Txhawm rau zam kev mob raum mob hnyav: Kev Tshaj Tawm Ntawm Thomsen-Friedenreich Antigen Ntawm Lub Raum Tubules Ntawm Tus Neeg Mob Nrog Capnocytophaga Kab Mob

Takahiro Uchida, Takashi Oda, Dan Inoue, Shuhei Komatsu, Tadasu Kojima, Tomohiro Tomiyasu, Noriko Yoshikawa thiab Muneharu Yamada

Abstract:Kab mob raumnrog neuraminidase-ua cov kab mob tuaj yeem ua raumob raum raug mob(AKI). Peb nyob ntawm no qhia txog ib tug poj niam muaj hnub nyoog 74- xyoo uas tau tsim AKI thaum lub caijCapnocytophagakab mob, ib tug kab mob uas tsim neuraminidase. Lub raum biopsy pom cov tubulointerstitial raug mob nrog los ntawm kev khi tshwj xeeb ntawm fluorescence-conjugated peanut lectin rau cov tubular epithelial hlwb, qhia tias muaj Thomsen-Friedenreich antigen (T-antigen) ntawm cov tubules. Txawm hais tias AKI feem ntau pom nyob rau hauv cov neeg mob kisCapnocytophaga, me ntsis paub txog nws etiology thiab txuam nrog pathology. Cov ntaub ntawv no qhia tias kev raug mob tubulointerstitial tshwm sim los ntawm kev tsim tawm neuraminidase thiab ua rau T-antigen raug yog ib qho txheej txheem ntawmCapnocytophagakis tau tus kab mob AKI.

Ntsiab lus:Mob raum raug mob, Capnocytophaga, Thomsen-Friedenreich antigen, thrombotic microangiopathy,lub raum ua haujlwm

Yog xav paub ntxiv thov hu rau:joanna.jia@wecistanche.com

cistanche acteosides kho mob raum kab mob Capnocytophaga, nyem qhov no kom tau txais cov qauv

Taw qhia

Capnocytophagasp. yog tus kab mob Gram-negative rod-zoo li tus kab mob uas pom nyob rau hauv lub qhov ncauj ntawm cov dev thiab miv thiab feem ntau raug cais tawm ntawm cov neeg mob uas kis kab mob tom qab raug tom los yog khawb los ntawm cov tsiaj xws li (1). Cov kab mob tshwm sim los ntawm cov kab mob no feem ntau tshwm sim ua rau muaj kev phom sij rau lub neej nrog kev mob ntshav siab (septic shock) thiab / lossis septic disseminated intravascular coagulation (DIC), thiab kev tuag ntawm cov neeg mob no tau tshaj tawm siab (2).

Mob raum raug mob(AKI) kuj tau pom ntau zaus hauv chav kawmCapnocytophagakis kab mob thiab qee zaum yuav tsum tau kho lub raum hloov. Hypotension thiab DIC yog suav tias yog qhov tseem ceeb ua rauCapnocytophagakab mob-induced AKI (2), tab sis qhov tshwm sim ntawm thrombotic microangiopathy (TMA) los yog mob tubular necrosis tau piav qhia hauv qee cov lus ceeb toom (3, 4). Txawm li cas los xij, me ntsis paub txog cov txheej txheem lossis pathology cuam tshuam nrogCapnocytophagakis tau tus kab mob AKI.

Muaj ntau yam ua rau TMA, suav nrog kev kis kab mob. Shiga toxin-ua Escherichia coli yog qhov paub zoo tshaj plaws ntawm TMA nrog raws plab. Cov neeg mob feem ntau tsim AKI, thiab cov neeg mob zoo li no tau kuaj pom tias muaj hemolytic uremic syndrome. Hauv qhov sib piv, cov kab mob uas ua rau cov kab mob neuraminidase tuaj yeem ua rau TMA (thiab lwm hom mob raum raug mob) yam tsis muaj raws plab, qhov uas raug Thomsen-Friedenreich antigen (T-antigen) suav tias yog lub luag haujlwm tseem ceeb (5).

Peb nyob ntawm no qhia tus neeg mob nrog AKI tshwm sim los ntawm amob raumnrogCapnocytophaga, uas yog cov kab mob uas tsim cov neuraminidase. Tus neeg mob no nthuav tawm nrog septic shock thiab DIC; Txawm li cas los xij, lub raum biopsy pom tau tias muaj kev raug mob ntawm tubulointerstitial nrog rau qhov tshwj xeeb khi ntawm fluorescein isothiocyanate (FITC)-conjugated peanut lectin mus rau tubular epithelium, qhia tias T-antigen raug koom nrog hauv chav kawm ntawm AKI.

