A nationwide analysis of renal and patient outcomes for adults with lupus nephritis in Japan.

BACKGROUND: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. METHODS: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. RESULTS: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. CONCLUSION: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.

SIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen.

In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4+ cDCs as well as that of Pdpn+ FRCs and T cells in the adult mouse spleen. Such ablation also impaired the survival of FRCs as well as the production by CD4+ cDCs of tumor necrosis factor receptor (TNFR) ligands, including TNF-α, which was shown to promote the proliferation and survival of Pdpn+ FRCs. CD4+ cDCs thus regulate the steady-state homeostasis of FRCs in the adult spleen via the production of TNFR ligands, with the CD47-SIRPα interaction in cDCs likely being indispensable for such regulation.

TGF-ß1 alters DNA methylation levels in promoter and enhancer regions of the WT1 gene in human podocytes.

AIM: Wilms' tumour 1 (WT1) is essential for normal podocyte function. Previous reports have demonstrated that the WT1 promoter is often methylated in cancers, leading to transcriptional silencing. Transforming growth factor-ß1 (TGF-ß1) is reported to down-regulate WT1 expression in podocytes. Based on the hypothesis that epigenetic modification plays a role in this process, we examined whether TGF-ß1 affects the methylation status of WT1 regulatory regions. METHODS: Conditional immortalized human podocytes were treated with TGF-ß1. A human renal proximal tubular epithelial cell line (HK2), which does not express WT1, was used as a control. The degree of DNA methylation of the WT1 promoter, 5' enhancer, intron 3 enhancer and 3' enhancer was determined using quantitative methylation-specific PCR, bisulfite sequencing and pyrosequencing. RESULTS: Both WT1 mRNA and protein expression were reduced by long-term treatment with TGF-ß1. The WT1 promoter was hypomethylated, and the 5' enhancer and intron 3 enhancer were substantially methylated in untreated podocytes. In contrast, in HK2 cells, the WT1 promoter was strongly methylated, and the 5' enhancer and intron 3 enhancer were less methylated than in untreated podocytes. TGF-ß1 tended to increase WT1 promoter methylation, tended to decrease 5' enhancer methylation and significantly decreased intron 3 enhancer methylation in podocytes. Methylation levels of the 3' enhancer did not differ among untreated cells, TGF-ß1-treated podocytes or HK2 cells. CONCLUSION: Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-ß1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-ß1, which could contribute to podocyte injury.

Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed AML.

We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty-nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition. Notably, patients with ACA acquisition showed a significantly lower second complete remission rate compared with those without ACA acquisition (20.0% vs 72.5%, respectively, P < .001). Furthermore, the 3-year overall survival rates after the first relapse were significantly different between patients with and without ACA acquisition (8.5% vs 36.8%, respectively, P < .001). This prognostic significance was confirmed with multivariate analysis. The hazard ratio of ACA acquisition was similar or higher than reported prognostic factors for relapsed AML patients. These findings suggested that clonal evolution detected with conventional cytogenetic analysis at the first relapse induces severe chemo-refractory characteristics in AML cells and should be considered as a potent prognostic factor when evaluating accurate prognosis in relapsed AML patients.

A Rare Case of Chronic Active Epstein-Barr Virus (EBV) Infection Accompanied by the Infiltration of EBV-infected CD8+ T Cells into the Muscle.

We describe a rare case of chronic active Epstein-Barr virus (CAEBV) infection, with infiltration of the skeletal muscle. A 19-year-old woman with swollen cervical lymph nodes and a fever was referred to our hospital. Swelling of the trapezium muscle and elevation of creatinine kinase level were observed. Biopsy results of the brachialis muscle revealed infiltration of Epstein-Barr virus (EBV)-encoded RNA-positive CD8 T lymphocytes. The EBV virus load in the peripheral blood was high, and EBV monoclonality was determined by Southern blot analysis. Owing to the rarity of CAEBV with skeletal muscle infiltration, this case alerts physicians to the potential diagnostic pitfalls of CAEBV.

Involvement of infiltrating macrophage-derived activin A in the progression of renal damage in MRL-lpr mice.

