A case of refractory cutaneous polyarteritis nodosa in a patient with hepatitis B carrier status successfully treated with tumor necrosis factor alpha blockade

We describe a patient with refractory cutaneous polyarteritis nodosa (CPAN) with hepatitis B virus (HBV) carrier status who was successfully treated with tumor necrosis factor alpha (TNF-α) blockade, using etanercept, and we review 5 similar cases. We administered etanercept because of the occurrence of repeated flares despite aggressive therapy. C-reactive protein normalization; prednisolone dose-sparing; and absence of any adverse events, including HBV reactivation with nucleotide analogue administration, or renal dysfunction, have been achieved for 8 months. TNF-α blockade should be considered for intractable CPAN. © 2012 Japan College of Rheumatology.In Press →　出版者照会後に全文を公開

A case report of crystalline light chain inclusion-associated kidney disease affecting podocytes but without Fanconi syndrome

RATIONALE:Crystalline light chain inclusion-associated kidney disease affects mainly tubular epithelial cells and is often clinically manifested as Fanconi syndrome. However, only very few case reports about the crystalline deposits within the podocytes are available, and the nature of the pathogenic monoclonal light chain implicated in these cases is still unknown. We report a case of crystalline inclusion-associated kidney disease manifested as crystalline podocytopathy in which we identified the complete structure of the pathogenic monoclonal light chain as belonging to the germ-line gene of Vκ1-39.PATIENT CONCERNS:We describe a 65-year-old woman with crystalline light chain inclusion-associated kidney disease showing mild proteinuria and renal insufficiency with monoclonal gammopathy of undetermined significance without Fanconi syndrome. She had crystalline inclusions mainly within podocytes, tubular epithelial cells and histiocytes in the kidney. Light microscopy showed vacuolation of podocytes and tubular epithelial cells, while eosin negative pale needle-like crystals were present within these cells. Electron microscopy showed accumulation of club-like crystals with high electron density in podocytes, proximal tubular epithelial cells and interstitial histiocytes. Clonal analysis revealed that a pathogenic monoclonal light chain was derived from germline gene, Vκ1-39.DIAGNOSES:The diagnosis of crystalline light chain inclusion-associated kidney disease was made.INTERVENTIONS AND OUTCOMES:Bortezomib and dexamethasone were started and her renal function improved to eGFR 36 mL/min/1.73 m after 9 courses of therapy.LESSONS:Patients with light chain crystalline podocytopathy may have a similar pathogenic monoclonal light chain derived from the same germline gene, Vκ1-39, to that of patients with light chain proximal tubulopathy

ループス腎炎の増殖性病変とワイヤーループ病変におけるケモカインの関与

金沢大学附属病院MRL/lpr mouse-derived monoclonal IgG3 antibody-producing hybridomas, 2B11.3 and B1, were injected into wild type mice to induce glomerular endocapillary hypercellularity and wire-loop lesions, respectively. The former had enhanced expression of CCL2, CCL3, CCR2, CCR5, and CX3CR1 than the latter. It was mainly glomerular macrophages that expressed them in endocapillary hypercellularity. Using chemokine receptor-deficient mice or a selective CCR5 antagonist, maraviroc, we showed that CCR2 and CCR5 regulated glomerular macrophage infiltration and contributed to the development of glomerular endocapillary hypercellularity, and that CCR5 inhibition could be a specific therapy for endocapillary hypercellularity in lupus nephritis.ループス腎炎モデルであるMRL/lprマウス由来の腎炎原性モノクローナルIgG3産生ハイブリドーマを野生型マウスに投与し、管内細胞増多病変とワイヤーループ病変を個別に形成した。前者は後者よりCCL2、CCL3、CCR2、CCR5、CX3CR1の発現が亢進し、糸球体に浸潤したマクロファージが主にこれらを発現していた。このハイブリドーマと、ケモカイン受容体欠損マウスや選択的CCR5阻害薬のマラビロクを用いて、CCR5とCCR2が管内細胞増多病変の形成に関与し、特にCCR5が管内細胞増多病変の治療ターゲットとなりうることを示した。研究課題/領域番号:20K17424, 研究期間(年度):2020-04-01 – 2022-03-31出典：研究課題「ループス腎炎の増殖性病変とワイヤーループ病変におけるケモカインの関与」課題番号20K17424（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-20K17424/20K17424seika/）を加工して作

「ポドサイトは補体H因子を産生し糸球体内皮下の免疫複合体沈着物を除去しうる」

第18回　高安賞最優秀論文賞受賞 Scientific Reports 2019 May 27; 9(1): 7857　2019 年5月掲載 Takeshi Zoshima, Satoshi Hara, Masakazu Yamagishi, Ira Pastan, Taiji Matsusaka, Mitsuhiro Kawano & Michio Nagat

De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report

Abstract Background Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. Case presentation We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. Conclusions SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly