Recent advances in the treatment strategy for AAV improved outcomes with intensive GC tapering.

OBJECTIVE: To evaluate trends in results of care and management for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). METHODS: We employed multicenter cohort data collected during 2011-2021, recruiting 43 patients with granulomatosis with polyangiitis (GPA) and 91 with microscopic polyangiitis (MPA). According to the median registration date of September 2015, patients have split into two groups: an early group and a late group (both of them, n = 67). To prevent bias, a propensity score according to numerous baseline characteristics variables was calculated; 50 matching members of each group were statistically extracted. Their treatments and clinical outcomes were examined at 6, 12, and 24 months after initial remission therapy. RESULTS: Statistics demonstrated that the baseline characteristics were similar. The late group used rituximab (RTX) more often for both remission induction and maintenance therapy, compared with the early group. The mean daily PSL doses of the late group were significantly lower than those of early group at each time point. The late group discontinued PSL 14.0% at 12 months and 23.3% at 24 months. Despite their intensive glucocorticoids (GC) tapering, the remission rates and the relapse rates were significantly fairer in the late group. The Vasculitis Damage Index (VDI) and VDI due to GC at each time point were lower in the late group, and those differences had become wider over time. CONCLUSION: Recent developments in AAV treatment have allowed efficient remission and prevention of relapses, which in turn enabled extensive GC tapering causing fewer sequelae.

Anaplastic Lymphoma Kinase Overexpression Is Associated with Aggressive Phenotypic Characteristics of Ovarian High-Grade Serous Carcinoma.

Deregulated full-length anaplastic lymphoma kinase (ALK) overexpression has been found in some primary solid tumors, but little is known about its role in ovarian high-grade serous carcinoma (HGSC). The current study focused on the functional roles of ALK in HGSC. Cytoplasmic ALK immunoreactivity without chromosomal rearrangement and gene mutations was significantly higher in HGSC compared with non-HGSC-type ovarian carcinomas, and was significantly associated with several unfavorable clinicopathologic factors and poor prognosis. HGSC cell lines stably overexpressing ALK exhibited increased cell proliferation, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown cells. Expression of the nervous system-associated gene, ELAVL3, and the corresponding protein (commonly known as HuC) was significantly increased in cells overexpressing ALK. Expression of SRY-box transcription factor (Sox)2 and Sox3 (genes associated with the neural progenitor population) increased in ALK-overexpressing but not ALK-knockdown cells. Furthermore, overexpression of Sox2 or Sox3 enhanced both ALK and ELAVL3 promoter activities, suggesting the existence of ALK/Sox/HuC signaling loops. Finally, ALK overexpression was attributed to increased expression of neuroendocrine markers, including synaptophysin, CD56, and B-cell lymphoma 2, in HGSC tissues. These findings suggest that overexpression of full-length ALK may influence the biological behavior of HGSC through cooperation with ELAVL3 and Sox factors, leading to the establishment and maintenance of the aggressive phenotypic characteristics of HGSC.

The Association of Airway Comorbidities With the Clinical Phenotypes and Outcomes of Patients With Antineutrophil Cytoplasmic Autoantibody-associated Vasculitis.

OBJECTIVE: We investigated the association of airway comorbidities with the clinical phenotypes and outcomes of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-positive ANCA-associated vasculitis (AAV). METHODS: An AAV patient multicenter cohort trial was established in 13 hospitals in western Japan between 2012 and 2018. We examined 143 of the new-onset MPO-ANCA-positive AAV patients. Their clinical characteristics and comorbidities at disease onset were compared based on clinical phenotypes. Multivariate analysis was performed to identify factors predictive of remission and death. RESULTS: Twenty-seven cases with granulomatosis with polyangiitis (GPA), 10 with eosinophilic GPA (EGPA), 81 with microscopic polyangiitis (MPA), and 25 with unclassified AAV were identified. The average age of MPO-ANCA-positive patients was 71.4 years. Comorbidity (87.4%) and airway comorbidity (70.6%) were frequently observed in these patients. Examination of the clinical phenotypes revealed that the cases of GPA were frequently accompanied by infectious airway comorbidity (upper airway disease, bronchiectasis, pulmonary infections), and most of the cases of MPA and unclassified AAV were accompanied by fibrotic interstitial lung disease (fILD) or emphysema. Among MPO-ANCA-positive patients, infectious airway comorbidity was predictive of both remission (HR 1.58, P = 0.03) and mortality (HR 2.64, P = 0.04), and fILD was predictive of mortality (HR 7.55, P = 0.008). The combination of infectious airway comorbidities and fILD caused the worst survival outcomes in patients. CONCLUSION: MPO-ANCA-positive AAV was frequently accompanied by airway comorbidities. In addition to fILD, infectious airway comorbidities were closely associated with those clinical phenotypes and outcomes.

Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan.

OBJECTIVES: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. RESULTS: We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. CONCLUSION: RTX maintenance therapy could be effective and safe in Japanese GPA patients.

[A Patient Surviving More Than Five Years Due to the Effect of Sequential Alternating Chemotherapy Administered to Metachronous Overlapping Cancer of Multiple Myeloma and Stageâ £ EGFR Positive Non-Small Cell Lung Cancer].

A woman in her late 50s visited our department because an abnormal shadow of her right lung was seen on her chest radiographs. She was diagnosed with Stage ⅠA primary lung adenocarcinoma with EGFR exon 19 deletion mutation by performing thoracoscopic middle lobe resection and lymph node dissection. After 1 and a half years, the lung metastasis recurred and she received gefitinib(GEF)monotherapy for 9 months and withdrew because of the sustained complete response(CR). Three years and 7 months after the first visit, she was diagnosed as having complication of revised international staging system(R-ISS)Ⅱ multiple myeloma with anemia, retinal vein occlusion, and M proteinemia. It was decided that treatment for myeloma should be given priority and hence, Bd, high dose chemotherapy with auto-peripheral blood stem cell transplantation(aPBSCT), Ld, ELd and Pd therapy were performed sequentially until progressive disease(PD)and survival benefit were evident. As lung metastasis of adenocarcinoma also progressed, myeloma treatment was terminated, GEF was administered intermittently and consequently, shrinkage of the lung metastasis was confirmed. Depending on sequential alternating chemotherapy for both malignancies, a relatively long survival time of 5.4 years from the initiation of treatment for myeloma and 7.5 years from the recurrence of lung adenocarcinoma was achieved.

[A Case of Synchronous Diffuse Large B-Cell Lymphoma of the Right Breast and Invasive Ductal Carcinoma of the Left Breast].

A woman in her early 60s noticed bilateral breast masses and visited a different hospital. Core needle biopsy showed diffuse large B-cell lymphoma of the right breast and invasive ductal carcinoma of the left breast. After referral to our department, PET-CT was performed. Compared with mild fluorodeoxyglucose accumulation in left breast cancer(BC), highly accumulated lesions were found on the right breast, left anterior chest wall, nasopharynx, and tonsil. The right breast lesion was the largest with a diameter of 30mm and was considered the primary lesion of malignant lymphoma(ML). The ML was classified as stage Ⅳ, pathologically proven with erythema of the left breast and nasopharynx. Three courses of R-CHOP were performed. However, due to suspicion of heart failure, chemotherapy was changed to R-CEOP(non-anthracycline-containing regimen)and 3 courses were additionally performed. The therapeutic effect of R-Chemo for ML was CR. Left BC showed a tendency of shrinkage. After intrathecal administration of anticancer drugs to prevent infiltration of ML into the central nervous system and preoperative endocrine therapy with aromatase inhibitor, left lumpectomy and sentinel lymph node biopsy were performed. BC was classified as clinical stage ⅠA and had an estrogen receptor score of 3b. Postoperative whole breast radiotherapy was completed, and the planned internal use of exemestane was more than 5 years. With multidisciplinary therapy, 3.5 years had passed since the initial treatment without recurrence.

Prevalence of oral health-related conditions that could trigger accidents for patients with moderate-to-severe dementia.