Lupus nephritis is a life-threatening complication of systemic lupus erythematosus (SLE). Various growth factors, cytokines, and chemokines are implicated in the development of SLE. However, the pathophysiological processes involved in the development of lupus nephritis still remain unclear. In this study, we examined the involvement of activin A, a member of the transforming growth factor ß (TGF-ß) superfamily, in the progression of renal damage in lupus-prone MRL-lpr mice. Activin A was not expressed in the kidneys of control MRL-MpJ mice but was detectable in perivascular infiltrating cluster of differentiation 68 (CD68)-positive cells in the kidneys of MRL-lpr mice. Urinary activin A, which was also absent in MRL-MpJ mice, was detectable in MRL-lpr mice from 16 wk onward. Urinary activin A levels were significantly correlated with the number of perivascular inflammatory cell layers, the number of crescentic glomeruli, and the percentage of Elastica van Gieson (EVG)-positive fibrotic areas, but not with urinary protein levels or serum activin A. When activin action was blocked in vivo by the intraperitoneal administration of an activin antagonist, follistatin, the number of crescentic glomeruli, percentage of EVG-positive fibrotic areas, CD68-positive cell infiltration, and proteinuria were significantly reduced in a dose-dependent manner. These data suggest that infiltrating macrophage-derived activin A is involved in the progression of renal damage in MRL-lpr mice.

Overexpression of B-cell lymphoma 6 alters gene expression profile in a myeloma cell line and is associated with decreased DNA damage response.

B-cell lymphoma 6 (BCL6) attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage. In contrast, transcription of known targets of BCL6 in GC B cells was not affected, suggesting a cell type-specific function of BCL6. To further investigate the effects of BCL6 overexpression on the MM cell line, we undertook mRNA sequence analysis and found an upregulation in the genomic mutator activation-induced cytidine deaminase (AID) with alteration in the gene expression profile, which is suggestive of de-differentiation from plasma cells. Moreover, interleukin-6 exposure to KMS12PE led to upregulation of BCL6 and AID, downregulation of ATM, and attenuation of DDR, which were consistent with the effects of BCL6 overexpression in this MM cell line. Taken together, these results indicated that overexpression of BCL6 alters gene expression profile and confers decreased DDR in MM cells. This phenotypic change could be reproduced by interleukin-6 stimulation, suggesting an important role of external stimuli in inducing genomic instability, which is a hallmark of MM cells.

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism.

Autoimmune hemophilia-like disease (hemorrhaphilia) due to anti-factor XIII (FXIII) antibodies (AH13) is a very rare, life-threatening bleeding disorder. A 77-year-old woman developed macrohematuria and a right renal pelvic hematoma. The coagulation times were not prolonged, but FXIII activity and antigen levels were severely and moderately reduced to 9 and 29% of normal values, respectively. Accordingly, the FXIII-specific activity turned out to be low. FXIII inhibitor and anti-FXIII-A subunit autoantibodies were detected by a 1:1 crossmixing test and immunoblot and immunochromatographic assays. She was therefore diagnosed with "definite AH13" and treated with plasma-derived FXIII concentrates to arrest the hemorrhage. In addition to a highly compressed inferior vena cava by a huge renal pelvic hematoma, deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) were identified by systemic computed tomography. The patient was immediately started on anticoagulation therapy with low-dose heparin. Emboli disappeared quickly, probably because under-crosslinked thrombi caused by severe FXIII deficiency are vulnerable to fibrinolysis. After about 1.5 years, anti-FXIII-A subunit autoantibodies still remained despite the use of rituximab, steroid pulse therapy, oral prednisolone, and oral cyclophosphamide treatments. In conclusion, an extremely rare AH13 case complicated by DVT and PE was successfully managed by balancing anticoagulation therapy with hemostatic therapy.

Clinical and histological features of lupus nephritis in Japan: A cross-sectional analysis of the Japan Renal Biopsy Registry (J-RBR).

AIM: The clinical and histological features of lupus nephritis (LN) are highly variable, depending on race and ethnicity. The Japan Renal Biopsy Registry (J-RBR) is a nationwide registry of renal biopsies. Here, we report a cross-sectional analysis of Japanese LN using the J-RBR database. METHODS: Out of 18 463 patients registered in the J-RBR, 331 LN patients, who received renal biopsy for the first time, were extracted and their clinical features were analyzed according to the ISN/RPS 2003 classification. RESULTS: The median age of the 331 LN patients was 37 years (women, 81.3%). The frequencies of each of the ISN/RPS Classes were as follows: I, 1.2%; II, 7.9%; III (±V), 25.1%; IV-S (±V), 13.0%; IV-G (±V), 31.1%; V, 20.8%; and VI, 0.9%. The level of proteinuria and the prevalence of nephrotic syndrome were highest for Class IV-G (±V). When Classes I, II, and VI were excluded from the analysis, Class IV-G (±V) was significantly associated with a lower eGFR and severer haematuria than the other classes. CONCLUSION: This nationwide study revealed that Class IV-G (±V) was the most prevalent form of LN in Japan and was associated with a severe clinical renal presentation.

