Granulomatosis with polyangiitis in a patient with a thoracic vertebral lesion: a case report.

Granulomatosis with polyangiitis is a systemic, small vessel vasculitis associated with the anti-neutrophil cytoplasmic antibody. We herein report a case of granulomatosis with polyangiitis with paravertebral lesions. A 69-year-old man presented to our hospital with fever, back pain, and myalgia. A computed tomography scan showed multiple lung nodules, while magnetic resonance imaging revealed soft tissue shadows around a thoracic vertebral lesion. A laboratory examination revealed positive myeloperoxidase anti-neutrophil cytoplasmic antibody. He was diagnosed with granulomatosis with polyangiitis. He was treated with oral glucocorticoid and intravenous cyclophosphamide, and the shadows resolved. Physicians should consider granulomatosis with polyangiitis in cases with paravertebral lesions.

A case of myeloperoxidase-antineutrophil cytoplasmic antibody and anticardiolipin antibody-positive pyogenic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa (PAPASH) syndrome with colitis.

A previous case report of colitis and serine proteinase 3-antineutrophil cytoplasmic antibody positivity in pyogenic arthritis, pyoderma gangrenosum (PG), acne and hidradenitis suppurativa (PAPASH) syndrome with colitis has been published. Herein, we report a similar case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity. A 26-year-old man presented with recurrent aseptic pyogenic arthritis, acne, hidradenitis suppurativa and PG. Lower gastrointestinal endoscopy was performed, and colitis was observed. No PSTPIP1 gene mutation was found in the gene-sequencing test. Based on these findings and prior case reports, we diagnosed the patient with PAPASH syndrome, a PAPA spectrum disorder complicated by colitis. This patient had PAPASH syndrome with colitis and was MPO-ANCA and anticardiolipin antibodies-positive; it is unclear whether these antibodies play a role in this disease, but it may provide clues to further elucidate its pathogenesis.

Disseminated Intravascular Coagulation-like Reaction after Rituximab Infusion in a Patient with Nephrotic Syndrome.

Several case series have suggested that rituximab is efficacious in adult patients with minimal change disease. We herein report a case of disseminated intravascular coagulation-like reaction after rituximab infusion in a patient with nephrotic syndrome. A 58-year-old Japanese man with minimal change disease diagnosed 15 years earlier was started on rituximab to prevent relapse of nephrotic syndrome when he presented to our clinic with low albuminemia, massive proteinuria, and leg edema. Eleven days after rituximab infusion, he presented with abdominal pain, appetite loss, and tarry stool. A laboratory examination revealed severe thrombocytopenia and coagulopathy, and upper gastrointestinal endoscopy revealed multiple hemorrhagic ulcers in his esophagus and stomach. The patient died two days later. Physicians should consider disseminated intravascular coagulation-like reaction when encountering cases with thrombocytopenia after rituximab infusion for any disease.

A mutation in transcription factor MAFB causes Focal Segmental Glomerulosclerosis with Duane Retraction Syndrome.

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset FSGS, but the etiologies of most adult cases remain unknown. Genetic studies of monogenic syndromic FSGS exhibiting extra-renal manifestations have uncovered an unexpected biological role for genes in the development of both podocytes and other cellular lineages. To help define these roles, we studied two unrelated families with FSGS associated with Duane Retraction Syndrome, characterized by impaired horizontal eye movement due to cranial nerve malformation. All four affected individuals developed FSGS and Duane Retraction Syndrome in their first to second decade of life, manifested as restricted abduction together with globe retraction and narrowed palpebral fissure on attempted adduction. Hypoplasia of the abducens nerves and hearing impairment occurred in severely affected individuals. Genetic analyses revealed that affected individuals harbor a rare heterozygous substitution (p.Leu239Pro) in MAFB, a leucine zipper transcription factor. Luciferase assays with cultured monocytes indicated that the substitution significantly reduced transactivation of the F4/80 promoter, the known MAFB recognition element. Additionally, immunohistochemistry indicated reduced MAFB expression in the podocytes of patients. Structural modeling suggested that the p.Leu239Pro substitution in the DNA-binding domain possibly interferes with the stability of the adjacent zinc finger. Lastly, podocytes in neonatal mice with p.Leu239Pro displayed impaired differentiation. Thus, MAFB mutations impair development and/or maintenance of podocytes, abducens neurons and the inner ear. The interactions between MAFB and regulatory elements in these developing organs are likely highly specific based on spatiotemporal requirements.

