M E D iC A L
JO U R N A L
" '/ '~ , ', ' " , , '" , 4 ~
~ L ] N I C A : L
S C I E N C E
, h- : , . . ~ ,O U . I G I N A L
A . I ~ T I C L E
W a ld e n is e C o s s e rm e lli-M e s s in a W ils o n C o s s e rm e lli
H u m o r a l im m u n ity in H a n s e n 's D is e a s e
P a r t o f th e M a ster 's th esis. D ep a r tmen t o f Rh eu ma to lo g y/La b o r a to r y o f Rh eu ma to lo g y In
vesti-g a tio n - LIM -1 7 , o f th e U n iver sity H o sp ita l o f th e C o lleg e o f M ed icin e o f th e U n iver sid a d e d e
Sa o P a u lo . P a r tia lly fu n d ed b y th e F o u n d a tio n fo r th e D evelo p men t o f Rh eu ma to lo g y, Br a
zil-ia n So ciety o f Rh eu ma to lo g y (o th er fu n d s) a n d Sa n d o z La b o r a to r ies - Sa o P a u lo , Br a zil
F o r m a n y y e a r s im m u n e r e s p o n s e in le p r o s y h a s b e e n s tu d ie d . S in c e 1 9 6 0 s e v e r a l r e p o r ts d e a lin g w ith h u m o r a l im m u n ity h a v e b e e n d e s c r ib e d in th e lite r a tu r e . D iffe r e n t a u to a n tib o d y r a te s o c c u r in le p r o s y . T h e r e is a n in c r e a s e in th e p r e v a le n c e o f a u to a n tib o d ie s in e ld e r ly p a tie n ts w ith lo n g s ta n d in g d is e a s e , in le p r o m a to u s le p r o s y a n d in th o s e w ith r e a c tio n a l s ta te s . T h e d ife r e n c e s in r a te s a m o n g v a r io u s s tu d ie s a r e a ttr ib u te d to d iffe r e n t m e th o d s a n d v a r ia tio n s a m o n g p a tie n t s a m p le s c o n c e r n in g a g e , g e n d e r , p o la r fo r m s , th e r a p y a n d o th e r e le m e n ts . T h e p r e v a le n c e o f n u m e r o u s a n tib o d ie s , im m u n e c o m p le x e s , c r y o g lo b u lin s a n d c o m p le m e n t le v e ls h a v e b e e n s tu d ie d b y m a n y a u th o r s . T h is a ls o h ig h lig h ts th e im p o r ta n c e o f th e 'm o r e r e c e n t r e v ie w s o fa n ti-M y c o b a c te riu m le p ra e g ly c o lip id a n tib o d ie s s u c h a s th e a n ti- p h e n o lic g ly c o lip id - I a n tib o d ie s in w h ic h tite r s a r e v a r ia b le a n d d e p e n d o n g e n e tic fa c to r s .
U N IT E R M S : A n tib o d ie s . H a n s e n 's D is e a s e . Im m u n ity . C r y o g lo b u lin s . Im m u n e c o m p le x e s . C o m p le m e n t.
IN T R O D U C T IO N
T
h e a c t i v a t i o ni m m u n i t y h a so f b o t hb e e n d e t e c t e dh u m o r a l ( 4 6 ) a n d c e l l u l a ri n H a n s e n 's D i s e a s e( 7 1 ) ( 1 7 , 1 8 ) . E s p e c i a l l y i n t h e l e p r o m a t o u s f o r m , t h ep o l y c l o n a l a c t i v a t i o n o f B - c e l l s h a s b e e n k n o w n s i n c e t h e
1 9 6 0 's b y m e a n s o f a n t i b o d y d e t e c t i o n a n d s e r i c
h y p e r g a m m a g l o b u l i n e m i a a n d i s c o n s i d e r e d t o b e d u e t o
t h e c h r o n i c i t y o f t h e d i s e a s e . O n t h e o t h e r h a n d , s p e c i f i c
a n t i b o d i e s a g a i n s t t h e m y c o b a c t e r i a ( 0 3 , 3 1 , 4 4 ) , o t h e r
A d d re s s fo r c o rre s p o n d e n c e :
W a ld e n is e C o s s e rm e lli M e s s in a
Av . O r. A rn a ld o , 4 5 5 - 3Q a n d a r - R e u m a to lo g ia S a o P a u lo /S P - B ra s il. C E P 0 1 2 4 6 -9 0 3
m y c o b a c t e r i a l i m m u n o g l o b u l i n s ( 1 5 ) a n d a u t o a n t i b o d i e s
h a v e b e e n d e s c r i b e d ( 2 0 , 2 1 , 2 3 , 2 7 , 3 8 , 5 1 , 6 1 , 6 7 ) , a s i n o t h e r
i n f e c t i o u s d i s e a s e s ( 0 1 , 1 0 , 1 1 , 2 6 , 3 0 , 3 7 , 4 2 , 4 3 , 5 0 , 6 0 ) , a n d
a r e i m p o r t a n t f o r a n a l y s i s a n d d i a g n o s i s ( 5 7 , 5 8 , 6 5 ) .
