.

Results

Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p?=?0.020), miR-26b-5p (p?=?0.018), miR-142-3p (p?=?0.005), and miR-155 (p?=?0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression.

Conclusions

We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed.

Erythema toxicum neonatorum is an innate immune response to commensal microbes penetrated into the skin of the newborn infant

Erythema toxicum neonatorum is a common rash of unknown etiology affecting healthy newborn infants. In this study, we postulated that the rash reflects a response to microbial colonization of the skin at birth, and that the hair follicle constitutes an "easily opened door" for microbes into the skin of the newborn. We collected microbial cultures from the skin of 69 healthy, 1-d-old infants with and without erythema toxicum to identify the colonizing flora and correlate culture results with clinical findings. We also analyzed biopsies from lesions of erythema toxicum with scanning and transmission electron microscopy in the search for microbes. Finally, each infant's body temperature was measured as a sign of acute phase response. We found that 84% of 1-d-old healthy infants, with and without erythema toxicum were colonized with coagulase-negative staphylococci. In all lesions of erythema toxicum, TEM identified cocci-like bacteria localized in the hair follicle epithelium and into recruited immune cells surrounding the hair follicle; morphology and dimension supported their identification as belonging to the genus Staphylococcus. SEM revealed 10 times more hair structures per skin surface unit in newborns compared with adults. Infants with erythema toxicum also had higher body temperature. In erythema toxicum, commensal microbes gain entry into the skin tissue, most probably through the hair canal. This triggers the local immune system and a systemic acute phase response, including an increase in body temperature. We speculate that early microbial exposure to the newborn may be important for the maturation of the immune system.