Case Report

Ib tug poj niam muaj hnub nyoog {{0}} xyoo uas raug kho mob ntshav qab zib mellitus tshwm sim ua npaws, xeev siab, thiab raws plab, thiab raug xa mus rau peb lub tsev kho mob. Nws lub raum ua haujlwm hauv lub raum yog qhov qub, piv txwv li proteinuria tsis tau sau tseg, thiab nws cov ntshav creatinine yog 0.54 mg / dL. Thaum nkag, nws cov ntshav siab yog 76/40 mmHg, thiab nws lub cev kub yog 34.5 degree. Nws tau raug tom nws tus ntiv tes los ntawm nws tus dev peb hnub ua ntej nkag.

Nws cov txiaj ntsig kev kuaj sim tau muab sau tseg hauv Table. Kev ntsuam xyuas ntshav tau pom tias muaj cov tshuaj tiv thaiv hemolytic. Muaj qhov tseem ceeb thrombocytopenia (platelet suav: 1.3 × 104 / μL) nrog rau qhov txawv txav ntawm cov ntshav coagulation system, qhia DIC. Nws kuj muaj mob hnyav AKI (serum creatinine: 3.34 mg / dL; ntshav urea nitrogen: 45.5 mg / dL) thiab mob siab. Kev nce ntau ntawm C-reactive protein thiab procalcitonin tau sau tseg, thaum qib ntawm immunoglobulins (Igs) thiab cov khoom ntxiv tau zoo li qub. Nws antinuclear antibody titer tsuas yog nce me ntsis. Kev urinalysis tsis tuaj yeem ua tau vim nws yog anuric. Cov quav kab lis kev cai tsuas yog kuaj pom cov nroj tsuag ib txwm muaj.

Tus neeg mob txoj kev kho mob tau pom nyob rau hauv daim duab 1. Nws tau kuaj pom tias muaj septic shock thiab DIC thiab tam sim ntawd pib kho tshuaj tua kab mob nrog meropenem thiab clindamycin, nrog rau kev tswj hwm vasopressors, thrombomodulin alfa, thiab platelet transfusion. Txawm li cas los xij, nws tau tsim purpura fulminans hauv nws lub ntsej muag thiab ntiv tes thiab pom tias muaj kev vam meej ntxiv ntawm AKI. Kev kho lub raum hloov (thaum pib txuas ntxiv hemodiafiltration tom qab hemodialysis tsis tu ncua) yog li ua txij hnub 2 ntawm kev mus pw hauv tsev kho mob. Ob peb hnub tom qab,Capnocytophagasp. raug cais tawm ntawm nws cov ntshav kab lis kev cai, thiab cov tshuaj tua kab mob tau hloov mus rau ampicillin / sulbactam.

Nws qhov kev mob tshwm sim tom qab tau zoo lawm, thiab kev kho lub raum hloov tau tiav 12 hnub tom qab pib; Txawm li cas los xij, nws lub raum tsis ua haujlwm (serum creatinine, 1.1 mg / dL; kwv yees glomerular filtration rate, 37.9 mL / min / 1.73 m 2 ) thiab cov proteinuria loj heev (2-3 gram ib hnub) txuas ntxiv. Txawm hais tias schistocytes tsis tau kuaj pom hauv cov ntshav smear, cov tshuaj tiv thaiv hemolytic tau rov pom dua ntawm kev kuaj ntshav niaj hnub. Kev kuaj zis pom tsuas yog me me isomorphic hematuria (1-4 cov qe ntshav liab / lub zog siab), tab sis cov ntshav urinary occult yog qhov zoo, qhia tias muaj qhov tshwm sim tsis tseeb.