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.

Late-onset neutropenia after rituximab therapy in patients with autoimmune thrombotic and hemostatic disorders: a single center analysis.

Autoimmune thrombotic and hemostatic disorders, caused by autoantibodies against various factors regulating thrombosis and hemostasis, are rare. Rituximab (RTX) is on occasion used for treating these disorders. Late-onset neutropenia (LON) has been described as a side effect of RTX treatment for patients with hemato-oncological and/or rheumatological diseases but not for those with autoimmune thrombotic and hemostatic disorders. Eleven patients with autoimmune thrombotic and hemostatic disorders received RTX in our institution. Four of these 11 cases (36.4%) developed LON after a median 72.6 days of RTX administration (range 43-122). Three cases required G-CSF, but no severe infections developed.

Acquired thrombotic thrombocytopenic purpura with a smoldering clinical course.

Acquired thrombotic thrombocytopenic purpura (aTTP) is caused by a deficiency of ADAMTS13 activity due to neutralizing auto-autoantibodies (inhibitors) against ADAMTS13. Patients with aTTP show a rapid and fatal clinical course, unless an effective therapeutic intervention such as plasma exchange therapy (PEX) is performed. There is, however, a small population of patients who show a smoldering clinical course, for which no effective treatment strategy has yet been established. We herein report a 77-year-old man, who had repeated episodes of cerebral infarction and persistent thrombocytopenia over several months, but was not correctly diagnosed as having aTTP at a local hospital. However, sudden progression to an unconsciousness state together with thrombocytopenia prompted his physician to make a clinical diagnosis of aTTP, and the patient was then referred to our hospital, where the diagnosis of aTTP was confirmed by analyzing ADAMTS13. An improvement of his clinical signs was achieved with PEX and steroid therapy, but the latter had to be discontinued due to the development of grade 3 liver dysfunction. Despite discontinuation of steroid therapy, his clinical condition remained stable, but with a persistently low level of ADAMTS13 activity associated with the presence of low-titer inhibitors. Our experience may raise awareness of the diagnosis and treatment of aTTP with a smoldering clinical course.

Refractory thrombotic thrombocytopenic purpura achieving complete remission with rituximab treatment.

Some patients with thrombotic thrombocytopenic purpura (TTP) are refractory to standard treatment regimens comprised of plasma exchange (PEX) and steroids. This report describes a 40-year-old woman with refractory TTP who achieved complete remission (CR) in response to rituximab. She was referred to our institution from a rural hospital with purpura of the extremities, severe thrombocytopenia, anemia, and rapidly progressive disturbance of consciousness. TTP was diagnosed based on the clinical symptoms of TTP, low ADAMTS13 activity (<0.5%), and high ADAMTS13 inhibitor (4.4 BU/ml) titers. High-dose prednisolone was immediately administered and PEX was started. This approach was initially effective, but the thrombocytopenia and disturbance of consciousness worsened on the sixth day of treatment. We considered this patient to have refractory TTP and administered weekly rituximab. CR was achieved on day 20, and the disease status of this patient has remained stable over the long term. Our experience with this patient and five others who were similarly treated at our hospital over the past eight years indicates that rituximab is effective for refractory TTP.

Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma.

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.

Glomerular cytokine expression in murine lupus nephritis.