S P E C IF IC A N T IB O D IE S
I n 1 9 8 2 , H u n t e r e t a l . ( 4 4 ) , c h e m i c a l l y d e s c r i b e d a
g l y c o l i p i d f r o m M yco b a cter iu m lep r a e c u l t i v a t e d i n
a r m a d i l l o s . L a t e r t h e s a m e s t r u c t u r e w a s f o u n d i n i n f e c t e d
h u m a n t i s s u e s . T h r o u g h e n z y m e - l i n k e d i m m u n o s o r b e n t
a s s a y ( E L I S A ) , i t w a s s h o w n t h a t t h e s e a n t i b o d i e s w e r e
s p e c i f i c t o th eM . lep r a e i n f e c t i o n ( 1 9 , 4 0 ) a n d t h a t p a t i e n t s
w i t h t u b e r c u l o s i s a n d o t h e r m y c o b a c t e r i a l i n f e c t i o n s d i d
n o t s h o w a n y r e a c t i o n t o t h i s a n t i g e n . T h e f a l s e - p o s i t i v e
r a t e w a s 3 % , a n d l e p r o m a t o u s p a t i e n t s p r e s e n t e d t h e m o s t
930
s ig n ific a n t ra te s o f th e s e a n tib o d ie s c a lle d a n ti-p h e n o lic g ly c o lip id -I a n tib o d ie s (a n ti-P G L -I) (8 4 ). D u e to th e lo w p re s e n c e o f le v e ls o f a n ti-P G L -I in p a tie n ts e x p o s e d to th e E L IS A te s t fo r th is a n tib o d y , is n o t c o s id e re d d ia g n o s tic (3 4 ) b u t h a s b e e n c o n s id e re d u s e fu l fo r e p id e m io lo g ic a l s tu d ie s , e s p e c ia lly in e n d e m ic a re a s (1 9 ,7 5 ) a n d p a tie n ts th a t h a v e b e e n in c o n ta c t w ith le p ro s y .
R e c e n t s tu d ie s h a v e s h o w n th a t th e s c o p e a n d m a g n itu d e o f a n tib o d ie s p ro d u c e d b y m ic e a g a in s t c e rta in m y c o b a c te ria l p ro te in s m a y v a ry g re a tly (1 6 ). In s tu d ie s w ith
M.leprae,
it is b e lie v e d th a t th e s e d iffe re n t re s p o n s e s a re in flu e n c e d b y . g e n e tic b a c k g ro u n d . A fte r in o c u la tin g m ic e w ithM.leprae
s o n ic a te a n d th e re c o m b in a n t 6 5 k D a p ro te in , d iffe re n c e s in th e n u m b e r a n d s tru c tu re o f th e re c o g n iz e d e p ito p e s w e re n o te d , a n d th e p a rtic ip a tio n o f n o n -H 2 g e n e s w a s d e m o n s tra te d (0 4 ).A U T O A N T I B O D I E S
A m o n g ra b b its , b a c te ria l im m u n iz a tio n c a u s e s d e v e lo p m e n t o f a n tig a m m a g lo b u lin s v e ry s im ila r to th e rh e u m a to id fa c to r (0 1 ). L a te , a n ti-D N A a n tib o d ie s m a y b e fo u n d a lo n g w ith p ro life ra tiv e g lo m e ru lo n e p h ritis d ia g n o s e d d u rin g a u to p s y (2 5 ). H o w e v e r, in H a n s e n 's D is e a s e , th e s o le p re s e n c e o f th e s e a n tib o d ie s h a s n o t b e e n re la te d to a n y s p e c ific c lin ic a l m a n ife s ta tio n , e x c e p t w h e n im m u n e c o m p le x d e p o s its o c c u r. In 1 9 6 6 , A z e v e d o a n d M e lo (0 6 ) re c o g n iz e d th a t th e d e c re a s e in c o m p le m e n t a c tiv a tio n in re a c tio n a l s ta te s o f le p ro s y is d u e to th e c o m p le m e n t b in d in g b y th e a n tig e n -a n tib o d y c o m p le x e s .
T h e a u to a n tib o d ie s in H a n s e n 's D is e a s e a p p e a r a t d iffe re n t ra te s th a t v a ry a c c o rd in g to th e p o p u la tio n s tu d ie d , to th e m e th o d s u s e d a n d to th e p e rio d in w h ic h th e y w e re c a rrie d o u t. A lth o u g h s o m e s tu d y g ro u p s h a v e s h o w n a h ig h e r p re v a le n c e o f H a n s e n 's D is e a s e th a n in th e c o n tro l g ro u p s (6 2 ), s e v e ra l a u to a n tib o d ie s h a v e b e e n id e n tifie d , a m o n g th e m a n ti-n u c le a r fa c to rs (1 1 ,1 4 ,5 4 ,6 4 ,8 2 ), rh e u m a to id fa c to rs (2 1 ,4 2 ,6 4 ,6 7 ,8 2 ), a n ti-tire o g lo b u lin (1 2 ,5 2 ,6 4 ,8 2 ), a n ti-s m o o th m u s c le , a n ti-c a rd io lip in (2 8 ,3 6 ,3 9 ,7 9 ), a n ti-c o lla g e n I a n d II (5 3 ), a s w e ll a s fa ls e p o s itiv e s y p h ilis re a c tio n s (3 5 ,5 2 ), th a t m a y in d ic a te th e p re s e n c e o f a n ti-p h o s p h o lip id a n tib o d ie s a n d /o r a c ro s s -re a c tio n w ith th e m y c o b a c te ria l a n tig e n ic c o m p o n e n ts .
T h e p ro d u c tio n o f a n tib o d ie s is m o re c h a ra c te ris tic o f th e le p ro m a to u s fo rm (2 3 ,5 2 ,6 4 ), d e m o n s tra te d b y h ig h tite rs o f g a m m a g lo b u lin (0 2 ,0 3 ,7 3 ) e s p e c ia lly in th e re a c tio n a l s ta te s , a n d c a n b e d e te c te d a ls o in p a tie n ts in d is e a s e re m is s io n (8 2 ). A n in v e rs e re la tio n b e tw e e n th e
a n tib o d y a n d th e c e lu la r re a c tio n s h a s a ls o b e e n s u g g e s te d (6 3 ). L o n g d u ra tio n o f d is e a s e , o ld a g e , a n d a h is to ry o f re c c u rrin g e rith e m a n o d o s u m le p ro s u m (E N L ) p re d is p o s e th e fo rm a tio n o f a u to a n tib o d ie s in th e s e p a tie n ts (6 3 ).
