4j87 FILE COPY Kidnry (I990)- PP 1Sh-1S" Lacrannond regulatory system for soluble immune response suppressor 3 production in steroid-responsive nephrotic syndrome 1 WILLIAM SCHNAPER of Padiatrics. UC Mrdicin . St. Louls. KalARIon Unlrrin Schoal Nbinun 1 Tha Edwrard Melllnckrodi Wrpanmgni culture  without requining actvation by SIRS cxorenous Lubk orodor mutcm [Ot 5utrtoz Panenirewith 5 WTTun circulating lymphocyics are ton Dcpbrolc Bxndrott- nephouc agcnts . suegcsting ntacanau Ichtaled prcvouse b Yndromt frequenuly mnve {uppTEEtE0 Lmmunc Tcponst $ the souice of SIRS body duids. This may bc accountcd for by with xtcroid mxponuvi suhiccu ncptouc Voeaed (lerinc thut_scce Irom_paticnts SRNS obscralon utn AchIIC producc Uc lymphokinc _ solubla immung rcsponte Endrome (SRNS SIRS SIRS production itsclf potentinl nornal Fmonocyes produce superseol Mee prteni cipcnncnis lerun SLRS disappears from body be]stcrui [-scnsitive inycuratcu. ITom SRRIS Son RcNyATOn muy dct nhlienis Hlh umulatcd nora hympnocytc: prouLcc nuids shortly aher Initinton stcroid Lhcrpy- In vLro sludies SIRS SIRS-inducing ecuvity Enuin Ircnimenl #oth Fcal aorocmt SIRS by uclivuled lymphocytes have shown that sccnclon hoilin nol nHeclcdby diyes acidincquon prolcinasc slercids. Howcvcr. block$ hudrocoriaone nrevenied hcalng 36 C hi: #cnim fncior could cetan nintnen produce SIRS by paticnl activation of supprcssor cels (IFNIa " scnuma Tuncuonmly und anurcncully Ironi SiR- nhdnromaneneron concanavalin IFN~ Suparlont cullund Palicni phocyics cnnched tOrCl SIRS -inducing such olher aecnts cc]s *crt Dsofound nctvnic normz lymphocyics producc Jate Taken (Oecther. these SuBBCEI the cxislcnce intcncronsi0l SIRS ymoitele-uchye Acuvu inoteduminr cnamcientucr by which suppressor cclls SRNS mtchuniam rcewlaton those Molecul wcuhe actons rerumt JuCLOT producc SIRS. mivahe ucnvncd ctimalcd JA. Iauu dnltont Rclnlruon Chrmalomu- belween slemoid-scnsitive SIRS pro- ernimAnd lvmdhocvic Aumrmalane [rom Ihe umc HuemcuuII sukne comcluuon ienla cluled 4lh *imilar Dallctns On Tcycucu-phuto Caaa Emna sicroid rcsponsivcnces of albuminune SUEESsts thal duclon anc SIRS inducing Iudctt senm ACEY acnccn dclincation thesc phcnomena common orein (6]. Thus have supprcttor-Induccr lymp OCe mnoranaicalcche pnencc rTuLu SIRS production might nlso provide ol Lhc events wbich Icad SIRS pruduction mechanixt sicroid-Tcsponsive ncnhroto the pathogencsis of prolcinurin rclaung nnlicot umomnwuor phrotic paticnls papcr , thc SIRS-inducing activ- pneten ity in thc scrum o[ ncphrolic paticnts is further charuclerized. 13,080 to 18,000 dalton prolcin nesulls Trom pregence 0 suppressed The close immune responsivcncss nesocintion #hich can distinguished from other subslanccs Dretiovuy wilh changc ncphrotic occuncncc minim& andromc SIRS ucuvale supprESSOT dclerninco cCS produce (MCNS) hns suegcstcd thnl thc immunological and renal abnor- CD Lymphocyte of thrs  Iactor lecly ~ourcc prc'cnt this Pathogenesi: (I): muinics condhuion hive thc PBMC of paticnts with stcroid-Iesponsive MCNS: EuTU uone Although progrcss bccn idcntifyinz madc numcrous These findings dafine pathway [or SIRS Tculalor