TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).

In the treatment of polymyositis and dermatomyositis (PM/DM), the complication of interstitial lung disease (ILD) is an important prognostic factor. It has been reported that autoantibodies against aminoacyl-tRNA synthetases (ARS) are strongly associated with ILD. The aim of this study is to examine the correlation between anti-ARS and the clinical course of ILD. We investigated 41 cases of PM/DM with ILD. The response of ILD to corticosteroids (CS) was determined according to the change in respiratory symptoms, image findings, and pulmonary function between, before and 2 months after the treatment. Anti-ARS (anti-Jo-1, PL-7, PL-12, EJ, OJ and KS) antibodies were screened with the RNA immunoprecipitation assay. In the stratification into ILD-preceding, simultaneous and myopathy-preceding types, anti-ARS antibodies were significantly frequent in the ILD-preceding type (p < 0.05). In the stratification into anti-ARS-positive and negative groups, the response of ILD to CS was significantly better in the positive group (p < 0.05). However, recurrence of ILD was significantly more frequent in the positive group (p < 0.01), and 2 year prognoses of pulmonary function (%VC and %DLCO) were not different between the two groups. In conclusion, screening of anti-ARS may be useful to predict late-onset myopathy in ILD-preceding patients and to predict the clinical course of ILD in PM/DM patients.

Nutritional status and immune function are closely related [1][2][3]. Food deprivation leads to impaired immune responses and an increase in the incidence of infectious disease, although the mechanism by which this occurs has yet to be elucidated. Adipose tissue preserves energy homeostasis through the storage of triglycerides. However, it has been found recently that a number of cytokine-like molecules, such as leptin [4], tumour necrosis factor-a (TNF-a) [5] and plasminogen activator inhibitor-1 (PAI-1) [6] are secreted from adipocytes, suggesting that adipose tissue may also play a role in the regulation of the immune and haematopoietic systems.Leptin is secreted specifically by adipocytes [4], and serum leptin levels are proportional to body mass index. However, the placenta [7] and stomach [8] provide additional sources of leptin. Leptin decreases food intake, increases energy expenditure and reduces body weight via leptin receptors within the ventromedial hypothalamus [9], where leptin functions to inhibit the production of neuropeptide Y which stimulates food intake [10]. The murine leptin and leptin-receptor mutants ob/ob and db/db, respectively, serve as animal models of obesity, and develop marked obesity and diabetes due to deficiencies in leptin signalling [11]. In contrast, leptin transgenic mice with elevated plasma leptin concentrations lack brown or white adipose tissue, show reduced food intake, and are markedly lean in comparison with non-transgenic littermates [12].The leptin receptor is expressed in peripheral tissues such as the kidney, lung and adrenal gland [13,14], and several in vitro studies have demonstrated that leptin acts directly on the leptin receptor [15,16]. There are at least five splice variants of the leptin receptor Ob-Ra-Ob-Re, and one of these five variants, Ob-Rb, possesses a long intracellular domain demonstrating homology with gp130, a subunit of the IL-6 family of cytokine receptors [17]. On the other hand, Ob-Ra, one of the shortest forms of the leptin receptor, lacks the STAT3 activation domain and is not considered essential for signal transduction [18].Recent studies have revealed that Ob-Rb is expressed in fetal liver haematopoietic precursor cells, bone marrow and peripheral T cells [14,19]. In adult human bone marrow, both CD34 positive and negative cells express leptin receptor. These findings suggest the possibility that leptin not only regulates body weight, but also modulates the immune system. Indeed, leptin increases the proliferation of haematopoietic stem cell populations at the multilineage progenitor level [18], enhances alloproliferative mixed-lymphocyte reactions, and reverses cellular immune function in fasted mice [20]. In addition, leptin might act as a growth factor for both myeloid leukaemic cells [21] and lung cancer cells [22]. In addition, human white blood cell counts are correlated with body mass index and serum leptin levels [23]. Moreover, diminished cell-mediated immunity and decreased lymphocyte counts have been reported in ob/ob and db...

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

Objective. To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE).Methods. The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. Systemic lupus erythematosus (SLE) is a chronic, remitting and relapsing, multisystem autoimmune disease that predominantly affects women. Neuropsychiatric SLE (NPSLE) involving the central nervous system (CNS; central NPSLE) is a severe, life-threatening manifestation. The overall prevalence of NPSLE varied from 14% to 75% in a representative selection of studies using the American College of Rheumatology (ACR) nomenclature (1). In fact, NPSLE may affect mortality in SLE and is associated with a significant negative impact on a patient's quality of life. However, 41% of all CNS manifestations in patients with SLE may be attributed to factors other than lupus (2).Although the pathophysiology of most NPSLE cases is not well determined, a particular subset of