Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

ANTI PRE-ECLAMPSIA VACCINE CONCEPT

Erry Gumilar Dachlan INTRODUCTION The variable an cla%%ic ar$icle &a$here c!m"le# ma$ernal i%$urbance% $ha$ are cau%e by $he "re&nancy%"eci'ic i%!r er !' "reeclam"%ia e'ie e#"lana$i!n un$il ()*)+ ,hen R!ber$% e$ al( in $heir $he evi ence $! inv!-e ac$iva$i!n !' ma$ernal en !$helium a% an un erlyin& "r!ce%%. Generali/e ma$ernal en !$helial cell y%'unc$i!n all!,e m!%$+ i' n!$ all+ clinical a%"ec$% $! be "!$en$ially e#"laine by a %in&le+ uni'yin& "r!ce%%0 hy"er$en%i!n $hr!u&h i%$urbe en !$helial c!n$r!l !' va%cular $!ne+ 'lui cl!$$in& be a%cribe re$en$i!n by increa%e en !$helial "ermeabili$y+ an y%'unc$i!n re%ul$in& 'r!m abn!rmal en !$helial e#"re%%i!n !' $! '!cal cerebral i%chemia re%ul$in& 'r!m

"r!c!a&ulan$. Eclam"%ia c!ul

va%!c!n%$ric$i!n+ c!n%i%$en$ ,i$h $he evi ence !' chan&e% e$ec$e by ne, cerebral ima&in& $echni1ue%. The liver y%'unc$i!n in$rin%ic $! $he 2ELLP 3hem!ly%i%+ eleva$e liver en/yme%+ an l!, "la$ele$ c!un$4 %yn r!me c!ul al%! be a$$ribu$able $! $he e''ec$% !' acu$e un er"er'u%i!n. Abun an$ evi ence ,a% &a$here in %u""!r$ !' $he "r!"!%al+ an ne, a$a have %ince rein'!rce $he ini$ial e%cri"$i!n. A% ,i$h all &!! a vance% in "erce"$i!n+ 'ur$her ,!r- ha% been %$imula$e + an much !' $hi% ,!r- ha% '!cu%e !n i en$i'yin& $he 'ac$!r% $ha$ c!ul cau%e $he en !$helial i%$urbance%. En !$helial cell% can be ac$iva$e in %everal i''eren$ ,ay% $ha$ are "!$en$ially relevan$ $! $he !ri&in% !' "reeclam"%ia+ an %everal can i a$e 'ac$!r% have emer&e + inclu in& 'ree 'a$$y aci %+ li"!"r!$ein%+ !#i i/e li"!"r!$ein% !r li"i "er!#i e%+ $um!r necr!%i% 'ac$!r+ 'ibr!nec$in e&ra a$i!n "r! uc$%+ an c!ur%e !' $he i%ea%e. The %!urce !' $he 'ac$!r% $ha$ lea $! en !$helial cell y%'unc$i!n ha% n!$ been e$ermine ,i$h cer$ain$y+ bu$ $he evi ence "!in$% $! $he "lacen$a. The ar&umen$% are ,ell rehear%e an e"en !n $he 'ac$ $ha$ "lacen$al $i%%ue i% e%%en$ial $! &enera$e $he en %$a&e% !' $he clinical %yn r!me !' "reeclam"%ia. 5ur$herm!re+ in $he rare circum%$ance !' e#$rau$erine "re&nancy+ in ,hich elivery !' $he 'e$u% !e% n!$ lea $! elivery !' $he "lacen$a+ %i&n% !' $he i%ea%e "er%i%$ "!%$ "ar$um in%$ea !' remi$$in&. I$ %h!ul be em"ha%i/e $ha$ $he im"!r$ance !' $he "lacen$a e"!r$e %yncy$i!$r!"h!bla%$ic micr!vill!u% 'ra&men$%. A$ "re%en$

$here i% n! e'ini$e rea%!n $! %u""!%e $ha$ $here mu%$ be !nly a %in&le 'ac$!r !"era$in& urin& $he

Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

rela$e% !nly $! $he en -%$a&e i%ea%e urin& $he %ec!n hal' !' &e%$a$i!n. The 'ac$!r% $ha$ lea $! "!!r "lacen$a$i!n a "u$a$ive "recur%!r $! $he "reeclam"%ia %yn r!me are %e"ara$e an n!$ irec$ly relevan$ $! $hi% ar&umen$.
The cen$ral r!le !' $he "lacen$a in $he "a$h!&ene%i% !' "re-eclam"%ia i% un i%"u$e . The evi ence $ha$ ma$ernal %yn r!me !' "re-eclam"%ia i% cau%e by a ma$ernal %y%$emic in'lamma$!ry re%"!n%e 3MSIR4 i% revie,e . The "!lym!r"hic na$ure !' $he in'lamma$!ry ne$,!r- e#"lain% $he iver%i$y !' $he varie %i&n% !' $hi% c!n i$i!n. A -ey !b%erva$i!n i% $ha$ an MSIR i% al%! a 'ea$ure !' n!rmal $hir $rime%$er "re&nancy+ bu$ le%% %evere $han in "re-eclam"%ia. 2ence "re-eclam"%ia i% %im"ly $he e#$reme en !' a c!n$inuum c!mm!n $! all "re&nancie%+ ,i$h mul$i"le c!n$ribu$in& 'ac$!r%. Evi ence i% "re%en$e $ha$ a"!"$!$ic !r necr!$ic ebri% %he 'r!m $he %yncy$ial %ur'ace !' $he "lacen$a c!n%$i$u$e% $he in'lamma$!ry %$imulu% in all "re&nancie%. Thi% m! el e#"lain% many 'ea$ure% !' "re-eclam"%ia inclu in& i$% !ccurrence ,i$h ei$her lar&er "lacen$ae !r %mall !#i a$ively %$re%%e "lacen$ae. The clinical im"lica$i!n% are $ha$ in $erm% !' ia&n!%i% !r "re ic$i!n $here can never be a clear i%$inc$i!n be$,een n!rmal an abn!rmal. N! $e%$+ "re ic$ive !r ia&n!%$ic+ can be e#"ec$e $! i%$in&ui%h ab%!lu$ely be$,een i''eren$ e&ree% !' a "r!blem $ha$ i% c!mm!n $! all "re&nancie%. The "!%%ibili$y $ha$ $he MSIR a%%!cia$e ,i$h $hir $rime%$er "re&nancy i% n!$hin& m!re $han $he ma$ernal "rice '!r %u%$ainin& &e%$a$i!n i% c!n%i ere . In%ulin re%i%$ance i% a 'ea$ure !' n!rmal "re&nancy an al%! !' %y%$emic in'lamma$!ry %$a$e% in n!n-"re&nan$ in ivi ual%. I$ ha% been "revi!u%ly "r!"!%e $ha$ $he in%ulin re%i%$ance !' "re&nancy i% an im"!r$an$ a a"$a$i!n $! iver$ ma$ernal &luc!%e $! mee$ $he nee % !' $he '!e$u%. 2ence $he MSIR+ by cau%in& ma$ernal in%ulin re%i%$ance+ may have %ub%$an$ial '!e$al a van$a&e% %! l!n& a% i$ i% n!$ $!! %evere.

ANTI PRE-ECLAMPSIA VACCINE CONCEPT The i en$i'ica$i!n !' "e"$i e% rec!&ni/e by human $um!r-%"eci'ic CTL%+ an $he cl!nin& !' &ene% $ha$ enc! e $um!r-%"eci'ic an$i&en% rec!&ni/e by CTL%+ e%cribe earlier+ ha% "r!vi e $he ba%i% '!r an!$her '!rm !' ac$ive an$i-$um!r immuni /a$i!n+ namely $he in$r! uc$i!n !' %"eci'ic $um!r an$i&en% in$! $um!r-bearin& "a$ien$% u%in& immu n!&enic vaccine "re"ara$i!n%. The ra$i!nale '!r $hi% 6$hera"eu$ic6 vaccine a""r!ach i% $he li-eli h!! $ha$ $he $um!r-%"eci'ic mem!ry T cell% in $um!r "a$ien$% c!ul be ac$ively an %"eci'ically %$imula$e by %uch vaccine%+ an 'ur$her evel!"men$ !' mem!ry T cell% c!ul be enhance . Immuni/a$i!n ,i$h $he%e an$i&en% can be $he!re$ically acc!m"li%he by irec$ a mini%$ra$i!n !' "uri'ie "e"$i e !r "r!$ein+ by immuni/a$i!n ,i$h cell% e#"re%%in&

Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

rec!mbinan$ &ene% ,hich enc! e $he%e an$i&en%+ !r by in8ec$i!n !' e#"re%%i!n vec$!r% en c! in& $um!r an$i&en% 3DNA vaccine%4. The an$i "re-eclam"%ia vaccine c!nce"$ ba%e !n $he "re%ence !' an$i-en !$helial cell an$ib! ie% ,hich ma-e $he va%cular en !$helial cell% im"!r$an$ immun!l!&ic $ar&e$%. They e#"re%% a varie$y !' an$i&en% !n ,hich ac$iva$i!n !' $he en !$helium by cy$!-ine %uch a% in$er'er!n-9+ ,hich are &enera$e been e%cribe urin& cell me ia$e immune re%"!n%e%+ can lea au&men$a$i!n i%!r er an are believe $! "lay a r!le in $he ,he$her !' an$i&en e#"re%%i!n an in uc$i!n !' ne!an$i&en. An$ib! ie% $! va%cular en !$helium have in a varie$y !' va%culi$ic "a$h!&ene%i% !' $he%e% i%ea%e%. :he$her an$i-en !$helial cell an$ib! ie% are "re%en$ in "re-eclam"%ia an an$ib! y ac$ivi$y c!rrela$e% ,i$h any !' $he clinical !r lab!ra$!ry mani'e%$a$i!n !' $he i%ea%e+ Ra""a"!r$ an c!,!r-er% ,i$h $he ELISA 3En/yme-lin- immun!%!rben$ a%%ay4 u%e em!n%$ra$e increa%e bin in& !' immun!&l!bulin G $! human umbilical vein en !$helial cell% by %era 'r!m ,!men ,i$h %evere "re-eclam"%ia a% c!m"are ,i$h n!rmal "re&nan$ c!n$r!l ,!men. The!re$ically $he "ur"!%e !' $hi% an$i "re-eclam"%ia vaccine c!nce"$ $! e$ermine a% '!ll!,%0 (. Immun!'lu!re%cen$ %$u ie% !' an$i -en !$helial cell an$ib! ie% 3Aeca I&G4 T! %h!, bin in& !' I&G $! n!rmal $i%%ue !n ,hich renal c!r$e# $i%%ue ,a% nee e can be available by renal immun!'lu!re%cen$ %$ainin&. N!rmal renal c!r$ical $i%%ue ,a% !b$aine 'r!m ,e &e bi!"%y %"ecimen% !' "a$ien$% ,h! un er,en$ renal bi!"%y '!r clinical in ica$i!n%.

7. Pla%ma an$i-en !$helial cell an$ib! ie% 3Aeca I&G4 !' ,!men ,i$h "re-eclam"%ia The I&G 'rac$i!n ,a% i%!la$e 'r!m $he "!!le "la%ma !' "re-eclam"%ia ,!men $! "re"are monoclonal anti human Aeca IgG antibody. ;. Inhibi$i!n !' an$i-en !$helial cell an$ib! ie% 3Aeca I&G4 The rec!&ni$i!n !' an$i&en by an$ib! y inv!lve% n!n-c!valen$ rever%ible bin in&. The %$ren&$h !' $he bin in& be$,een a %in&le an$ib! y c!mbinin& %i$e an a m!n!valen$ an$i&en+ ,hich can be e$ermine by e#"erimen$+ i% calle $he a''ini$y !' $he in$erac$i!n. The

Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

a''ini$y i% c!mm!nly re"re%en$e

by a

i%%!cia$i!n c!n%$an$ 3< 4+ ,hich

e%cribe% $he

c!ncen$ra$i!n !' an$i&en $ha$ i% re1uire $! !ccu"y !ne hal' !' $he an$ib! y-c!mbinin& %i$e% "re%en$ in a %!lu$i!n !' an$ib! y m!lecule%. A %maller < in ica$e% a %$r!n&er !r hi&her a''ini$y in$erac$i!n+ %ince a l!,er c!ncen$ra$i!n !' an$i&en i% nee e $! !ccu"y $he %i$e%. The e#$en$ !' $he increa%e in an$i&en in%i e $he membrane e"en % !n $he an$i&en

c!ncen$ra$i!n+ !n $he an$ib! y c!ncen$ra$i!n+ an !n $he < !' $he bin in& in$erac$i!n. =y mea%urin& $he an$i&en an an$ib! y c!ncen$ra$i!n by %"ec$r!%c!"y !r by $he !$her mean%+ $he < can be calcula$e .

>.