Kev tsom xam lub teeb pom kev zoo ntawm cov ntu los ntawm lub raum biopsy tau ua percutaneously txog 2 lub hlis tom qab kab mob tshwm sim pom 15 glomeruli yam tsis muaj cov tsos mob ntawm tus mob ntshav qab zib nephropathy. Plaub glomeruli tau sclerotic thoob ntiaj teb, thiab ib qho ntawm cov glomeruli ntxiv yog segmentally sclerotic. Tsis tas li ntawd, kev raug mob ntawm tubulointerstitial tseem ceeb tau pom (Daim duab 2A), thiab qhov tso tawm ntawm hemosiderin tau pom nyob rau hauv qee cov tubular epithelial hlwb (Fig. 2B). Cov nonsclerotic glomeruli tsis pom kev hloov pauv lossis thickening ntawm cov phab ntsa glomerular capillary (Fig. 2C). Tsis pom muaj kab mob capillaritis lossis thrombi hauv peritubular capillaries (Daim duab 2D). Immunostaining pom tsis muaj Ig los yog ntxiv deposition nyob rau hauv lub glomeruli, thiab electron microscopy tsis pom muaj electron-dense deposits los yog cov cim ntawm TMA, xws li glomerular endothelial o, widening ntawm lub subendothelial qhov chaw, los yog ob contours ntawm lub glomerular qab daus daim nyias nyias (Daim duab. 2 E). Nyob rau hauv sib piv, focal IgM deposition tau pom ntawm tubular epithelial hlwb (Fig. 3A). Tsis tas li ntawd, FITC-conjugated txiv laum huab xeeb lectin tau pom tshwj xeeb khi rau tubular epithelial hlwb (Fig. 3B, C), tab sis tsis muaj kev khi tshwj xeeb ntawm FITC-conjugated peanut lectin ntawm tubular epithelial hlwb ntawm lub raum tswj cov ntaub so ntswg (Fig. 3D).

Muab cov kev tshawb pom saum toj no, kev kuaj mob pathological ntawm mob tubular raug mob nrog T-antigen raug. Tom qab ntawd, tus neeg mob tau txais kev kho mob nrog angiotensin II receptor blocker. Ob xyoos tom qab lub raum biopsy, nws cov ntshav creatinine yog 1.32 mg / dL (kwv yees glomerular filtration rate, 30.4 mL / min / 1.73 m2), thiab nws cov protein excretion rate yog 0.5 g / hnub, nrog rau tsis muaj sediment txawv txav ntawm kev kuaj zis.

Kev sib tham

Cov neeg mob uas muaj tus kab mob Capnocytophaga feem ntau tsim AKI, tab sis cov txheej txheem cuam tshuam thiab pathology tsis tau tshawb xyuas zoo. Muaj ib kis dhau los ntawm AKI tshwm sim los ntawmCapnocytophagabacteremia uas kuv-anxiolysis, nrog rau tubular necrosis, tau pom (4). Cov ntaub ntawv tam sim no muaj teeb meem nrog septic shock thiab DIC, ob qho tib si uas yuav cuam tshuam rau lub raum pathology; Txawm li cas los xij, rau peb txoj kev paub, qhov no yog thawj kis ntawm tus neeg mob uas qhia txog kev raug mob tubulointerstitial nrog los ntawm kev raug T-antigen ntawm lub raum cov ntaub so ntswg.

Cov neeg mob uas muaj cov kab mob neuraminidase tsim tawm tuaj yeem tsim TMA. Nws tau txiav txim siab hauv qhov chaw no tias T-antigen, uas tau muab zais rau hauv ib txwm muaj los ntawm neuraminic acid, raug nthuav tawm los ntawm kev ua haujlwm neuraminidase. Preformed IgM cov tshuaj tiv thaiv kab mob ntawm tus tswv tsev muaj tus kab mob ces khi rau T-antigen tshwm sim ntawm cov ntshav liab, platelets, thiab endothelial hlwb, yog li pib ua ib qho xwm txheej ua rau TMA (5). Tus kab mob Streptococcus pneumoniae yog ib qho kev paub zoo ntawm TMA, uas tau tshaj tawm feem ntau cuam tshuam nrog sepsis / bacteremia (6). Txawm li cas los xij, muaj ntau yam kab mob uas muaj kev ua haujlwm neuraminidase, thiab nthuav dav,Capnocytophagasp. yog ib hom kab mob zoo li no (7, 8).

S. pyogenes yog lwm cov kab mob neuraminidase uas yuav ua rau TMA ntawm cov txheej txheem zoo sib xws (9). Tseeb tiag, peb tsis ntev los no tau ntsib ib qho kev nthuav dav ntawm tus neeg mob nrog S. pyogenes kab mob, nyob rau hauv uas concurrence ntawm TMA nrog zoo tubular FITC-conjugated txiv laum huab xeeb lectin staining thiab post-streptococcal mob glomerulonephritis nrog zoo glomerular staining ntawm nephritis-txog nephritis plasminogenic receptor, streptococcal protein, thiab lwm yam kev ua plasmin (10) tau pom (cov ntawv sau hauv kev npaj). T-antigen exposure-induced TMA tuaj yeem tshwm sim ua ke nrog lwm hom kev mob raum.