BACKGROUND: Aberrant expression of T helper cell (Th) cytokines is believed to play a central role in the pathogenesis of systemic lupus erythematosus (SLE). While the glomerulus is one of the major targets of lupus inflammation, little is known about the cytokine expression in glomeruli. The current study aimed to explore the profiles of Th cytokine gene expressions in isolated glomeruli of lupus-prone mice. METHODS: Glomeruli were purified from lupus-prone MRL/lpr mice using the magnetic microbead method. Expressions of cytokine genes representing the Th subset and FoxP3 were examined using real-time polymerase chain reaction. Serum levels of these cytokines were also measured by enzyme-linked immunosorbent assay. MRL/n mice were used as controls. Histologic glomerular damages were scored semiquantitatively. To examine the role of TNF-α in glomerular damage, we administered etanercept, a TNF-α antagonist, into the subjects. RESULTS: Glomerular gene expressions of TNF-α in lpr mice increased with week postpartum and reached statistically significant levels at 16 weeks compared with those of the glomeruli from control mice. Expressions of IFN-γ, IL-4 and FoxP3 also increased, but the difference was not significant. There was a significant increase in serum levels of TNF-α, IFN-γ, and IL-17 and decrease in those of IL-4. Among the genes examined, TNF-α significantly correlated with glomerular damage score. Administration of etanercept did not affect glomerular cytokine expressions or proteinuria and failed to ameliorate histologic glomerular damages. CONCLUSION: Our data suggest that Th1 cytokines, especially TNF-α, are dominantly expressed in the glomeruli of lupus-prone mice, but its pathophysiological role remains unclear.

Renal outcomes in mixed proliferative and membranous lupus nephritis (Class III/IV + V): A long-term observational study.

OBJECTIVES: In this study, we aimed to assess the effect of combination of proliferative and membranous lesions (Class III + V or IV + V) on renal outcomes as an independent category distinct from Class III and IV. METHODS: We retrospectively analyzed 103 Japanese patients (14 male and 89 female) with Class III/IV LN, with or without Class V, who underwent renal biopsy and were treated at our institution. Renal endpoint was defined as doubling of serum creatinine or end-stage renal disease (ESRD). RESULTS: The number of patients in each group was as follows: pure Class III/IV, 81 patients and mixed Class III/IV + V, 22 patients. During a median follow-up period of 125.0 months, 10 patients developed renal endpoint: five had Class III/IV LN and five had a combination of Class III/IV + V. Kaplan-Meier analyses demonstrated that patients with mixed Class III/IV + V LN had significantly poorer renal outcomes than patients with Class III/IV LN. Multivariate Cox regression analyses identified serum creatinine, active and chronic lesions (A/C), and mixed Class III/IV + V) as independent risk factors for poor renal outcomes. CONCLUSIONS: This study demonstrated a combination of proliferative and membranous LN (ISN/RPS Class III/IV + V) predicts poor renal outcomes.

A case of ANCA-negative renal small-vessel vasculitis with tubulointerstitial infiltration of IgG4-positive plasma cells.

A 62-year-old male patient presented with progressive renal dysfunction for 2 months. He had elevated serum C-reactive protein and IgG4 levels with absence of anti-neutrophil cytoplasmic antibodies. A renal biopsy showed severe tubulointerstitial nephritis (TIN) with extensive infiltration of IgG4-positive plasma cells, suggesting a diagnosis of IgG4-related kidney disease (IgG4-RKD). However, the identification of a few crescentic glomeruli and necrotizing vasculitis of an interlobular artery lead to a diagnosis of renal small-vessel vasculitis. This case indicates that a careful examination is required to distinguish between IgG4-RKD and TIN caused by renal small-vessel vasculitis.

[Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

[Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm].

Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/µl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors.

[Development of acquired hemophilia A during maintenance therapy for immune thrombocytopenia].

Acquired hemophilia A (AHA) is a rare coagulation disorder caused by autoantibodies against coagulation factor VIII (FVIII). We report herein a very rare case of AHA complicated by immune thrombocytopenia (ITP). A 30-year-old woman was hospitalized with severe thrombocytopenia. Her platelet count was 5,000/µl on admission, at which time APTT was normal. ITP was diagnosed and she was treated with γ-globulin, platelet transfusion, and prednisolone at 1 mg/kg/day. She was discharged after platelet count normalization and prednisolone was tapered to 5 mg/day. During the prednisolone tapering, purpura appeared on both thighs and in the left inguinal region, and APTT was found to be prolonged. She was referred to our hospital for examination of APTT prolongation. FVIII activity was markedly decreased to 7.7% and the FVIII inhibitor was positive (1.5 BU/ml), based on which AHA was diagnosed. We carefully followed this patient without intensification of immunosuppressive therapy for 7 weeks, but her platelet count decreased from 150,000/µl to 70,000/µl and the FVIII inhibitor increased to 4 BU/ml. We therefore increased prednisolone to 30 mg/day, after which her platelet count increased and complete remission of AHA was achieved by day 42. In addition, we examined the relationship of the FVIII inhibitor and FVIII binding antibody in this case.