Comparison of Renal Outcome among Japanese Patients with or without Microangiopathic Hemolysis in Malignant Phase Hypertension: A Single-Center Retrospective Study.

BACKGROUND/AIMS: Although microangiopathic hemolysis (MAH) is a well-known complication of malignant phase hypertension (MPH), only less data on whether MAH in MPH predicts renal outcome exist. Therefore, we evaluated whether MAH was associated with the renal outcome in patients with MPH. METHODS: We conducted a single-center, retrospective, cohort study. Data from 35 patients diagnosed with MPH between October 1998 and January 2015 were analyzed. MPH was defined as the presence of a diastolic blood pressure of ≥120 mm Hg and grades III/IV hypertensive retinopathy according to the Keith-Wagener-Barker classification. MAH was defined as the presence of a low platelet count (<150 × 109/L) together with either an elevated level of lactate dehydrogenase (LDH; >220 U/L), or the presence of schistocytes, or both and the normalization of platelet and LDH level or schistocyte levels after adequate blood pressure control was achieved. The primary outcome was dialysis induction. RESULTS: Fifteen patients had MAH. Those with MAH had significantly severe renal dysfunction at the onset of MPH. The length of follow-up (median, interquartile range) of patients with MAH and those without MAH were 30 (16-94) and 48 (25-115) months, respectively. Dialysis was induced in 9 of 15 patients with MAH and in 6 of 20 patients without MAH. Renal survival in patients with MAH was worse than that in those without, but this was not statistically significant (p = 0.08). By multivariate Cox regression analysis, MAH was not shown to contribute to dialysis induction. CONCLUSION: MAH did not predict renal outcome in MPH.

New onset of immunoglobulin G4-related disease in a patient with relapsing polychondritis.

Relapsing polychondritis (RP) is a rare systemic autoimmune disorder characterized by the episodic and progressive deterioration of cartilage inflammation. Approximately 30% patients with RP have concurrent disease. However, there have been no previous reports of RP complicated by immunoglobulin G4-related disease (IgG4-RD). Here we report the case of a 67-year-old male who developed IgG4-RD approximately 20 years after RP diagnosis. The association between IgG4-RD and RP remains unclear.

Absence of mesangial C1q deposition is associated with resolution of proteinuria and hematuria after tonsillectomy plus steroid pulse therapy for immunoglobulin a nephropathy.

INTRODUCTION AND AIMS: Deposition of C1q occurs in 0 to 45% of patients with IgAN. In order to identify whether mesangial C1q deposition in IgAN is a novel marker for the response to tonsillectomy plus steroid pulse therapy (TSP), we studied the association between mesangial C1q deposition in IgAN and the remission rate after TSP therapy for IgAN. METHODS: We conducted a retrospective cohort study at a single Japanese center. We analyzed data on 110 patients diagnosed with IgA nephropathy who received TSP between January 2003 and December 2012. Positive C1q findings were defined as diffuse mesangial C1q deposition. The study outcome was the resolution of abnormal urinary findings and was defined as negative proteinuria and negative occult blood 1 year after steroid pulse therapy. RESULTS: In all enrolled cases, 69 patients (62.7%) went into remission. Ten out of 24 (41.7%) C1q-positive patients experienced remission, and 59 out of 86 (68.6%) C1q-negative patients experienced remission. Multiple logistic regression model analysis showed that the absence of C1q deposition increased the odds ratio for remission (odds ratio 4.41; 95% confidence interval 1.33-15.75, p = 0.017). CONCLUSIONS: These results suggest that the absence of diffuse C1q deposition in the mesangial area of the glomerulus in patients with IgA nephropathy is a positive predictive sign for a response to TSP and is associated with the resolution of urinary abnormalities 1 year after TSP.