OBJECTIVE: This study was performed to determine the prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents in hospitalised patients with moderate-severe dementia. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Dementia patients may not recognise risks in the mouth, such as tooth mobility or ill-fitting dental prostheses and/or dentures. In addition to the risk of choking, injury by sharp edges of collapsed teeth or prosthodontics could pose risks. However, many previous publications were limited to case reports or series. MATERIALS AND METHODS: Ninety-two consecutive hospitalised dementia patients (M: 52, F: 40, median age: 82.5 years, range: 62-99 years, from 2011 to 2014), referred for dentistry for dysphagia rehabilitation, were enrolled in this study. Participants referred for dental treatment with dental problems detected by ward staff were excluded. All participants had a Global Clinical Dementia Rating Score >2. Their dental records were evaluated retrospectively for issues that may cause incidents and/or accidents. RESULTS: Problems in the mouth, for example tooth stumps, dental caries, and ill-fitting dentures, were detected in 51.1% of participants (47/92). Furthermore, 23.9% (22/92) showed risk factors that could lead to incidents and/or accidents, for example falling out of teeth and/or prosthodontics or injury by sharp edges of teeth and/or prosthodontics. CONCLUSIONS: Hospitalised moderate-severe dementia patients had a high prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents.

Cooperation of Sox4 with ß-catenin/p300 complex in transcriptional regulation of the Slug gene during divergent sarcomatous differentiation in uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) represents a true example of cancer associated with epithelial-mesenchymal transition (EMT), which exhibits cancer stem cell (CSC)-like traits. Both Sox and ß-catenin signal transductions play key roles in the regulation of EMT/CSC properties, but little is known about their involvement in UCS tumorigenesis. Herein, we focused on the functional roles of the Sox/ß-catenin pathway in UCSs. METHODS: EMT/CSC tests and transfection experiments were carried out using three endometrial carcinoma (Em Ca) cell lines. Immunohistochemical investigation was also applied for a total of 32 UCSs. RESULTS: Em Ca cells cultured in STK2, a serum-free medium for mesenchymal stem cells, underwent changes in morphology toward an EMT appearance through downregulation of E-cadherin, along with upregulation of Slug, known as a target gene of ß-catenin. The cells also showed CSC properties with an increase in the aldehyde dehydrogenase (ALDH) 1(high) activity population and spheroid formation, as well as upregulation of Sox4, Sox7, and Sox9. Of these Sox factors, overexpression of Sox4 dramatically led to transactivation of the Slug promoter, and the effects were further enhanced by cotransfection of Sox7 or Sox9. Sox4 was also able to promote ß-catenin-mediated transcription of the Slug gene through formation of transcriptional complexes with ß-catenin and p300, independent of TCF4 status. In clinical samples, both nuclear ß-catenin and Slug scores were significantly higher in the sarcomatous elements as compared to carcinomatous components in UCSs, and were positively correlated with Sox4, Sox7, and Sox9 scores. CONCLUSIONS: These findings suggested that Sox4, as well as Sox7 and Sox9, may contribute to regulation of EMT/CSC properties to promote development of sarcomatous components in UCSs through transcriptional regulation of the Slug gene by cooperating with the ß-catenin/p300 signal pathway.

Frequent ß-catenin gene mutations in atypical polypoid adenomyoma of the uterus.

Atypical polypoid adenomyoma (APA) is an uncommon polypoid lesion of the uterus. To clarify the mechanism of its histogenesis, we examined the functional role of ß-catenin, with reference to expression of p21(waf1), cyclin D1, cyclin E, CD10, and α-smooth muscle actin (SMA), as well as cell proliferation, in 7 lesions. In the epithelial components, expression of nuclear ß-catenin, p21(waf1), and cyclin D1 was increased in a stepwise fashion from normal tissue through complex atypical hyperplasia and adenomyoma to APA lesions, particularly in squamous morular areas, whereas cell proliferation, as well as cyclin E expression, was significantly decreased in the latter. Similar findings were evident in the stromal lesions, with the exception of a case of nuclear ß-catenin. In addition, coexpression of CD10 and α-SMA markers was observed in the stromal components in 3 APA cases, in line with the results of normal secretory endometrial and adenomyoma samples, suggesting that cells progress to myofibromatous cells in response to differentiation-promoting events. Finally, ß-catenin gene (CTNNB1) mutations were detected in all APA cases, the single nucleotide substitutions being in the epithelial but not the stromal components. These findings suggest that activation of ß-catenin signaling, probably secondary to the gene abnormalities, plays an important role in the formation of the complex epithelial architecture in APAs, leading to inhibition of cell proliferation through overexpression of p21(waf1). In contrast, changes in the stromal cell phenotype may occur through a shift from CD10 to α-SMA immunopositivity, independent of CTNNB1 status.