Cov txiv laum huab xeeb lectin tau pom tias muaj kev sib raug zoo rau T antigen, yog li kev raug T-antigens tuaj yeem raug soj ntsuam siv cov txiv laum huab xeeb lectin raws li kev sojntsuam. Siv biotin-labeled peanut lectin thiab FITC-conjugated streptavidin raws li kev sojntsuam, Shimizu et al. Ua kom pom qhov tshwm sim ntawm T-antigen hauv glomeruli thiab cov tubules ntawm tus neeg mob S. pyogenes-associated hemolytic uremic syndrome (9). Hauv qhov sib piv, siv FITC sau cov txiv laum huab xeeb lectin ua kev sojntsuam, Alon li al. pom tau tias muaj T-antigen raug tsuas yog nyob rau hauv tubular epithelium ntawm tus neeg mob nrog S. pneumoniae-associated hemolytic uremic syndrome, zoo ib yam li cov kev tshawb pom ntawm tus neeg mob tam sim no (11). Peb tus neeg mob tsis tau pom cov kab mob pathological ntawm TMA; Txawm li cas los xij, kev nce qib ntawm lactate dehydrogenase, nrog rau kev rov ua dua cov tshuaj hemolytic ntawm kev kuaj ntshav, thiab qhov tshwm sim tsis zoo ntawm cov ntshav tso zis, tag nrho cov lus qhia ntawm TMA, tau pom. Tsis tas li ntawd, kev tso tawm ntawm hemosiderin nyob rau hauv tubular epithelial hlwb, uas yog ib qho kev tshwm sim ntawm hemolysis, kuj tau pom. Schistocytes tsis tau kuaj pom nyob rau hauv tus neeg mob cov ntshav smear, tab sis qhov no yuav yog vim qhov tsis zoo ntawm qhov kev sim no. Yog li, nws muaj peev xwm hais tias TMA qhov txhab tau tshwm sim tab sis tsis pom los ntawm percutaneous koob biopsy. Nws kuj tseem muaj peev xwm hais tias lub sij hawm ntawm lub raum biopsy tau ua cuam tshuam rau lub raum histology, vim qhov kev kuaj mob ntawm tus neeg mob tam sim no tsis tau ua hauv chav kho mob thaum ntxov.

Lwm qhov teeb meem tseem ceeb yog hais txog kev kho mob. Txawm hais tias peb pib kuaj tus neeg mob nrog septic shock thiab DIC, qhov ua tau ntawm thrombotic thrombocytopenic purpura tsis tuaj yeem txiav txim siab tag nrho. Txawm li cas los xij, raws li theem nrab TMA cuam tshuam los ntawm kev kis kab mob ntau dua, peb tsis ua plasmapheresis. Hloov chaw, peb xav tias yuav tsum tau txhaj cov ntshav platelet tsim nyog vim tias tus neeg mob tau pom cov thrombocytopenia hnyav (1.3 × 104 / μL) ntawm kev nkag, thaum peb yuav tsum tau ua cov txheej txheem invasive, xws li central venous catheter insertion. Thaum kho cov neeg mob nrogTus kab mob Capnocyanophage, tej zaum nws yuav zoo dua los xaiv cov khoom siv ntxuav ntshav rau kev tso ntshav, vim tias kev tso ntshav ntawm cov khoom uas muaj ntshav plasma tuaj yeem ua rau muaj kev phom sij vim muaj cov neeg pub dawb IgM cov tshuaj tiv thaiv tiv thaiv T-antigen. Kev tshawb fawb ntxiv ntawm cov xwm txheej zoo li no txhawm rau tshawb xyuas kev nyab xeeb thiab kev kho mob zoo dua yuav xav tau yav tom ntej.

Ntau qhov kev txwv cuam tshuam nrog kev tshawb fawb tam sim no hais txog. Peb tsis tau txais cov ntaub ntawv tseem ceeb hauv chav kuaj mob hauv cov kab mob hnyav, xws li disintegrin-zoo li thiab metalloproteinase nrog thrombospondin hom 1 motif 13 (ADAMTS13) kev ua, platelet-associated IgG qib, qib haptoglobin, thiab cov txiaj ntsig ntawm Coombs. Nws yuav tsum tau hais ntxiv tias peb tsis tuaj yeem tsim kom muaj kev kuaj pom tseeb ntawm TMA vim tsis muaj cov ntaub ntawv no. Txawm li cas los xij, peb ntsuas cov xwm txheej no txog peb xyoos tom qab tus kab mob pib, thiab tsis muaj qhov txo qis hauv ADAMTS13 kev ua ub no, thiab qib ntawm platelet-associated IgG nyob rau hauv cov ntaub ntawv siv. Thaum qhov kev kuaj Coombs tau zoo, tus neeg mob tsis muaj ntshav qab zib thaum lub sijhawm ntawd. Kev kuaj Coombs feem ntau yog qhov zoo rau cov neeg mob S. pneumoniae infection-induced TMA (9). Yog li ntawd, peb tau txiav txim siab tias qhov kev sim Coombs tuaj yeem dhau los ua qhov zoo hauv kev koom nrog Capnocyto-phage tus kab mob, thiab tus neeg mob qhov kev sim Coombs tau zoo tsis tu ncua txij li thaum. Hemolysis paub tias tshwm sim hauv kev koom tes nrog DIC, thiab muaj qhov ua tau tias peb tus neeg mob tau TMA nrog DIC, thiab nws lub raum puas yuav tsuas yog tshwm sim los ntawm sepsis-induced ATN.