Impact of the new risk stratification in the 2011 Japanese Society of Nephrology clinical guidelines for IgA nephropathy on incidence of early clinical remission with tonsillectomy plus steroid pulse therapy.

BACKGROUND: In 2011, the Japanese Society of Nephrology (JSN) published new clinical guidelines for IgA nephropathy (IgAN) with a new risk stratification based on clinical and histological severity. For classification, patients are divided into four groups (low, medium, high, and very high risk). However, differences in responsiveness to each treatment among different groups remain unclear. We evaluate the responsiveness of tonsillectomy plus steroid pulse (TSP) therapy using the new risk stratification. METHODS: We retrospectively reviewed 111 IgAN patients with TSP therapy between January 2003 and January 2013. Study patients were divided into three groups [low- (n = 40), medium- (n = 43) and high-/very high-risk group (n = 28)]. The primary outcome was clinical remission (CR). The observation period was 1 year following tonsillectomy. RESULTS: 57 out of 111 patients (51.4 %) reached CR. The CR incidence was 70.0, 41.9 and 39.3 % (the low-, the medium- and the high-/very high-risk group, respectively). The incidence of CR was significantly higher in the low-risk group (P = 0.013). In a multivariate logistic regression analysis, both the medium- and the high-/very high-risk group showed significantly lower incidence of inducing CR than the low-risk group [(odds ratio 0.324; 95 % confidence interval 0.106-0.939, P = 0.041) (odds ratio 0.239; 95 % confidence interval 0.058-0.910, P = 0.040), respectively]. CONCLUSIONS: The new risk stratification in the 2011 JSN clinical guidelines for IgAN had a positive impact on early CR of TSP therapy.

Four mild but refractory cases of pemphigus foliaceus successfully treated with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is a potential second line of therapy for pemphigus, with increasing evidence of its effectiveness and safety, although oral corticosteroids remain the first treatment for pemphigus. IVIG is usually applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV). Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein 1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant to corticosteroids and require long-term treatment to control the disease, leading to various adverse effects. IVIG was used in patients with relatively mild PF, who were resistant to therapies with corticosteroids and dapsone. We assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured anti-Dsg1 antibody indices by enzyme-linked immunosorbent assay, before and 4 months after IVIG. Four Japanese female PF patients (57.3 ± 8.6 years) were treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days) in combination with the previous therapies. Within 1-2 months of addition of IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also markedly decreased. For 2 years after IVIG, no apparent exacerbation was observed. Anti-Dsg1 antibody indices decreased in all cases during the 2 years. IVIG could be a potential treatment for not only severe cases of PV but also mild and refractory cases of PF. IVIG may trigger the shift from intractable condition to remission via non-pathogenic anti-Dsg1 antibodies or some mechanisms excluding anti-Dsg1 antibody.

Renal sarcoidosis with limited lung manifestations expressing Propionibacterium acnes antigens in the affected tubulointerstitium.

Sarcoidosis is a granulomatous multisystemic disorder of unknown origin that can affect the kidneys. Previous reports from Japan and Europe have indicated a link between Propionibacterium acnes infections and sarcoidosis. Here, we present the case of a 68-year-old woman with hypercalcemia and renal failure. A kidney biopsy was performed, which showed granulomatous tubulointerstitial nephritis with a large nonnecrotic nodule that contained mononuclear inflammatory cells and multinucleated giant cells. Subsequent immunohistochemical analysis revealed intracytoplasmic structures, which strongly indicated the presence of the P acnes antigen. Treatment with methylprednisolone ameliorated the patient's hypercalcemia and renal failure. This case report emphasizes the potential of chronic P acnes infection to cause sarcoidosis.

Aldosterone mediates glomerular inflammation in experimental mesangial proliferative glomerulonephritis.