Transcriptional upregulation of HIF-1α by NF-κB/p65 and its associations with ß-catenin/p300 complexes in endometrial carcinoma cells.

The hypoxia-inducible factor (HIF)-1α, which has a major role in cell adaptation to hypoxia, is mainly regulated at post-translational levels. Recently, HIF-1α mRNA was also shown to be upregulated by several signal pathways under normoxic conditions. Here we focused on relationships of HIF-1α with NF-κB and ß-catenin signaling in endometrial carcinomas (Em Cas). Long-term exposure of Ishikawa cells to cobalt chloride (CoCl2), which is known to mimic the effect of hypoxia, caused a decrease in the growth, along with increased HIF-1α protein but not mRNA expression. In contrast, short-term exposure resulted in a rapid and transient increase in HIF-1α mRNA expression along with stabilization of nuclear NF-κB/p65 (p65). Transfection of p65 increased HIF-1α expression through activation of the promoter, whereas overexpression of HIF-1α also activated NF-κB-dependent transcription, indicating the existence of a positive feedback loop. In addition, HIF-1α was indirectly associated with nuclear ß-catenin through interactions with p300, leading to slight enhancement of both HIF-1α- and ß-catenin-mediated transcriptional activity. In clinical samples, biphasic upregulation of HIF-1α expression was observed in normal endometrial glandular components during the menstrual cycle, with the labeling indices showing significantly higher values in the early secretory stage. Significantly higher values for phosphorylated p65 and nuclear ß-catenin were also observed in HIF-1α-positive than -negative lesions of Em Cas, in contrast to significantly lower Ki-67 status. These data therefore suggest that transcriptional associations with HIF-1α and NF-κB, as well as ß-catenin/p300 complexes, may contribute to modulation of changes in tumor cell kinetics in response to a hypoxic condition in Em Cas.

[BCMA and autoantibody-producing RP105 B cells; possible new targets of B cell therapy in systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with multiple organ disorders. Although the prognosis of SLE has been recently improved, corticosteroid and immunosuppressive agents are still main treatment used in medical practice. Refractory disease and complications by the conventional drugs still remain. RP105 (CD180) is one of the toll-like receptor associated molecules. The molecule is expressed on mature B cells. Significantly increased population of RP105-negative [RP105(-)] B cells is found in SLE. RP105(-) B cells belong to highly activated and differentiated late B cells and produce autoantibodies including anti-dsDNA antibodies. RP105(-) B cells are further divided into at least 5 subsets that include novel human B cell subsets. In active SLE, subset 1 (activated B cells) and 3 (early-plasmablasts) are significantly increased compared to inactive SLE patients. Especially, subset 3 RP105(-) B cells may play an important role in pathophysiology of SLE. RP105(-) B cells from active SLE patients express preferentially BCMA (B-cell maturation antigen) compared to BAFF-R (B-cell activating factor-receptor) than normal subjects and other autoimmune diseases. In SLE, it is suggested that BAFF/APRIL (a proliferation-inducing ligand) maintain chronic activation and survival of RP105(-) B cells. The increased RP105(-) B cells may reflect the breaking of tolerance checkpoint for autoreactive B cells and finally affect autoimmunity in SLE. For the B cell therapy, especially targeting of autoantibody-producing B cells, including subset 3 of RP105(-) B cells, BCMA and RP105(-) B cell itself may be an ideal target.

Phenotyping of P105-negative B cell subsets in patients with systemic lupus erythematosus.

This study aimed to investigate phenotype of RP105(-) B cell subsets in patients with systemic lupus erythematosus (SLE). Flow cytometry was used for phenotyping RP105-negaive B cell subsets. Based on CD19, RP105, and CD138 expression, RP105(-) B cells consist of at least 5 subsets of late B cells, including CD19(+)RP105(int), CD19(+) RP105(-), CD19(low) RP105(-) CD138(-), CD19(low) RP105(-)CD138(int), and CD19(low) RP105(-) CD138(++) B cells. Especially, CD19(+)RP105(int) and CD19(low) RP105(-)CD138(int) B cells are significantly larger than other RP105(-) B cell subsets in SLE. By comparison of RP105(-) B cell subsets between patients with SLE and normal subjects, these subsets were detectable even in normal subjects, but the percentages of RP105(-) B cell subsets were significantly larger in SLE. The phenotypic analysis of RP105(-) B cell subsets suggests dysregulation of later B cell subsets in SLE and may provide new insights into understanding regulation of B cells in human SLE.