produC charctcrizing delects ol Immnune quncuon anecad - risc  Uhc]possibilily thul   suppressed imunity nism of albuminuna [2]. thc cousc(s) of thesc phcnomcna presence nephrotic paticnts may rcsul. Ieast in pan , (rom thc Wc havc detcrmincd that unnc and scNum KOWIa prcviously population of cclls nclivaled sunprcstor-induccr cclla and Rom nlubi cermn nennrouc palienin naan uhnmuine SIRS: that rcspond Lhc inducer popuhuon producina sponse suppressor (SIRS) (3] . an antigen-nonspecific SuppTC> " that inhibits antibody vitro [4]. Iymphoxinc production Method antibody production dclaycd-type hypersensitivity Unlcss othertise specified. ul chemicals were reagent pade vivo [S}. Evdluution of nephrolic TceDontet epccrum purchascd {rom commcrcinl SOLCC 5 paticnls indicated thar SIRS was produccd by all Daticnti Who nephrosis and responded cunlicuelenond Inerny Palleni ponulalon (PBMC! from Pennhcr nlood mononuclon ccll DAuc nts Clinical malenuls were obtained from patients with MCNS or (SRNS} sectctc 4u stcroid-responsyc nephrouc syndromc histopathologic 42) undcr ol thc Renal Torn" UANAn an Iwisions o Childrcn Hospital . Bamc ; HosElLal . Lnc Jcy - Wushinglon University School Hospiln LouTS Mcdicine . Diagnosis WAs cstablished by rcnal biopsy cacedlin ~civcu [or publiculion Auinl 19 J9r8 1982 children whom   clinicul Tetuned Tom Rovembcr Cctnin nrcd Seven publicalion Janunly 1990 presumptive dingnosis ot MCNS Accepicthor scrologic crtcra indicalcd 1930 by the Intemnational Socicty of Ncphrology bring classificd stcroid-responsive Ducnc 151 PUBLICATIONS 034135
1Sh-1S" 4j87 Kidnry Lacrannond (I990)- PP FILE COPY regulatory system for soluble immune response suppressor 3 production in steroid-responsive nephrotic syndrome WILLIAM SCHNAPER 1 Wrpanmgni of Padiatrics. KalARIon Unlrrin Schoal Mrdicin . St. Louls. Nbinun UC Tha Edwrard Melllnckrodi 1 mutcm [Ot Lubk WTTun orodor SIRS culture  without requining actvation by cxorenous ton 5utrtoz ntacanau Dcpbrolc Bxndrott- Panenirewith 5 nephouc agcnts . suegcsting Ichtaled circulating lymphocyics are b Yndromt frequenuly mnve {uppTEEtE0 Lmmunc Tcponst $ prcvouse suhiccu with xtcroid mxponuvi ncptouc the souice of SIRS body duids. This may bc accountcd for by Voeaed (lerinc Endrome (SRNS obscralon thut_scce Irom_paticnts utn SRNS AchIIC producc Uc lymphokinc _ solubla immung rcsponte superseol Mee prteni lerun cipcnncnis potentinl nornal Fmonocyes produce SIRS SIRS production itsclf RcNyATOn inycuratcu. ITom muy be]stcrui [-scnsitive dct SLRS disappears from body nhlienis Hlh SRRIS Son umulatcd nora hympnocytc: prouLcc nuids shortly aher Initinton stcroid Lhcrpy- In vLro sludies SIRS Enuin SIRS-inducing ecuvity Fcal aorocmt Ircnimenl #oth hoilin nol nHeclcdby diyes acidincquon have shown that sccnclon SIRS by uclivuled lymphocytes prolcinasc hcalng 36 C hi: #cnim fncior could cetan nintnen nrevenied slercids. Howcvcr. hudrocoriaone block$ Tuncuonmly und anurcncully Ironi SiR- nhdnromaneneron (IFNIa " activation of supprcssor cels produce SIRS by paticnl scnuma IFN~ Suparlont cullund Palicni phocyics cnnched tOrCl olher SIRS -inducing aecnts such concanavalin cc]s *crt