In s e v e ra l s tu d ie s (0 5 ,1 4 ,2 0 ,2 1 ,2 3 ,4 7 ,5 2 ,6 4 ,6 6 ,6 8 ). th e d e te c tio n o f th e rh e u m a to id fa c to r ra n g e s fro m z e ro (5 5 ) to 1 0 0 % (2 8 ). S in c e th e la te x fix a tio n te s t is m o re s e n s itiv e a n d le s s s p e c ific th a n th e W a a le r-R o s e te s t, it c a n b e a s s u m e d th a t th is s e n s itiv ity c o u ld c o n trib u te to th e s e d iffe re n c e s in ra te . In a d d itio n , in s tu d ie s w h e re th e ra te s a re v e ry h ig h , th e n u m b e r o f p a tie n ts s tu d ie d is lo w (0 8 ). T h e id e n tific a tio n o f s e n c rh e u m a to id fa c to r in le p ro s y p a tie n ts o c c u rs b o th in tu b e rc u lo id a n d le p ro m a to u s fo rm s , a lth o u g h w ith a h ig h e r in c id e n c e in th e la tte r (6 4 ). A c c o rd in g to P e c h c la i e t a l.. (6 4 ), rh e u m a to id fa c to r tite rs c a n b e lo w , d e p e n d in g o n th e p o p u la tio n c h o s e n . In h o s p ita liz e d p a tie n ts tite rs u p to
1 :5 1 2 0 w e re fo u n d (2 1 ).
T h e p ro d u c tio n o f s e ric fa c to rs v e ry s im ila r to rh e u m a to id fa c to r c a n b e s tim u la te d b y m ic ro o rg a n is m s (ra b b it h y p e rim m u n iz a tio n w ith
Escherichia
coli
a n dBacillus
subtilis)
(0I ) . N o c o rre la tio n w a s fo u n d w ith a rth ritis o r rh e u m a to id d is e a s e in th e s e s u b je c ts . It is k n o w n th a t rh e u m a to id fa c to rs w e re a ls o d e te c te d in in fe c tio n s s u c h a s tu b e rc u lo s is (8 3 ) a n d s y p h ilis (6 0 ).A n tin u c le a r fa c to rs a n d L .E . c e lls w e re s tu d ie d in le p ro s y p a tie n ts a s a n a tte m p t to d ia g n o s e a p o s s ib le a s s o c ia tio n w ith c o n n e c tiv e tis s u e d is e a s e s (7 4 ), s in c e jo in t a n d s k in m a n ife s ta tio n s m a y m im ic s e v e ra l rh e u m a tic s y m p to n s . S im ila ry to rh e u m a to id fa c to r, th e ra te s fo u n d (0 8 ,2 3 ,4 7 ) v a rie d g re a tly , ra n g in g fro m z e ro (5 5 ) to 2 9 % (1 4 ,6 3 ). A lth o u g h L .E . c e lls h a v e b e e n fo u n d (1 4 ,4 7 ,5 2 ) a n d le p ro s y p a tie n ts w ith lu p o id a s p e c ts h a v e b e e n re p o rte d (1 2 ) th e a s s o c ia tio n w ith s y s te m ic lu p u s e ry th e m a to s u s w a s n o t s ig n ific a n t.
A u to a n tib o d ie s re a c tiv e to n a tiv e o r d e n a tu re d c o lla g e n ty p e II w e re d e te c te d in th e s e ru m o f 1 1 o u t o f 2 0 p a tie n ts w ith th e le p ro m a to u s fo rm in w h ic h a n tib o d y le v e ls w e re s ig n ific a n tly h ig h e r th a n th o s e w ith rh e u m a to id d is e a s e ; h o w e v e r, n o n e o f th e s e p a tie n ts h a d a n y s ig n s o f a rth ritis (2 4 ).
C I R C U L A T I N G I M M U N E C O M P L E X E S ( 2 2 , 6 9 , 7 0 , 8 5 ) ,
C R Y O G L O B U L I N S ( 5 2 ) A N D C O M P L E M E N T ( 2 2 )
A lth o u g h th e p re s e n c e o f a u to a n tib o d ie s d o e s n o t a lw a y s m e a n p a th o g e n ic ity , th e p re s e n c e o f im m u n e c o m p le x e s in th e tis s u e s d o e s s u g g e s t s o m e p a rtic ip a tio n in c lin ic a l m a n ife s ta tio n s (8 6 )
S a o P a u lo M e d ic a l J o u r n a l/ R P M 1 1 3 ( 4 ) : 9 2 9 - 9 3 4 , 1 9 9 5
931
T h e p eriv ascu lar im m u n e co m p lex es seen in th e
d erm is, an d b o u n d to so lu b le m y co b acterial an tig en s w ere
d etected in p atien ts w ith E N L , su g g estin g a p o ssib le ro le
in its p ath o g en esis (5 6 ). Im m u n e co m p lex es h av e also b een
d em o n strated in ren al b io p sies o f lep ro sy p atien ts (3 2 ) an d
related to a d ecrease in co m p lem en t in th ese p atien ts (0 9 ).