Mea%uremen$ !' an$i-en !$helial cell an$ib! ie% 3I&G4 ac$ivi$y En/yme immun!a%%ay u%e i% available $! mea%ure an$i-en !$helial cell an$ib! ie% 3I&G4 ac$ivi$y

?. Mea%uremen$ !' a he%i!n m!lecule% inclu e VCAM+ICAM an E-Selec$in ac$ivi$y. The%e a he%i!n m!lecule% ,hich have been %h!,n $! be eleva$e in $he "la%ma !' "reeclam"%ia ,!men are $he immun!&l!bulin %u"er'amily. I$ ,i ely 3'!r in%$ance VCAM-( i% a (@@ -il! al$!n "r!$ein4 i%$ribu$e in en !$helial+ e"i$helial+ macr!"ha&e+ an lym"h!cy$e%+ m!n!cy$e%+ an en ri$ic cell%. I$ i% im"!r$an$ '!r recrui$in& leuc!cy$e% $! %i$e% !' in'lamma$i!n becau%e i$ me ia$e% $he a he%i!n !' e!%in!"hil% $! en !$helium. The li&an % '!r VCAM-( are in$e&rin%. VCAM-( e#"re%%i!n !n en !$helial cell% i% in uce by IL-(A+ IL->+ TN5+ an I5N9. All $he%e a he%i!n m!lecule% are e$ermine ,i$h an ELISA $echni1ue.

A 8uvan$% an Immun!m! ula$!r%. The ini$ia$i!n !' T cell- e"en en$ immune re%"!n%e% a&ain%$ "r!$ein an$i&en% re1uire% $ha$ $he an$i&en% be a mini%$ere ,i$h a 8uvan$%. M!%$ a 8uvan$% in uce l!cal in'lamma$i!n+ ,i$h increa%e e#"re%%i!n !' c!%$imula$!r% an "r! uc$i!n !' cy$!-ine%+ %uch a% IL-(7+ $ha$ %$imula$e T cell &r!,$h an i''eren$ia$i!n. 2ea$--ille bac$eria are "!,er'ul a 8uvan$% $ha$ are c!mm!nly u%e in e#"erimen$al animal%. 2!,ever+ $he %evere l!cal in'lamma$i!n %uch a 8uvan$% $ri&&er "reclu e% $heir u%e in human%. Much e''!r$ i% curren$ly bein& ev!$e $! evel!"in& %a'e an e''ec$ive a 8uvan$% '!r u%e in human%. Several are in clinical "rac$ice+ inclu in& aluminum hy r!#i e &el 3,hich bin % "r!$ein% n!n-c!valen$ly an in uce% mil in'lamma$i!n4+ an li"i '!rmula$i!n% $ha$ are in&e%$e by "ha&!cy$e%. An al$erna$ive $! a 8uvan$% i% $! a mini%$er %ub%$ance%

>

Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

$ha$ %$imula$e T cell re%"!n%e% 3an ,hich are elici$e by $he a 8uvan$%4 $!&e$her ,i$h an$i&en%. 5!r in%$ance+ IL-(7 inc!r"!ra$e in vaccine% "r!m!$e% %$r!n& cell-me ia$e immuni$y an i% in early clinical $rial%. A% men$i!ne ab!ve+ i$ may be "!%%ible $! inc!r"!ra$e c!%$imula$!r% 3=B m!lecule%+ CD>@4 !r cy$!-ine% in$! "la%mi vaccine%+ u%in& rec!mbinan$ DNA $echn!l!&y.

Anti Pre-Eclampsia Vaccine Concept

erry gumilar dachlan

RE5ERENCES Abba% A<+ Lich$man A2 an P!ber CS+ ())B. Immuni$y in De'en%e an Di%ea%e.

Saun er% Te#$ an Revie, Serie% Cellular an M!lecular Immun!l!&y $hir e i$i!n+ ".;?)-D@. En re%en MCR+ M!rri% CM+ N!bre&a AC+ =uc-ley D+ e$ al. Serum 'r!m "reeclam"%ia ,!men in uce% va%cular cell a he%i!n m!lecule-( e#"re%%i!n !n human en !$helial cell% in vi$r!0 A "!%%ible r!le !' increa%e circula$in& level% !' 'ree 'a$$y aci %. Am C Ob%$e$ Gynec!l+ Se"$ember ())*+ V!l.(B)+ N!.;+ Par$ (+ ".DD?-B@. Peaceman AM an Rehnber& <A. The immun!&l!bulin G 'rac$i!n 'r!m "la%ma c!n$ainin& an$i"h!%"h!li"i an$ib! ie% cau%e% increa%e "lacen$al $hr!mb!#ane "r! uc$i!n. Am C Ob%$e$ Gynec!l December ())7+ V!l.(DB+ N!.D+ ". (?>;-B. Ra""a"!r$ VC+ 2ira$a G+ Ea" 2< an >B. C!r an SC. An$i-va%cular en !$helial cell

an$ib! ie% in %evere "reeclam"%ia. Am C Ob%$e$ Gynec!l+ Canuary ())@+ V!l.(D7+ N!.(+ ".(;*-