Dsofound nctvnic normz lymphocyics producc intcncronsi0l Taken (Oecther. these Jate SIRS SuBBCEI the cxislcnce ymoitele-uchye Acuvu inoteduminr cnamcientucr those Molecul wcuhe actons SRNS rcewlaton mtchuniam rerumt JuCLOT by which suppressor cclls ctimalcd JA. Iauu dnltont Rclnlruon Chrmalomu- mivahe ucnvncd producc SIRS. HuemcuuII ernimAnd lvmdhocvic Aumrmalane [rom Ihe umc sukne comcluuon belween slemoid-scnsitive SIRS pro- ienla cluled 4lh *imilar Dallctns On Tcycucu-phuto Caaa Emna duclon anc sicroid rcsponsivcnces of albuminune SUEESsts thal Iudctt senm SIRS inducing ACEY acnccn thesc phcnomena have common orein (6]. Thus dclincation supprcttor-Induccr lymp OCe mnoranaicalcche pnencc rTuLu mechanixt SIRS pruduction sicroid-Tcsponsive ncnhroto ol Lhc events wbich Icad SIRS production might nlso provide nnlicot umomnwuor rclaung the pathogencsis of prolcinurin phrotic paticnls pneten papcr , thc SIRS-inducing activ- ity in thc scrum o[ ncphrolic paticnts is further charuclerized. nesulls Trom pregence 0 13,080 to 18,000 dalton prolcin The close nesocintion suppressed immune responsivcncss #hich can distinguished from other subslanccs Dretiovuy wilh occuncncc minim& changc ncphrotic andromc dclerninco ucuvale supprESSOT cCS produce SIRS (MCNS) hns suegcstcd thnl thc immunological and renal abnor- lecly ~ourcc of thrs  Iactor CD Lymphocyte prc'cnt muinics this condhuion hive EuTU Pathogenesi: (I): uone thc PBMC of paticnts with stcroid-Iesponsive MCNS: Although progrcss bccn madc idcntifyinz numcrous These findings dafine Tculalor pathway [or SIRS produC delects ol Immnune quncuon charctcrizing anecad - risc  Uhc]possibilily thul   suppressed imunity nism of albuminuna [2]. thc cousc(s) of thesc phcnomcna nephrotic paticnts may rcsul. Ieast in pan , (rom thc presence KOWIa Wc havc prcviously detcrmincd that unnc and scNum nclivaled sunprcstor-induccr cclla and population of cclls Rom cermn nennrouc palienin naan nlubi uhnmuine that rcspond Lhc inducer popuhuon producina SIRS: sponse suppressor (SIRS) (3] . an antigen-nonspecific SuppTC> " Iymphoxinc that inhibits antibody production vitro [4]. Method antibody production dclaycd-type hypersensitivity Unlcss othertise specified. ul chemicals were reagent pade TceDontet vivo [S}. Evdluution epccrum of nephrolic purchascd {rom commcrcinl paticnls indicated thar SIRS was Daticnti Who SOLCC 5 produccd by all nephrosis and responded cunlicuelenond Inerny Palleni ponulalon Pennhcr nlood mononuclon ccll (PBMC! from DAuc nts 4u stcroid-responsyc nephrouc syndromc (SRNS} sectctc Clinical malenuls were obtained from patients with MCNS or histopathologic UANAn Torn" 42) undcr an ol thc Renal Iwisions o Childrcn Hospital . Bamc ; HosElLal . Lnc Jcy - Hospiln LouTS Wushinglon University School ~civcu [or publiculion Auinl 19 J9r8 Mcdicine . Diagnosis WAs cstablished by rcnal biopsy cacedlin Tetuned Tom Rovembcr 1982 Cctnin children nrcd Seven whom   clinicul Accepicthor publicalion Janunly 1990 scrologic crtcra indicalcd presumptive dingnosis ot MCNS 1930 by the Intemnational Socicty of Ncphrology Ducnc classificd bring stcroid-responsive 151 PUBLICATIONS 034135