P atien ts w ith b o rd erlin e lep ro sy in reactio n sh o w ed
circu latin g im m u n e co m p lex es (Ig G an d th e C 3 fractio n ),
w h ile in lep ro m ato u s lep ro sy im m u n e co m p lex es w ere
fo rm ed b y rh eu m ato id facto r an d Ig M , esp ecially in th o se
p atien ts w ith arth ritis (5 9 ), an ti-m y co b acterial an tib o d ies
an d cry o g lo b u lin s (1 3 ).
B y u sin g th e C 1 q reactio n m eth o d , im m u n e
co m p lex es w ere also id en tified in th e seru m o f th e p atien ts
w ith th e tu b ercu lo id fo rm , in co n trast to p rev io u s stu d ies
th at sh o w ed elev ated im m u n eco m p lex es o n ly d u rin g E N L
R eactio n (7 2 ). S ev en ty p ercen t o f th e p atien ts w ith th e
lep ro m ato u s fo rm stu d ied b y R o jas-E sp in o sa et al.. (7 2 )
an d 7 6 % o f th e p atien ts stu d ied b y M o ran et al.. (5 6 )
sh o w ed circu latin g im m u n e co m p lex es w h en th e sam e
m eth o d w as em p lo y ed .
C o m p lem en t d etectio n m ay b e u sefu l to th e d iag n o sis
o f H an sen 's D isease (4 8 ,7 6 ,7 7 ,8 1 ). H ig h lev els o f
co m p lem en t, esp ecially o f th e C 2 an d C 3 co m p o n en ts (3 3 )
d u rin g E N L ep iso d es h av e b een rep o rted (7 8 ). T iters o f
co m p lem en t in th e sy n o v ial flu id m ay h av e a p ractical
sig n ifican ce w h en co m p ared to b lo o d lev els (4 9 ).
C ry o g lo b u lin em ia m ay cau se sev ere co m p licatio n s
su ch as p ro liferativ e g lo m eru lo n ep h ritis w ith lin ear Ig G
an d Ig M d ep o sits an d g ran u lar d ep o sits o f C 3 (4 5 ). A h ig h
freq u en cy s w as o b serv ed d u rin g E N L , in p atien ts
u n d erg o in g treatm en t (5 8 % ) an d in u n treated p atien ts w ith
E N L (5 2 ). A ll six p atien ts assessed b y B o n o m o (1 3 )
p resen ted m ix ed cry o g lo b u lin s an d Ig G an d fiv e h av e
p o ly clo n al Ig M , w ith o n e Ig M p resen tin g o n ly lig h t-ch ain
k ap p a.
A lth o u g h it is g en erally ag reed th at co m p eten t
im m u n ity fo r b acillar d estru ctio n is m ed iated b y an
efficien t T -cell resp o n se, so m e au th o rs em p h asize th e
im p o rtan ce o f sp ecific im m u n o g lo b u lin s (2 9 ) in m u co sal
an d in p atien ts w ith lesser sev erity o f th e d isease (4 0 )
H u m o ral ab n o rm alities are th erefo re im p o rtan t,
p articu larly to d ifferen tial d iag n o sis.
In tro d u ~ a o : D e s d e a d e c a d a d e 6 0 , te m -s e o b s e rv a d o a lte ra c ;:o e s d a im u n id a d e h u m o ra l n a h a n s e n ia s e . a s a u to -a n tic o rp o s a p re s e n ta m -s e e m fre q u e n c ia s d iv e rs a s , n e s te s p a c ie n te s , rn a is h a b itu a l m e n te n a h a n s e n ia s e v irc h o v ia n a , e m d o e n c ;:a d e lo n g a e v o lu c ;:a o e e m s u rto s re a c :;io n a is . V a ria c ;:a o n a s fre q u e n c ia s p o d e s e a trib u id a a d ife re n te s m e to d o lo g ia s e m p re g a d a s n a d e te c c ;:a o d o s a n tic o rp o s e a o g ru p o d e d o e n te s s e le c io n a d o . M a te ria l e M (H o d o s : E s ta re v i$ a o e n fo c ,a o s re s u lta d o s o b tid o s e m d iv e rs o s e s tu d o s d e a u to -a n tic o rp o s , c o m p le x o s im u n e s , c rio g lu b u lin a s , c o m p le m e n to s e ric o n a h a n s e n ia s e . D e s ta c a -s e ta m b e m , o s a n tic o rp o s c o n tra g lic o lip id e o s d o Mycobacterium leprae, .
c o m o o s a n tig lic o lip id e o s fe n 6 lic o s 'l, c u ja m a g n itu d e e v a ria v e l e d e p ~ n d e d o p a trim 6 n io g e n e tic o a p re s e n ta d o p e lo e n fe rm o .
RBSUMO
REFERENCES
I. A B E , M .; C H IM O N E , S .; H IR A K O , T . - R heum atoid
factor-like substance and antistreptolysin 0 antibody in leprosy
serum . Int. J.L epr. 35: 336-344, 1967.
2. A L B E R T , D .A .; W E IS M A N , M .H .; K A P L A N , R - T he
rheum atic m anifestations of leprosy
(H ansen disease). M edicine 59: 442-448,
1 980.
3. A L C O C E R , J.Y .; H E R R E R A , c.L .; G U D IN O , 1.; F R A G A ,
A . - (A bstract) Inflam m atory arthropathy in leprosy. A rth
R heum . 22: 587, 1979.
4. A N D E R S O N , D .C .; V A N S C H O O T E N , L .U .C .A .; B A R R Y ,
M .E .; JA N S O N , A .A .M .; B U C H A N A N , T .M .; D E V R IE S ,
R R P . - A M ycobacterium leprae specific hum an T cell
epitope cross-reactive w ith an H L A -D R 2 peptide. S cience
1: 242-259, 1988.
