Objectives. Myositis-specific autoantibodies (MSAs) are useful tools in identifying clinically homogenous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have revealed that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study, we evaluated the frequencies and clinical associations of anti-NXP2 Ab in adult IIM patients.Methods. Clinical data and sera were collected from 507 adult Japanese patients with IIM (445 adult DM, and 62 adult PM). As disease controls, 11 with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis, and 124 with idiopathic pulmonary fibrosis were assessed. Sera were examined for anti-NXP2 Ab by immunoprecipitation and Western blotting using polyclonal anti-NXP2 Ab.Results. Seven patients (1.6%) with adult DM and 1 (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for 2 patients with JDM, no patients as disease controls were positive for this autoAb. Among 8 adult IIM patients, 3 had internal malignancies within 3 years of diagnosis of IIM. Another DM patient also had a metastatic cancer at the diagnosis. All of the carcinomas were advanced stage (stage IIIb-IV).Conclusions. While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.

There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, “the circadian clock,” remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ+ T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ+ T cells, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ+ T cells, establishing a mechanistic link between psoriasis and the circadian clock.

Pharmacologically resetting the molecular clock in mast cells or basophils to times when FcεRI signaling is reduced can inhibit IgE-mediated allergic reactions. The results suggest a new strategy for controlling IgE-mediated allergic diseases. Additionally, this study suggests a novel mechanism underlying the antiallergic actions of glucocorticoids that relies on the circadian clock, which might provide a novel insight into the pharmacology of this drug in allergic patients.

Background: It remains to be determined whether pemphigus vulgaris (PV), an autoimmune blistering disease, has a reduction and/or dysfunction of CD4⁺CD25^high regulatory T (Treg) cells. Objectives: To evaluate the frequency and phenotypes of Treg cells in blood of patients with PV. Methods: Peripheral blood mononuclear cells were prepared from PV patients as well as normal and disease control volunteers, and the frequency and phenotypes of Treg cells were determined by flow cytometry. CD4⁺CD25⁺ and CD4⁺CD25^– T cells isolated from peripheral blood mononuclear cells of PV patients and normal controls were subjected to real-time semiquantitative RT-PCR for the expression of Foxp3 gene. Results: The proportion of Treg cells in all PV patients was severely reduced, approximately ten times less than controls. These observations were further confirmed by both diminished gene and protein expression of Foxp3 in the CD4⁺CD25⁺ T cell population in PV patients. Conclusions: Numerical impairment of Treg cells may be involved in the pathogenesis of PV.

It remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several ‘clock genes’ including Clock drives daily rhythms in physiology. This study showed that allergen-induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time-of-day-dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone-marrow-derived basophils (BM basophils) generated from wild-type mice exhibited a time-of-day-dependent variation in IgE-mediated IL-4 and histamine production, which was not observed in BM basophils generated from Clock-mutated mice. Therefore, allergen-specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.