Satoshi Morioke

Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria

To cite this article: Takahagi S, Mihara S, Iwamoto K, Morioke S, Okabe T, Kameyoshi Y, Hide M. Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria. Allergy 2010; 65: 649–656.

Fucoidan suppresses IgE production in peripheral blood mononuclear cells from patients with atopic dermatitis.

We previously reported that fucoidan, a dietary fiber purified from seaweed, inhibited IgE production in B cells from mice spleen in vitro and ovalbumin-sensitized mice in vivo. In this study, we examined the effect of fucoidan on IgE production in human peripheral blood mononuclear cells (PBMC) in vitro. PBMC, obtained from healthy donors or patients with atopic dermatitis (AD) with high levels of serum IgE, were cultured with IL-4 and anti-CD40 antibody in the presence or absence of fucoidan. Fucoidan significantly reduced IgE production in PBMC without affecting cell proliferation and IFN-γ production. Fucoidan also inhibited immunoglobulin germline transcripts of B cells in PBMC, and decreased the number of IgE-secreting cells. The inhibitory effects of fucoidan were similarly observed for both PBMC from patients with AD and those with healthy donors. Our findings indicate that fucoidan suppresses IgE induction by inhibiting immunoglobulin class-switching to IgE in human B cells, even after the onset of AD.

Increased thrombin generation potential in patients with chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a common skin disorder of unknown etiology characterized by spontaneously appearing wheals and pruritus for six weeks or longer. Recent studies have supported an autoimmune origin in a population of patients with CSU. Circulating autoantibodies against the high affinity IgE receptor (FcεRI) and IgE are able to causemast cell degranulation.1 On the other hand, the possible involvement of the blood coagulation system has emerged.2 This notion was supported by moderate increases of several coagulation markers, such as prothrombin fragment 1þ2 (PF1þ2), fibrin degradation products (FDP) and Ddimer in correlation with clinical severity, and the efficacy of anti-coagulants in cases of CSU.3 However, conventional coagulation assays, such as activated partial thromboplastin time (APTT), that measure only the initiation time of clot formation do not reveal apparent abnormality in patients with CSU. Since many processes and proteins are involved in the coagulation, several global coagulation tests have been developed to assess the whole coagulation process. We previously revealed the increase of intrinsic coagulation potential in CSU patients, by one of the global coagulation tests, the APTT clot waveform analysis, and suggested that the activation of intrinsic coagulation factors may cause mast cell degranulation through the activation of protease-activating receptor-2 (PAR-2).4 However, an increased coagulation potential shown in the assay may not necessarily reflect the enhancement of intermediate coagulation factors, because the assay assesses the entire coagulation process from the beginning to fibrinogen-to-fibrin conversion. We, therefore, cannot exclude possible contributions of significantly elevated levels of fibrinogen, which may reflect chronic inflammation in CSU, to the hypercoagulable pattern of the assay. To clarify this, we further analyzed coagulation potentials in CSU, using calibrated automated thrombography (CAT). This approach measures the conversion of prothrombin to thrombin without fibrin generation, and thus eliminates the influence of fibrinogen levels (Fig. 1 inset).5 We also investigated the association between thrombin generation potentials and severities of CSU as well as the involvement of an autoimmune mechanism shown by autologous serum skin test (ASST), an in vivo test to demonstrate wheal-inducing factors in a patients serum and to assess autoreactivity.6

Tissue factor expression on the surface of monocytes from a patient with hereditary angioedema.

Hereditary angioedema (HAE) presents as severe angioedema, which is mostly due to the C1 inhibitor (C1‐INH) gene mutations. Environmental factors, minor trauma and oral contraceptives have been reported to induce angioedema attack, but the trigger may often be uncertain. Activated factor XII controlled by C1‐INH facilitates bradykinin generation and also regulates coagulation cascade, but the relationship between edema formation and coagulation is still unclear. We have described a 35‐year‐old female patient with HAE, presenting with frequent angioedema attacks in the absence of an apparent triggering factor. She showed higher levels of FDP and D‐dimer during angioedema than those in remission. In addition, tissue factor (TF), an initiator of the extrinsic coagulation cascade, was expressed on the surface of monocytes. It was significantly higher than that of monocytes from healthy controls and tends to further increase during attacks. The expression of TF on monocytes may play a role in the induction of angioedema attacks in HAE by activating the coagulation pathway in association with reduced functions of C1‐INH.