5. A T K IN , S .L .; E L -G H O B A R E Y , A .; K A M E L , M .; O W E N ,
J.P .; D IC K , W .c. - C linical and laboratory studies in patients
w ith leprosy and enthesitis. A nn. rheum . D is. 49:715-717, 1990.
6. A Z E V E D O , M .P .; M E L O , P .H . - A com parative study of
com plem entary activity of serum in polar form s of leprosy
and in the leprosy reactions. Int. J. L eprol 34:34-38, 1966.
7. B E R G O T , J.; N IC O L I, J.; Z IE G L E R , P .; D E N O R C H I, 1. _
E letrophoretic and im m unoeletrophoretic study of serum
proteins in leprosy. B ull. S oc. P athol. E xot. F iliales. 55:766-782, 1963.
8. B E R M A N , L .O . - E xudative arthritis in leprosy. (L etter)
A rth. R heum . 20:593, 1979.
9. B JO R V A T H , B .; B A R N E T S O N , E S .; K R O N V A L L , G .K
-Im m une com plexes and com plem ent hypercatabolism in
patients w ith leprosy. C lin. E xp. Im m unol. 26:388-396,
1976.
10. B O N F A , E . - A utoanticorpos na doen~ a de C hagas. S ao
P aulo. T ese (D outorado) - F aculdade de M edicina da
U niversidade de S ao P aulo. 1991, p.24
II. B O N F A , E .; L L O V E T , R ; S C H E IN B E R G , M .; S O U Z A ,
J.M .; E L K O N , K B . - C om parison betw een autoantibodies
in m alaria and leprosy w ith lupus. C lin. expo Im m unol.
70:529-537, 1987.
12. B O N O M O , L .; D A M M A C O , E ; T U R S I, A .; B A R B IE R I,
G . - L upoid features in a case of leprosy. Int. J.L eprosy
35:65-71, 1967.
13. B O N O M O , L .; D A M M A C O , F . - Im m une com plex
cryoglobulinaem ia in leprom atous leprosy: a pathogenetic
approach to som e clinical features of leprosy. C lin. expo
Im m unoI. 9: 175-181,1971.
14. B O N O M O , L .; T U R S I, A .; T R IM G L IA Z Z I, G.;D A M A C O ,
E - L E cells and antinuclear factors in leprosy. B rit. m ed.J.
2:689-690, 1987.
15. B O T H A M L E Y , G .; S W A N S O N B E C K , J.; A G U S N I,
I.;IL IA S , M .I.; K A R D JIT O , T .; G R A N G E , J.M .; IV A N Y I,
J. - A ntibodies to m ycobacterium tuberculosis in leprosy.
[L etter]. L ancet 1: 1098, 1987.
16. B R E IT S 1.; IV A N Y I, 1. - G enetic influences on the im m une
repertoire follow ing tuberculous infection in m ice.
Im m unology 71: 113. 1990.
17. B U L L O C K , W .E . - S tudies of im m une m echanism s in
leprosy. N ew E ngl. J. M ed 278:298, 1968.
18. B U L L O C K , W .E .; H O , M .E ; C H E N , M .S . - S tudies of
im m une m echanism s in leprosy: quantitative relationships
of IgG , IgA and IgM im m unoglobulins. J.L ab. C lin. M ed.
75:863-870, 1970.
19. B U R G E S S , P .J.; F IN E , P .E .M .; P O N N IG H A U S , J.M .;
D R A P P E R , C . - S erological tests in leprosy. T he sensitivity,
specificity and predictive value of E L IS A tests based on
phenolic glycolipid antigens, and the im plications for their
use in epidem iological studies. E pidem . Inf. 101: 159-171 ,
1988.
20. C A T H C A R T , E .S .; W IL L IA M S JR , R .C - A clinical and
serological study of latex fixation test in leprosy. - (A bstract)
A nn. Intern. M ed. 54(5): 1053-1 054, 1961.
21. C A T H C A R T , E .S .; W IL L IA M S JR , R C .; R O S S , H . - T he
relationship of the latex fixation test to the clinical and
serological m anifestations of leprosy. A m er. J.M ed.
31:758-765, 1961.
22. C E N IT E A U , M .; A D A M , c.; V E R R O U S T , P .; P A S T IC IE R ,
A .; S A IM O T ,
G.;
C O U L A N D , J.P .; L A N G U IL L O N , J. - L escom plexes im m unus et Ie com plem ent dans la lepre. N ouv,
P resse M ed. 10:3697-3700, 1981.
23. C H A V E Z -L E G A S P I, M .; G O M E Z -V A S Q U E S , A .;
G A R C IA D E L A T O R R E , I. - S tudy of rheum atic
m anifestations and serological abnorm alities in patients w ith
leprom atous leprosy.J. R heum atol. 12:738-741, 1985.
24. C H O I, E .K ; G A T E N B Y , P .A .; M C G IL L , N .W .; B A T E M A N ,
J.E ; C O L E , W .G .; Y O R K , J.R - A utoantibodies to type II
collagen; occurrence in rheum atoid arthritis, other arthritides,
autoim m une connective tissue disease,
and chronic inflam m atory syndrom es. A nn.
rheum . D is. 47:313-322, 1988.
25. C H R IS T IA N , C .L .; D E S IM O N E , A .R ; A B R U Z Z O , J.L _
A nti D N A antibodies in hyperim m unized rabbits. A rth.
R heum . 6:766, 1963.
26. C O H E N , A .S . - (ed.) L aboratory diagnostic procedures in
the rheum atic diseases 3rded., N ew Y ork, G rune & S tratton
Inc. 1985, p.145.