Therapeutic response of patients with adult Still's disease to biologic agents: multicenter results in Japan.

OBJECTIVE: The efficacy of biologics in treating adult Still's disease (ASD) is suggested, but the information is still lacking and the validation is insufficient. To determine the efficacy of several biologic agents in refractory ASD in Japan, a multicenter survey was performed. METHOD: Clinical data on 16 ASD patients who had been treated with at least 1 of the biological agents (total 24 occasions) were collected retrospectively. RESULTS: Infliximab was used in 9 cases, etanercept in 4, and tocilizumab in 11. Half of the patients that had been treated initially with infliximab or etanercept were changed to another biologics. Tocilizumab was effective in cases switched from another 2 drugs. Tocilizumab showed efficacy in treating both systemic and arthritic symptoms and showed apparent steroid-sparing effect and the highest continuation rate. CONCLUSION: Tocilizumab may be a promising biologic agent in refractory ASD.

[Case of microscopic polyangiitis and giant cell arteritis after influenza vaccination].

We report a case of microscopic polyangiitis (mPA) and giant cell arteritis (GCA) (polyangiitis overlap syndrome) after influenza vaccination. A 67-year-old female with chronic kidney disease, who had been observed by a physician, presented fever and headache after immunization of influenza vaccine. She was diagnosed as having with mPA and GCA based on symptoms, worsening of renal function, biopsy of temporal artery (giant cell arteritis) and skin (microscopic polyangiitis), pulmonary involvement and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). She was treated with prednisolone (PSL) and the symptoms were improved. However, two months later she was presented with general physical weariness. She was diagnosed as having with pneumocystis pneumonia, cytomegalovirus infection and cryptococcosis. Despite intensive treatment, she was died and autopsy was performed. The present case suggests that the influenza vaccination may cause different types of vasculitis, mPA and GCA, through the common mechanism in pathophysiology. This patient is also the first case of mPA and GCA proven by histological examination.

Interferon regulatory factor 5 is critical for the development of lupus in MRL/lpr mice.

OBJECTIVE: Interferon regulatory factor 5 (IRF-5) is a transcription factor that mediates intracellular signals activated by engagement of Toll-like receptors (TLRs). IRF5 polymorphisms are associated with an increased or decreased risk of systemic lupus erythematosus (SLE) in various human populations, but the precise role of IRF5 in SLE development is not fully understood. This study was undertaken to examine the role of IRF5 in the development of murine lupus. METHODS: We crossed gene-targeted IRF5-deficient (IRF5(-/-) ) mice with MRL/MpJ-lpr/lpr (MRL/lpr) mice and examined the progeny for survival, glomerulonephritis, autoantibody levels, immune system cell populations, and dendritic cell function. RESULTS: IRF5(-/-) MRL/lpr mice survived longer than control IRF5(+/+) MRL/lpr mice and displayed only very mild glomerulonephritis. Autoantibodies to SLE-related nuclear antigens were lower in IRF5(-/-) MRL/lpr mouse serum, and numbers of activated CD4+ T cells were reduced in the spleen. Splenic DCs from IRF5(-/-) MRL/lpr mice produced lower levels of inflammatory cytokines when treated in vitro with TLR-7 or TLR-9 ligands or immune complexes. Interferon-α production in response to CpG was also decreased. CONCLUSION: Our results show that IRF5 is a crucial driver of lupus development in mice, and indicate that IRF5 may be an attractive new target for therapeutic intervention to control disease in SLE patients.

Functional disturbance of the stress-adaptation system in patients with scleroderma.

