第 59 回神奈川腎炎研究会 入院時検査所見 尿一般 比重 PH 蛋白 蛋白定量 潜血 糖 赤血球 白血球 円柱 BJP 尿生化学 Osmo Cr Na K NAG FENa FEUN 凝固系 PT-INR APTT FIB g /g Cr - - <1/HPF 1
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1 LCr097mg dlcrp063mgdlana640xdsdna 288IUmlCH50<5U SLE dsdna 20IUml 100mg Cr21mgdl cm67kg mmHg 73 KeyWord 84
2 第 59 回神奈川腎炎研究会 入院時検査所見 尿一般 比重 PH 蛋白 蛋白定量 潜血 糖 赤血球 白血球 円柱 BJP 尿生化学 Osmo Cr Na K NAG FENa FEUN 凝固系 PT-INR APTT FIB g /g Cr - - <1/HPF 1.1/HPF なし 陰性 568 mosm/kg 109 mg/dl 131 meq/l 42 meq/l 13.1 U/L 1.9 % 39.8 % 血算 WBC ³ RBC ⁶ Hb 13.3 Plt ⁴ 21.8 網状赤血球 /μl /μl g/dl /μl < sec 368 mg/dl 生化学 TP Alb AST ALT ALP γ-gtp LDH CK UN Cr egfr UA Na K Cl Ca P Mg 6.9 g/dl 3.6 g/dl 27 IU/L 15 IU/L 158 U/L 60 U/L 208 I U/L 158 I U/L 23.7 mg/dl 2.2 mg/dl 24.6 ml/min 7.7 mg/dl 138 meq/l 3.9 meq/l 108 meq/l 8.2 mg/dl 3.2 mg/dl 2.0 mg/dl 免疫 CRP 0.22 mg/dl IgG IgG4 IgA IgM 抗RNP抗体 抗Scl抗体 抗sm抗体 抗SS-A抗体 抗SS-B抗体 抗ds-DNA抗体 1852 mg/dl 32.1 mg/ml 146 mg/dl 154 mg/dl 抗CL-β2GPI - カルジオリピンIgG抗体 18 U/ml ループスアンチコアグラント 1.16 MPO-ANCA - C3 40 mg/dl C4 <2 mg/dl CH50 <5 U/mL 17.1 免疫複合体 クリオグロブリン - 感染症 TPLA - RPR - HBsAg - HCVAb - DLST 痛散湯 ロキソニンテープ 陰性 Ga HE x100 図1 図2 85
3 腎炎症例研究 30 巻 2014 年 C3 C1q C3 C1q C3 C Fib C4 PAS x400 PAM x400 図3 図6 PAM x200 Masson x100 図4 IgG 図7 IgA IgG IgA IgM IgG I G IgG IgA IgM IgG 図5 IgG4 図8 86
4 MCTDmixed connective tissue disease) IgG IgA IgGIgAC1q C3 C4 16 PSL 40mg/day PSL 30mg/day 3 Cr 14 Cr C4 8 C3 1.5 CH CH50*10 C4*10 C3*10 Cr (Clin Exp Nephrol 9: Table IgG IM C3 C1q IgG C1q C3 EDD 1 52 F ARF UP TBM 2 23 F RTA UP F ARF UP M 4 42 F ARF UP ± F ARF UP M CKD NS UP M 7 3 M CKD UP F ARF UP M ARF UP ± TBM F CKD UP ± M CKD UP ± TBM EDD:electron-dence deposits, TBM:tubular basement membrane, M:mesangium 87
5 SLE CRP063 ANA640 dsdna288 CH50<5U SLE dsdna day cm 67kg NAG DLST IgG 1852 IgG DLST 31 mesangium mesangium IgGIgAIgM IgGIgA mesangium C1qC3 C1q C3 C4 IgGIgG4 IgG4 lupus MCTDIgG4IgA SSASSB MCTDIgG4 IgG432 IgG4 88
6 IgA SLE 40mgday 30mgday C3C4CH50 20mg lupus mesangium IgGIgM C3 C1q11 5 mesangium 3mesangium 2 lupus IgGIgA C1qC3 C4 lupus SLEmalarrash discoidrash butterflyrush 1 G4 cellular dominant patchy G4 89
7 012 G4 needlebiopsy G4 G4 1 G4 G4 outermedulla innermedullar G4 02 collapse 03 vasarecta outermedulla 04 macrophages 05 cellularg4 tubulitis mesangium matrix fibrous 60 capillary plasmacell 07 plasmacell giantcell 23 tubulitis 08fibrosis birdseye storiformpattern depositive densedeposit 09 giantcell lupus 90
8 granulomatous 10fibrosis 11 plasmacellbirdseye G granulomatous 15 16giantcell lupus 17 extraglomerular deposits lupus 3 TBM peritubularcapillaries IgG IgA IgM 18C3 C1q TBM C4 extra glomerulardeposits G4 IgG 1 4 C3C1q 19TBM densedeposit G4 deposit TBM massive deposit 20tubulesinterstitial nephritis diffuse G4 G4 negative G4 lupus granulomatous 21 IgG HE HE 91
9 04peritubularcapillaritis 05 mesangium 06 debris 07PAM 08 IgG4 09PAS 10PAM 11fiber 12Masson IgG4 lupus IgGtubules IgM 15C3C1q 16 deposit deposit 17proximaltubule electrondensedeposit 18 lamination 19 20deposit deposit (ISN/RPS SLE ISNRPS mesangiumlupusmesangium 92
10 lupus immunedeposit lupus lupus SLE SLE SLE dsdna IgG mesangium lupus peritubularcapillaries 153 lupus dsdna SLE dsdna 288 dsdna dsdna macrophages dsdna SLE dsdna SLE lupus dsdna 1 dsdna
11 1negative dsdna SLE SLE dsdna SLE SLE lupus dsdna lymphoma characterize characterize SLE SLE 1 rheumatoidfactor dsdna lupus lupus 94
12 95
13 II-2: SLE1() dsdna288iu CH50<5UANA640 SLE129 IgG4 32mg/mlGa IgG4 96
14 97
15 IgG IgM IgA 98
16 C3 C1 C4 Clin Nephrol Jun;69(6): Predominant tubulointerstitial nephritis in a patient with systemic lupus erythematosus: phenotype of infiltrating cells. Omokawa A, Wakui H, Okuyama S, Togashi M, Ohtani H, Komatsuda A, Ichinohasama R, Sawada K. Source Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan. Abstract A 63-year-old man with systemic lupus erythematosus developed tubular proteinuria. All subclasses of serum IgG increased, and the largest IgG subclass increase was IgG4. A renal biopsy showed lupus nephritis (Class II) with severe tubulointerstitial nephritis (so-called predominant tubulointerstitial lupus nephritis, an unusual