27. C O S S E R M E L L I-M E S S IN A , W .; L E V Y , M .; Y O S H IN A R I,
N .H .; C O S S E R M E L L I, W . - M iosite hanseniana sim ulado
derm atopolim iosite. A nais do X V III C ongresso B rasileiro
de R eum atologia, B ahia, 1990.
28. C O S S E R M E L L I-M E S S IN A , W .; B U E N O , c.; G A B U R O
JR ; N .; B A R R O S , P J.L .; F E S T A N E T O , c.; Y O S H IN A R I,
N .H .; C O S S E R M E L L I, W . - D etection of anticardiolipin
antibodies in leprosy patients. A nais do C ongresso del C ono
S ur. B uenos A ires, 16 - 19 de outubro, 1991.
29. C R E E , L A .; R A N C E , S .S .; B E C K , J.S . - M ucosal im m unity
in leprosy. Int. J.L eprosy, 57:318, 1989.
30. C R U A U D , P .; Y A M A S ID T A , J.T .; C A S A B O N A ., N .M .;
P A P A , E ; D A V ID , H .L . - E valuation of anovel
trehalose-2' -sulphate (SL-IV) antigen for case finding and
diagnosis of leprosy and tuberculosis. Res. Microbiol.
141:679-694, 1990.
31. DAVENPORT, M.P.; McKENZIE, K.R.; BASTEN, A.;
BRITTON, W.J. - The variable C-terminal region of the mycobacterium leprae 70-kilodalton heast shock protein is
the target for humoral immune responses. Infection and
Immunity. 60(3): 1170-1177, 1992.
32. DRUTZ, D.J.; GUTMAN, RA. - Renal manifestation of
leprosy glomerulonephritis a complication of erythema
nodosum leprosum. Am.
J.
Trop. Med. Hyg. 22:496-502,1973.
33. Editorial - Arthritis in leprosy. Arch. intern. Med. 144:421, 1984.
34. Editorial - Lepromatous rheumatoid. Lancet 2:748-749,
1982.
35. EDMUNDSON, W.F.; WOLCOTT, RR; OLANSKY, S.;
ROSS, H. Int.
J.
Leprosy, 22:440, 1954.36. ESCOBAR-GUTIERREZ, A.; AMESCUA-CHAVARRIA,
M.E.; PASTEN, S.; CASTRO, E.; FLORS, 0.;
RODRIGUES, O. Anticardiolipin antibodies in Mexican
lepromatous leprosy patients. (Letter). Int. Lepr. other
Mycobact. Dis. 58:723-724, 1990.
37. ESTRADA-PARRA, S.; ROJAS-ESPINOSA, 0.;
REYES-GOMEZ, P. - Isolation of polisaccharids from M.leprae and
M.lepraemurium and their reaction with sera from patients
with leprosy. In: Transactions of the 9th International Leprosy
Congress, London. Int.
J
.Leprosy 3:4, Pt2 abstract,Miscellaneous 231.
38. FRITZLER, M.J.; TAN. E.M. - Antinuclear Antibodies and the connective tissue diseases. In Cohen, AS. Laboratory
Diagnostic Procedures in the Rheumatic Diseases, 3rt
!ed.,
New York, Grune & Stratton Inc., 1985, p.207-247.
39. FURUKAWA, F.; KASHIHARA, M.; IMAMURA, S.;
OHSHIO, G.; HAMASHIMA, Y. Evaluation of
anti-cardiolopin antibody and its cross-reactivity in sera of patients
with lepromatous leprosy. Arch. Dermatol. Res
278:317-319,1986.
40. GORMUS, RJ.; OSASHI, D.K.; OHKAWA, S.; WALSH,
G.P.; MEYERS, W.M. - Serologic responses to
Mycobacterium leprae specific phenolic glycolipid I antigen
in sooth-mangabey monkeys with experimental leprosy. Int.
J.
Leprosy 56:537-545, 1988.41. GUPTA, RK; MUKHERJIA, R.D.; GUPTA, S.; SAMUEL, K.e. - Electrophoretic pattern of serum proteins in leprosy.
Int.
J.
Lepr. 144:453-455, 1976.42. HARBOE,M. - Rheumatoid factors in leprosy and parasitic
diseases. Scand.
J.
Rheumatol. (suppl) 75P:309-313, 1988.43. HARTMANN, M.G. - Arthritis in infectious diseases. Verh
Dtsch. Ges. Rheumatol. 3:59-66,1974.
44. HUNTER, S.W.; BRENNAN, P.J. Anovel phenolic
glycolipid from Mycobacterium leprae possible involved
in immunogenicity and pathogenicity.
J.
Bacteriol.147:728-735, 1981.
45. IVESON, J.M.I.; MCDOUGALL, A.e.; LEATHEM, A.J.;
HARRIS, H.J. - Lepromatous leprosy presenting with
polyarthritis, mYOSitis, and immune-complex
glomerulonephritis. Brit. med.
J.
3:619-621, 1975.46. JHA, P.;BALAKRISHNAN, K; TALWAR, G.P.; BHUTANI, L.K - Status of humoral immune responses in leprosy. Int.
J.
Leprol. 39: 14-19, 1971.47. KARAT, A.B.A.; KARAT, S.; JOB, e.K; FURNESS, M.A Acute exudative arthritis in leprosy, rheumatoid arthritis
-like syndrome in association with erythema nodosum
leprosum. Brit. med.
J.
3:770-772, 1967.48. KUMAR, B.; GANGULY, N.K; KAUR, S. - Complement profile in leprosy. Lepr. India 52:217-222, 1980.
49. LOUIE, J.S.; GLOVSKY, M. Complement determinations in the synovial fluid and serum of a patient with erythema
nodosum leprosum. Int.
J.
Lepr. Mycobact. Dis.43:242-245, 1975.
50. MACKWORTH-YOUNG, e.G.; HARRIS, E.N.; STEERE,
Ae.; et al.. - Anticardiolipin antibodies in Lyme Disease.
Arthr. Rheum. 31:1052-1056, 1988.
51. MASALA, C.; AMENDALEA, M.A.; NICTI, M.;
Riccarducci, R.; TARABINI, e.G.L.; TARABINI, e.G.
-Autoantibodies in leprosy. Int.
J.
Lepr. 47:171-175,1978.52. MATTHEWS, L.J.; TRAUTMAN, J.R - Clinical and
serological profiles in leprosy. Lancet 2:915-918, 1965. 53. MEGHLAONI, A.; HERBAGE, D.; HUC, A.; MONIER,
J.e. - Detection of anti-collagen type I and II antibodies by an immunoenzymatic technique (Elisa): results in rheumatoid
arthritis, systemic lupus erthematosus and leprosy. Ann.
immunol. 132:287-305, 1981.
54. MILLER, R.A.; WENER, M.H.; HARNISCH, J.P.;
GILLILAND, B.e. The limited spectrum of antinuclear
antibodies in leprosy.
J.
Rheum. 14:108-110,1987.55. MISSI, S.M.; ALMEIDA NETO, E.; SCHAF, S.;
GON<;ALVES, e.R; RODRIGUES, C.J.; MARGARIDO,
L.e. - Artrite especffica em pacientes com lepra. Rev. Hosp. Clin. Fac. Med. Univ. S.Paulo 40:22-26, 1985.
56. MORAN, C.J.; RYDER, G.; TURK, J.L.; WATERS, M.F.R. - Evidence for circulating immune complexes in lepromatus leprosy. Lancet. 2:572-573, 1972.
57. NAVALKAR, R.G. - Immunologic analysis of M. leprae antigens and human sera by means of gel diffusion methods. In: Transactions of the 9th International leprosy Congress,
London. Int.
J.
Leprosy 36:4 Pt2 abstract VII 97.58. NEVES, R.A.; TEIXEIRA, L.A.N.; NEVES, R.G.;
MANHAES, L.F. Avalia~ao da imunidade celular na
hansenfase indeterminada. Rev. bras. Malar. D. Trop. 34: 108-115, 1982.
59. NSIBAMBI, J.K. - Rheumatic manifestations in leprosy: a
case report. E. Afr. mcd. J60:805-808, 1983.
60. PELTIER, A.; CHRISTIAN, C.L. - The presence of the "Rheumatoid Factor" in sera form patients with syphilis. Arth. Rheum. II (1): 1-7, 1959.
61. PERNAMBUCO, J.e.A - Artrite na rea~ao hansenica.Hans. Int. 3:18-29,1978.
62. PERNAMBUCO, J.C.A. - Hansenfase: urn modelo de
colagenose. In: VERTZMAN, L; DE PAOLA, D.
Colagenoses. Rio de Janeiro, Epume, 1981.
6 3 . P E R N A M B U C O , J.C .A .; O P R O M O L L A . D .Y .A .;
T O L E N T IN O , M .M .; F L E U R Y , R .N . - A rth ritis in
le p ro m a to u s H a n se n 's d ise a se . In t. J. L e p ro sy . 4 7 (su p p I.2 ):3 5 3 -3 5 4 , 1 9 7 9 .
6 4 . P E T C H C L A I, B .; C H U T H A N O N D H , R ; R U N G R O U N G ,
S .; R A M S O O T A , T . -A u to a n tib o d ie s in le p ro sy a m o n g T h a i
p a tie n ts. L a n c e t 1 : 1 4 8 1 -1 4 8 2 , 1 9 7 3 .
6 5 . P E T R I, Y .; M E N D E S , E .Y .; B E IG U E L M A N , B . H isto lo g y
o f th e M itsu d a R e a c tio n o f h e a ltly a d u lts w ith n o k n o w n
c o n ta c ts w ith le p ro sy p a tie n ts. In t. J. L e p ro sy 5 3 :5 4 -5 4 5 , 1 9 9 5 .
6 6 . P IN T O , L .; B A R B IE R I, G . - L a sie ro p o sitiv a re u m a to id n e lla
le b b ra . G . M a la d . In fe U . 1 6 :4 5 6 -4 6 2 , 1 9 6 4 .
6 7 . P L O T Z , e .M .A .; S IN G E R , J.M . - T h e la te x fix a tio n te st. II
re su lts in rh e u m a to id a rth ritis. A m . J. M e d . 2 1 :8 9 3 , 1 9 5 6 . 6 8 . R A B E L L O , E E . - D isso c ia te d re sp o n se to rh e u m a to id fa c to r
in le p ro m a to u s h a n se n ia sis. [L e tte r]. J. A m e r. m e d . A ss.
2 2 6 : 1 2 2 8 , 1 9 7 3 .
6 9 . R A M O S , O .S .; B O T A S S O , O .A .; M O R IN I, J.e .; S E G A L
-E IR A S , A . - E v a lu a tio n o f c irc u la tin g im m u n e c o m p le x e s in
le p ro sy . R e v . A rg e n t. M ic ro b io l. 2 0 : 1 6 3 -1 7 0 , 1 9 8 8 . 7 0 . R A O , T .D .; R A O , P .R . - S e ru m im m u n e c o m p le x e s in
e rth e m a n o d o su m le p ro su m re a c tio n s o f le p ro sy . In d ia n J. L e p ro sy 6 8 : 1 8 9 -1 9 5 , 1 9 8 8 .