There have been several reports indicating the association between recent stress experiences and the onset or the exacerbation of rheumatic diseases, although few such reports exist in patients with scleroderma (SSc). The present study was performed to elucidate whether there were any functional disturbances in the neuro-endocrine-immune system as a homeostatic system upon stress in SSc patients. Various serum levels of stress-related hormones and cytokines were examined before and after a mental calculation stress test, and a basal questionnaire study of sense of coherence (SOC, which is related to the ability to cope with stress), recent stress experiences, and quality of life (QOL) was performed in 17 SSc patients and in 38 healthy volunteers. Physical QOL state was impaired in patients, but there were no differences in recent stress experiences and SOC scores between patients and controls. Basal serum cortisol levels were similar in patients and controls, but increased levels of proinflammatory cytokine and noradrenalin were seen in SSc patients. Characteristically, contrary to the control group, whose cortisol levels increased significantly following the mental calculation stress test, no significant increase was observed in the patients when post-test cortisol levels were compared to pre-test levels, suggesting a defect in the normal cortisol response upon stress in SSc patients. The present results suggest that there may be impaired function of the neuro-endocrine-immune system upon stress in SSc patients.

[A case of cutaneous Mycobacterium nonchromogenicum infection suggesting sarcoidosis association].

A 67-year-old man clinically diagnosed a year earlier with sarcoidosis based on low-grade fever, lymphadenopathy, trunk skin rash, and histopathological skin tests was admitted for newly developing subcutaneous nodules on the trunk and arms and fever of 38 degrees C. Although initially suspected of recurrent sarcoidosis, he was diagnosed with Mycobacterium chromogenicum infection isolated from skin lesion culture. Combined clarithromycin of 800 mg/day, ethambutol of 750 mg/day, and embiomycin of 0.5 g/day was started, after which fever declined and WBC count and CRP decreased to normal in a week. One month later, skin lesions had disappeared. This case is interesting considering the association of nontuberculous mycobacterial infection with sarcoidosis.

Autoantibody-producing RP105(-) B cells, from patients with systemic lupus erythematosus, showed more preferential expression of BCMA compared with BAFF-R than normal subjects.

OBJECTIVE: B cells lacking RP105 produce autoantibodies in patients with SLE. Expression of B-cell activating factor (BAFF) binding receptors (BBRs) and survival of RP105(-) B cells from SLE patients were examined. METHODS: Detection of difference of gene expression between RP105(-) and RP105(+) B cells was done by DNA microarrays. Surface expression was confirmed by flow cytometry. The contribution of BAFF, a proliferation-inducing ligand (APRIL) and monomers/trimers of sCD40L to survival of RP105(-) and RP105(+) B cells was examined. RESULTS: Gene expression of B-cell maturation antigen (BCMA) was different among BBRs in RP105(-) and RP105(+) B cells in SLE. Preferential expression of BCMA on RP105(-) B cells was confirmed compared with RP105(+) B cells by flow cytometry, although BAFF receptor (BAFF-R) expression on RP105(-) B cells was significantly lower. Additionally, relative ratios of BCMA/BAFF-R expression on RP105(-) B cells were increased significantly in SLE patients compared with normal subjects. Stimulation by sCD40L decreased the number of surviving RP105(-) and RP105(+) B cells in vitro. RP105(+) B cells were not rescued from sCD40L-induced cell death by BAFF and/or APRIL. In contrast, either BAFF or APRIL maintained the survival of RP105(-) B cells due to avoidance of cell death. Activated RP105(-) B cells reduced BAFF-R and increased BCMA levels. CONCLUSIONS: RP105(-) B cells from SLE patients showed more preferential expression of BCMA compared with BAFF-R than normal subjects, and were possibly regulated by BAFF/APRIL. Our results provide a new insight of BCMA and their ligands in B cells from SLE patients.

Cyclosporin A treatment for Japanese patients with severe adult-onset Still's disease.

For over 10 years there have been no clinical studies about adult-onset Still's disease (AOSD) in Japan. We aimed to investigate recent clinical features and treatment of AOSD and to evaluate the efficacy of cyclosporin A (CyA) in the treatment of AOSD. The data from 34 patients with AOSD who were admitted to our hospital between 1994 and 2007 were analyzed retrospectively. Of several immunosuppressive agents, the efficacy of CyA given to seven patients was precisely evaluated. Clinical features observed in this study did not differ from those in our previous study, and serum ferritin levels were elevated in all the patients. Among immunosuppressive agents CyA, used concomitantly with corticosteroids (CS) for seven patients with severe AOSD, proved to be very effective. The disease was led to remission promptly by CyA in six patients, and all the patients except one experienced no recurrence. These results suggest that CyA can be one of the potent candidates to be used next to CS for patients with AOSD that is resistant to CS.