form of lupus nephritis). Immunofluorescence microscopy revealed positive granular staining for IgG, C3 and C1q in the mesangium and peritubular interstitium, and along the tubular basement membranes (TBM). Electron microscopy also showed electron-dense deposits in the mesangium and TBM. Immunophenotyping of interstitial infiltrating cells disclosed a predominance of T cells. CD8- positive cytotoxic T cells infiltrated the peritubular interstitium, and some of these cells infiltrated the tubules. B cell-rich lymphoid follicles were also observed. IgG subclass analyses showed glomerular IgG1, IgG2 and IgG4 deposition, positive staining of IgG4 in the peritubular interstitium and along the TBM, and abundant IgG1-, IgG3- and IgG4-positive plasma cells in the interstitium. The patient responded well to moderate-dose steroid therapy. This is the first report of immunophenotyping of interstitial infiltrates in predominant tubulointerstitial lupus nephritis. The results suggest CD8-positive cytotoxic T cell-mediated tubular injury. Furthermore, immune complexes containing IgG4 might be one of etiologic factors. Lupus Nov;20(13): doi: / Discrepancies in glomerular and tubulointerstitial/vascular immune complex IgG subclasses in lupus nephritis. Satoskar AA, Brodsky SV, Nadasdy G, Bott C, Rovin B, Hebert L, Nadasdy T. Source Department of Pathology, The Ohio State University Medical Center, M018 Starling Loving Hall, 320 W 10th Ave, Columbus, OH 43210, USA. anjali.satoskar@osumc.edu Abstract BACKGROUND AND OBJECTIVES: Lupus nephritis is characterized by glomerular and extraglomerular immune complex deposition in the kidney. It is unclear whether the same circulating immune complexes deposit in the glomeruli and in extraglomerular structures, or whether they are pathogenetically different. Differences in the IgG subclass composition may point towards different pathways in the formation of glomerular and extraglomerular immune complexes. Therefore we investigated IgG subclass distribution in the immune complex deposits at these anatomic sites. DESIGN: A total of 84 biopsies diagnosed as lupus nephritis and classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification, were examined by direct immunofluorescence staining for IgG subclasses. The IgG subclass composition in the glomerular, tubular basement membrane (TBM) and vascular wall deposits was compared. We also correlated the presence/absence of interstitial inflammation and IgG subclasses in the TBM and vascular deposits. Lastly, we looked for correlation between staining for IgG subclasses and complement C1q and C3 staining. RESULTS: IgG staining was present in the TBM in 52/84 biopsies, and in the vascular walls in 40/84 biopsies. IgG subclass distribution was discrepant between glomerular and TBM deposits in 36/52 biopsies, and between glomerular and vascular deposits in 27/40 biopsies. Interstitial inflammation did not correlate with the presence of IgG staining or distribution of IgG subclasses in the TBM. Interstitial inflammation was more common in biopsies of African-American patients than Caucasian patients. The IgG subclass staining correlated with C1q staining in all the three compartments. CONCLUSIONS: The antibody composition of the glomerular and extraglomerular immune complex deposits appear to differ from each other. They may not represent the same preformed immune complexes from the circulation. It is likely that their pathogenesis and site of formation are different. Tubulointerstitial nephritis, diffuse cortex/medulla= 9/1, global scelrosis/glomeruli=4/19 bird s eye pattern IgG(+), IgM(±), IgA(±), C3(±), C1q(+): mesangial & TBM pattern C1q(+) TBMdense deposits IgG4. 99
17 100
18 101
19 IgG IgM IgA C1q C4 C3 Fib 102
20 103
1 2 2 ANCA pouci immune IgG C3 ANCA 68 '01 '02 7 UN 14mg/dl, Cr 0.7 mg/dl, -, - ' UN 45mg/dl, Cr 2.4 mg/dl, Ht 29.5%, 4+, cm 61
1 2 2 ANCApouci immune IgG C3 ANCA 68 '01 '02 7 UN 14mg/dl, Cr 0.7 mg/dl, -, - '03 2 3 31 UN 45mg/dl, Cr 2.4 mg/dl, Ht 29.5%, 4+, 3+ 4 14 156.0 cm 61.5 kg 36.9 158/92 mmhg 90 1. ANCA 2. 3. IgG4 deposit
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