7 1 . R O IT T , I. - E sse n tia l im m u n o lo g y , S ix th E d . L o n d o n ,
B la c k w e ll S c ie n tific P u b lic a tio n s O x fo rd , C h a p te r 6 ., p . 8 5
-1 0 0 , 1 9 8 8 .
7 2 . R O JA S -E S P IN O S A , 0.; M E N D E Z -N A V A R R E T E , I.; E S T R A D A -P A R R A . S . - P re se n c e o fC lg re a c tiv e im m u n e
c o m p le x e s in p a tie n ts w ith le p ro sy . C lin . e x p o Im m u n o l.
1 2 :2 1 5 -2 2 2 , 1 9 7 2 .
7 3 . R O S S , H .; B U T L E R , e .E ; L A N K A IT IS . R .B .e . - R e a c tiv e
p ro te in s in th e se ra o f p a tie n ts w ith le p ro sy . In t. J. L e p r.
2 7 :1 2 9 -1 3 3 , 1 9 5 9 .
7 4 . R O Y , A .; A G A R W A L , A .; R A L H A N , R . A n
ti-a rti-a b in o g ti-a lti-a c tti-a n Ig M lIg G ra tio : a sc re e n in g in d e x fo r le p ro sy
p a tie n ts. In d ia n J. L e p r. 6 2 :4 3 5 -4 4 2 , 1 9 9 0 .
7 5 . S A A D , M .H .; M E D E IR O S , M .A .; G A L L O , M .E ; G O N T IJO ,
P .P .; F O N S E C A , L .S . - Ig M im m u n o g lo b u lin s re a c tiv y w ith
th e p h e n o lic g ly c o lip id -1 a n tig e n fro m M y c o b a c te riu m
le p ra c e in se ra o f le p ro sy p a tie n ts a n d th e ir c o n ta c ts. M e m . In st. O sw . C ru z 8 5 : 1 9 1 -1 9 4 . 1 9 9 0 .
7 6 . S A G H E R , F .; S H E S K IN , 1 .; Z L O T N IC K .A : e t a \..
-C o m p le m e n t a n d im m u n o lo g ic d e te rm in a n ts in le p ro sy a n d
re a c tio n . In t. J. L e p ro l. 3 9 :5 4 1 -5 5 3 , 1 9 7 1 .
7 7 . S A H A , K .; C H A K R A B A R T Y , A .K . - S e ru m c o m p le m e n t
p ro lile s in h u m a n le p ro sy a n d its c o m p a riso n w ith im m u n e
c o m p le x d ia se s. In t. J. L e p ro l. 4 5 : 3 2 7 -3 3 7 , 1 9 7 7 . 7 8 . S A lT Z , E .W .; D IE R K S , R .E .; S H E P A R D , e .e . In t. J.
L e p ro so l. 3 6 :4 0 0 , 1 9 6 8 .
7 9 . S A N T IA G O , M .B .; C O S S E R M E L L I, W .; T U M A , M .E ;
P IN T O M .N .; O L IV E IR A . R M . - A n tic a rd io lip in a n tib o d ie s
in p a tie n ts w ith in fe c tio u s d ia se a se . C lin . R h e u m . 8 :2 3 -2 8 , 1 9 8 9 .
8 0 . S E H G A L , Y .N . - E le tro p h o re tic p a tte rn s o f se ru m p ro te in s
in le p ro sy In t. J. le p r. 3 6 : 4 1 3 -4 1 6 , 1 9 6 8 .
8 !. S E H G A L , Y .N - S H A R M A , Y .K . - C o m p re h e n siv e
e v a lu a tio n o f c o m p le m e n t c o m p o n e n ts in th e c o u rse o f th e
ty p e I (le p ra ) a n d ty p e II (E N L ) re a c tio n s In t. J. D e rm a to l.
2 8 :3 2 -3 5 , 1 9 8 9 .
8 2 . S H A R M A ., Y .K .; S A H A , K .; S E H G A L , Y .N . - S e ru m
im m u n o lo g lo b u lin s a n d a u to a n tib o d ie s d u rin g a n d a fte r
e ry th e m a n o d o su m le p ro su m . In t. J.le p ro sy 5 0 (2 ): 1 5 9 -1 6 3 , 1 9 8 2 .
8 3 . S IN G E R , J.M .; P E R A L T A , E M .; L Y O N S , H .D .; P L O T Z ,
e .M . - P re se n c e o f " S e ro lo g ic a lly a c tiv e m a c ro g lo b u s" in
se ra o f so m e p a tie n ts w ith a c tiv e p u lm o n a ry tu b e rc u lo sis.
A rth . R h e u m . 4 : 1 2 4 , 1 9 6 1 .
8 4 . S U L C E B E . G .; N A K U C I, M . - A ti-p h e n o lic g ly c o lip id 1
Ig M a n tib o d ie s in le p ro sy p a tie n ts a n d in th e ir h o u se h o ld
c o n ta c ts. L e p ro sy R e v . 6 1 :3 4 1 -3 4 6 , 1 9 9 0 .
8 5 . V A L E N T IJA , R M .; F A B E R , W .R ; L A I, A .; F A T , R E
-Im m u n e c o m p le x e s in le p ro sy p a tie n ts fro m a n e n d e m ic a n d
n o n e n d e m ic a re a s. C lin . Im m u n o l. Im m u n o p a th . 2 2 : 1 9 4 -2 0 -2 , 1 9 8 2 .
8 6 . W E M A M B U , S .N .C .; T U R K , J.L .; W A T E R S , M .F .R .;
R E E S , R .J.W . - E ry th e m a n o d o su m le p ro su m : a c lin ic a l
m a n ife sta tio n o f th e A rth u s p h e n o m e n o n . L a n c e t 2 :9 3 3 -9 3 5 , 1 9 6 9 .
