The distribution of clinical findings in Bechterew's syndrome (ankylosing spondylitis) suggests distinct genetic subgroups

One hundred and twenty-two consecutive patients hospitalized for ankylosing spondylitis (AS) were reexamined. The frequency of clinical signs and results of tests for associations are presented. Psoriasis was associated with a distal pattern of peripheral arthropathy. Spinal rigidity was predominantly seen in males. Males with phalangeal arthropathy exhibited preserved spinal mobility. This was the case also when HLA B27 positives and patients who did not have psoriasis were considered separately. HLA B27 positive patients in this group had frequently experienced acute anterior uveitis. It seems possible that the disease in such males is the result of combined predisposition to ankylosing spondylitis and psoriatic arthropathy. Hip arthropathy was frequently present in males with spinal rigidity. The associations observed confirm that AS is a heterogenous group of diseases. The term "syndrome" may be suitable for such a heterogenous group, and we prefer the term "Bechterew's syndrome" as the name of this group. When these new findings are added to the previous observations that acute anterior uveitis probably is a clinical, sex-influenced characteristic of HLA B27 positive Bechterew's syndrome, that HLA B27 negative patients with Bechterew's syndrome frequently had psoriasis and were HLA B13 and B17 negative, and that psoriasis was frequent in HLA B27 positive patients as well, we tentatively conclude that different and interacting genetic mechanisms may be involved in the etiology of Bechterew's syndrome.     

The relationship between smoking,psoriasis and psoriatic arthritis

Introduction: Smoking is the single most important cause of preventable mortality worldwide. Besides being associated with major cardiovascular and bronchopulmonary diseases, and several cancers, it has been linked with a number of immune-related conditions, including psoriasis and psoriatic arthritis (PsA)

We aimed to summarize data on the role of smoking in the development and prognosis of psoriasis and PsA, pointing to the consequences in terms of disease management.

Areas covered: Mechanisms, clinical manifestations, and comorbidities associated with smoking in psoriasis and PsA were reviewed by searching Medline, Embase and Cochrane Library databases for papers published between January 2000 and July 2018 using combination of terms. Articles not written in English were excluded.

Expert commentary: Smoking is a risk factor for psoriasis development. As for PsA, smoking is positively associated with the disease at the population level, but it is negatively associated in patients with psoriasis. This phenomenon is referred to as the ‘smoking paradox’ of PsA. Smoking may cause poor response and reduced adherence to treatment of both psorasis and PsA. Physicians need to be aware of the smoking habits of their patients with psoriasis and PsA; whenever possible, smoking cessation programs should be considered.     

重组人白细胞介素10对角朊细胞增殖及产生细胞因子的影响

目的：研究重组人白细胞介素10(rhIL-10)对无血清培养的角朊细胞增殖和产生细胞因子的影响，探讨其治疗银屑病的作用机制。方法：用四甲基偶氮唑蓝比色法(MTT)测定其对细胞增殖的影响；小鼠胸腺细胞增殖法检测白细胞介素1(IL-1)；ELISA法检测白细胞介素6(IL-6)、白细胞介素8(IL-8)。结果：重组人白细胞介素10抑制角朊细胞增殖与IL-1、IL-6及IL-8的分泌，并呈剂量依赖关系。结论：重组人白细胞介素10抑制角朊细胞与细胞因子分泌，可能是治疗银屑病的作用机理之一．     

rhIL-10对银屑病动物模型的治疗作用及免疫功能的影响

目的　研究重组人白细胞介素 10 (rhIL 10 )对银屑病动物模型的治疗作用以及免疫功能的影响。方法　用小鼠雌激素期阴道上皮模型、鼠尾鳞片表皮模型观察重组人白细胞介素 10的抗银屑病作用 ,并检测ConA诱导T淋巴细胞增殖、LPS诱导B淋巴细胞增殖、NK细胞活性及细胞因子(IFN γ、IL 2、IL 1、TNF α)水平。结果　rhIL 10 (5 ,2 0 ,80μg·kg-1·d-1,sc)对小鼠阴道上皮细胞有丝分裂有抑制作用 ,促进小鼠尾鳞片颗粒层的形成。对ConA诱导T淋巴细胞增殖反应及IL 2、IFN γ产生有抑制作用 ;对LPS诱导小鼠腹腔巨噬细胞产生IL 1、TNF α具有抑制作用 ;对NK细胞活性有抑制作用 ;对LPS诱导B淋巴细胞增殖有促进作用。结论　rhIL 10可能是通过抑制表皮细胞增殖与促进其分化 ,并参与抗炎与免疫调节过程而发挥治疗银屑病动物的作用     