BACKGROUND: The renoprotection of the mineralocorticoid receptor antagonist (MRA) is considered to be mainly via its antifibrotic activity, and the possibility that it may also have antiinflammatory effects has not been studied. We tested the hypothesis that MRA might influence the inflammatory changes that accompany experimental glomerular injury. METHODS: Administration of vehicle (control) or a selective MRA, eplerenone (50 mg/kg x 2 times/day) was started 7 days (-7d) before induction of anti-Thy-1.1 glomerulonephritis. Kidney samples were evaluated serially over a 12-day period for the presence of cell proliferation, macrophage infiltration, mesangial cell phenotypic activation and expression of the chemokine monocyte chemoattractant protein-1 (MCP-1). RESULTS: MRA did not prevent the mesangiolysis associated with anti-Thy-1 antibody. However, MRA significantly inhibited MCP-1 expression, glomerular macrophage infiltration and mesangial phenotypic activation (alpha-smooth muscle actin expression). CONCLUSION: MRA alters glomerular inflammation and mesangial cell activation in experimental glomerular injury. MRA may be a novel way to treat acute glomerular diseases.

Reversible posterior leukoencephalopathy syndrome after blood transfusion in a patient with end-stage renal disease.

A 42-year-old female end-stage renal disease (ESRD) patient with reversible posterior leukoencephalopathy syndrome (RPLS) post-transfusion during initiation of hemodialysis is reported. Eleven days after the onset of illness, we diagnosed encephalopathy as a grand mal seizure resulting from diffuse cerebral edema. One reason for the delayed diagnosis was that her symptom, a throbbing headache that occurred during her first dialysis, indicated dialysis disequilibrium syndrome. We must bear in mind that a small amount of transfusion could cause RPLS even during the first dialysis. To our knowledge, this is the first case report on RPLS after blood transfusion in an ESRD patient.

Sharp edge wavelength filters utilizing multilayer photonic crystals.

A novel configuration of dielectric multilayer wavelength filters for enabling sharp cut-off characteristics is proposed. By applying perturbations to the multilayer structures such as corrugation or lateral film isolation, deep optical stopbands can be created as a result of the coupling between the obliquely and horizontally propagating light waves. Numerical simulation by FDTD revealed that the proposed structure had approximately two to three times larger decay constants than that of unmodulated flat multilayer.

Differential interference contrast microscope using photonic crystals for phase imaging and three-dimensional shape reconstruction.

We present a differential interference contrast microscope using photonic crystals capable of real-time capture of both phase and amplitude components independently without moving parts. Unlike previous methods using rotating polarizers to discriminate each component, we propose using a special camera equipped with an arrayed polarizer whose instant polarization measurement allows real-time acquisition of the phase gradient information. A two-image algorithm is used to reconstruct the phase two-dimensional distribution of biological samples from the gradient information with a transmission-type microscope. We also talk about deducing a sample's three-dimensional shape for a reflection-type microscope. The efficiency of the method is demonstrated experimentally.

Cutting edge: perforin down-regulates CD4 and CD8 T cell-mediated immune responses to a transplanted organ.

Perforin mediates target cell apoptosis by CTLs and NK cells. Although perforin expression correlates strongly with acute allograft rejection, perforin-deficient mice reject allografts with the same kinetics as wild-type recipients. In this study, we tested the hypothesis that while perforin is dispensable for acute rejection, it is essential for down-regulating the alloimmune response by inducing the apoptosis of host immune cells. Using a skin transplantation model, we found that perforin-deficient mice are resistant to the induction of allograft acceptance by agents that block T cell costimulation. Failure to induce allograft acceptance in these mice was observed irrespective of whether the alloimmune response was CD4 or CD8 T cell-mediated and could be attributed to defective apoptosis of activated CD4 and CD8 T cells. In contrast, perforin did not influence T cell proliferation. Therefore, perforin is an essential immunoregulatory molecule that may be required for the induction of transplantation tolerance.