Hauv kev xaus, peb ntsib tus neeg mob uas tsim AKI thaum lub sijhawm kawmCapnocytophagakab mob, nyob rau hauv uas lub raum biopsy pom tubulointerstitial raug mob nrog T-antigen raug. Cov ntaub ntawv no qhia tias kev raug mob tubulointerstitial tshwm sim los ntawm kev tsim tawm neuraminidase thiab ua rau T-antigen raug yog ib qho txheej txheem ntawmCapnocytophagakis tau tus kab mob AKI.

Cov kws sau ntawv hais tias lawv tsis muaj qhov tsis sib haum xeeb ntawm kev txaus siab (COI).

Kev lees paub

Peb ua tsaug rau Ms. Sachiko Iwama rau nws cov kws tshaj lij kev pabcuam nrog cov tshuaj ntsuam xyuas histological.

Cov ntaub ntawv

1. Tani N, Nakamura K, Sumida K, Suzuki M, Imaoka K, Shimono N. Ib qho kev tiv thaiv kab mob ntawmCapnocytophagaCanimorsus Infection Complexed los ntawm Secondary Thrombotic Microangiopathy thiab Disseminated Intravascular Coagulation. Intern Med 58: 3479- 3482, 2019.

2. Mulder AH, Gerlag PG, Verhoef LH, van den Wall Bake AW. Tom qab hemolytic uremic syndromecapnocytophagacanimorsus (DF-2) septicemia. Clin Nephrol 55: 167-170, 2001.

3. Finn M, Dale B, Isles C. Ceev faj tus dev! Ib tus mob zoo li thrombotic thrombocytopenic purpura txuam nrog Cap- nocytophaga canimorsus septicemia. Nephrol Dial Transplant 11: 1839-1840, 1996.

4. Tobe TJ, Franssen CF, Zijlstra JG, de Jong PE, Stegeman CA. Ib qho hemolytic uremic syndrome vim yogCapnocytophagacanimorsus bacteremia tom qab aub tom. Am J Raum Dis 33: e5, 1999.

5. von Vigier RO, Seibel K, Bianchetti MG. Kev kuaj pom zoo Coombs hauv pneumococcus-associated hemolytic uremic syndrome. Kev tshuaj xyuas cov ntaub ntawv. Nephron 82: 183-184, 1999.

6. Veesenmeyer AF, Edmonson MB. Trends hauv US tsev kho mob nyob rau Streptococcus pneumonia-associated hemolytic uremic syndrome. Pediatr Infect Dis J 32: 731-735, 2013.

7. Moncla BJ, Braham P, Hillier SL. Sialidase (neuraminidase) kev ua haujlwm ntawm cov kab mob gram-negative anaerobic thiab capnophilic. J Clin Microbiol 28: 422-425, 1990.

8. Mally M, Shin H, Paroz C, Landmann R, Cornelis GR.Capnocytophagacanimorsus: ib tug tib neeg kab mob noj nyob rau saum npoo ntawm epithelial hlwb thiab phagocytes. PLoS Pathog 4: e1000164, 2008.

9. Shimizu M, Yokoyama T, Sakashita N, et al. Thomsen- Friedenreich antigen raug raws li qhov ua rau ntawm Streptococcus pyogenes-associated hemolytic-uremic syndrome. Clin Nephrol 78: 328-331, 2012.

10. Uchida T, Oda T. Glomerular Deposition of Nephritis-Associated Plasmin Receptor (NAPlr) and Related Plasmin Activity: Key Diagnostic Biomarkers of Bacterial Infection-related Glomeru- nephritis. Int J Mol Sci 21: 2595, 2020.

11. Alon U, Adler SP, Chan JC. Hemolytic-uremic syndrome txuam nrog Streptococcus pneumonia. Tshaj tawm ntawm rooj plaub thiab tshuaj xyuas cov ntaub ntawv. Am J Dis Child 138: 496-499, 1984.