Current Concepts in Rheumatology,Royal Society of Medicine

Ustekinumab is a fully human monoclonal antibody directed against the p40 subunit shared by interleukin 12 and interleukin 23, two naturally occurring protein regulators that play an important role in immune-mediated inflammatory diseases, including psoriatic arthritis (PsA). In September of 2009, the US FDA approved ustekinumab for the treatment of adult patients with moderate to severe plaque psoriasis. Beginning in November of 2009, Janssen Biotech (formerly Centocor Biotech), the developer of ustekinumab, initiated clinical trials to investigate the efficacy of ustekinumab in the treatment of other inflammatory disorders, including PsA. Phase II and Phase III studies showed both a good safety profile and significant efficacy for ustekinumab in the treatment of PsA, leading to the drug's approval in both Europe and the USA. In an immunotherapy market currently dominated by anti-TNF-α drugs for the treatment of PsA, ustekinumab offers an alternative option for patients with PsA, including those unresponsive to methotrexate and the TNF-α inhibitory agents currently approved for this potentially debilitating disease.     

mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target

In this short communication we are providing insight about the regulatory role of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) kinase system in psoriatic disease. This is an upcoming active research field in respect to elucidating the inflammatory and proliferative cascades of psoriatic disease. To provide a new dimension to the understandings of the molecular principles of the pathogenesis of autoimmune diseases, we hypothesized that (i) dysregulation of cytokines and growth factors in autoimmune diseases activate the mTOR signaling system and (ii) the activated mTOR kinase system is a key regulator of the inflammatory/proliferative cascades of the disease process. In support of this hypothesis we have earlier reported that growth factors (nerve growth factor (NGF) and platelet-derived growth factor (PDGF)) and relevant cytokines (interleukin (IL)-17, IL-22) known to be critical for psoriasis, psoriatic arthritis, and rheumatoid arthritis activate the mTOR signaling system. Here, we are providing our latest observations that the mTOR signaling proteins are upregulated in psoriatic skin and further we observed that proliferation of keratinocytes (KC) and synovial cells (synovial fibroblasts (FLS)) of psoriatic arthritis are dependent on the PI3K-AKT-mTOR kinase system. To our knowledge, we are the first to explore whether a double kinase inhibitor of mTOR signal proteins has a therapeutic potential for psoriatic disease. Here we will be sharing our views, our research work in this field and as well we will provide evidences how a double kinase inhibitor of mTOR signal proteins can be an effective therapeutic agent for psoriatic disease.     

Silencing of homeobox A5 gene in the stratum corneum of psoriasis

Analysis of psoriatic parakeratotic cells is helpful for understanding the pathogenesis of psoriasis. Methylation analysis can be performed on psoriatic scales, but it is unclear whether genes can be silenced by DNA methylation in psoriatic stratum corneum. The present study was conducted to detect genes silenced in psoriatic stratum corneum. Methylation array analysis with 485 577 probes, quantitative real‐time methylation‐specific PCR (RT‐MSP) and bisulphite sequencing were performed for 30 psoriatic scale samples, 6 fully developed psoriatic skin samples and 12 normal skin samples. Immunohistochemical staining of HOXA5 was performed for 29 psoriatic epidermal samples and 13 normal epidermal samples. The genome‐wide methylation array detected two CpG sites within CpG islands (CGIs) located in promoter regions of HOXA5 and LIAS that had methylation levels of >0.6 in at least one of the three psoriatic scale samples and of <0.2 in all three normal skin tissue samples (methylation rate range, 0.0‐1.0). RT‐MSP for HOXA5CGI, in which the primers were successfully developed, revealed that the average methylation level of 27 psoriasis scales (60.2%) is significantly higher than that of 9 normal skin samples (34.6%) (P=.013). Immunohistochemical staining revealed that HOXA5 protein was not expressed in the stratum corneum of fully developed psoriatic epidermis, but the protein was expressed in the stratum corneum of incompletely developed epidermis and normal epidermis. In conclusion, HOXA5 can be silenced in the stratum corneum of psoriasis. The silenced gene was identified by non‐invasive methylation analysis of psoriatic scales.     

Rapid spread of mannan to the immune system,skin and joints within 6 hours after local exposure

Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA- and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [¹⁸F]. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within 6 h after intraperitoneal injection. The time it took to transport mannan, and its presence in blood, indicated cellular transport of mannan within the circulatory system. In addition, mannan was filtered mainly through the spleen and liver. [¹⁸F]fluoromannan was excreted via kidneys, small intestine and, to some extent, the mouth. In conclusion, mannan reaches joints rapidly after injection, which may explain why mannan-induced inflammatory disease is targeted to these tissues.     

Itching for an answer: A review of potential mechanisms of scalp itch in psoriasis

Scalp psoriatic itch is a common complaint and often poses a therapeutic challenge. The pathophysiology of this phenomenon is unclear. The unique anatomy of the scalp contains richly innervated hair follicles, abundant vasculature and perifollicular inflammatory cytokines which may all contribute to this common sensory complaint. The mast cell, in particular, is portrayed as one of the main itch conductors for its ability to trigger neurogenic inflammation, activate the peripheral hypothalamic‐pituitary‐adrenal‐axis, process and integrate itch signalling through its interactions with the scalp hair follicles. Herein, we explain and speculate upon potential mechanisms underlying itchy scalp psoriasis, involving interconnections between the neuroimmune, neurovascular and neuroendocrine systems. Many factors may play roles in itchy scalp psoriasis including the scalp hair structure, immune system, endocrine system, nervous system and vascular system. These may warrant further exploration as therapeutic targets that go beyond the application of mere anti‐inflammatory agents.