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Guillain-Barre Syndrome
What Is Guillain-Barre Syndrome (GBS)?
Guillain-Barre Syndrome (GBS) is a rare, post-infectious, inflammatory autoimmune disease
that is characterized by an ascendin limb !ea"ness and numbness in the e#tremities that can
proress, in some cases, to paralysis ($u"i, %&&'). (he annual incidence in the population
ranes from &.)-).& cases per population of *&&,&&&. GBS can be di+ided into three subtypes
that can be differentiated throuh electrodianostic techni,ues- acute inflammatory
demyelinatin polyradiculoneuropathy (.I/0), acute motor a#onal neuropathy (.1.2),
acute motor and sensory a#onal neuropathy (.1S.2), and 1iller 3isher syndrome (13S)
(4u!abara, %&&)).
Figure 1. /epiction of GBS subtypes and their relationships accordin to type of neuropathy
!ithin the GBS classification. (Imae from 5o et al., *667. 8opyriht *667 by .nnual
9e+ie!s, Inc. 0ermission pendin.)
.I/0 is the most common form of GBS in de+eloped countries accountin for 6&: of cases
(1oran et al., %&&'). GBS can occur at all aes and its de+elopment is usually associated !ith
infections by bacteria and +iruses. (he mechanism proposed thus far for the de+elopment of
GBS is molecular mimicry. In summary, the body mounts an antibody response aainst a
pathoen protein that resembles neural lycolipids (anliosides), resultin in an an attac" on
the peripheral ner+ous system. 1ost patients reco+er e+entually !ith +aryin derees of
ner+e damae. 5o!e+er there is an 7-*&: mortality rate associated !ith GBS attributable to
respiratory failure in ad+anced cases (4u!abara, %&&)). (reatments consist of
immunolobulin therapy or plasma e#chane (alon !ith intra+enous corticosteroids in some
cases) (5arel and Shoenfeld, %&&'; Shahar, %&&<).
Infection and 0eripheral 2er+ous System
Inflammation 9esponse (=+er+ie!)
Infection
1ost of the pathoens that are "no!n to cause GBS ain entry to the body throuh mucosal
or ut epithelium. (hey can enter the body by the use of multifenestrated cells or other
mechanisms to cause an infection. (he innate immune response results in the upta"e of the
pathoens by immature antien presentin cells (.08s). .fter miration to lymph nodes, a
mature, differentiated .08 can present peptides in 158 class II molecules and acti+ate 8/)
( cells that reconize antiens from the infectious pathoen. B cells can be acti+ated as !ell
by ne!ly acti+ated (h% cells. (his produces a cell mediated and humoral response aainst the
pathoen (>ane!ay, %&&'). In the case of C. jejuni infection, antibodies !ill be produced,
leadin to acti+ation of the complement system and phaocytosis of the bacteria. 5o!e+er,
in rare cases the antibodies produced aainst certain C. jejuni antiens !ill also bind to
anliosides of the neur+ous tissue causin complement acti+ation and damae by
phaocytes. (his results in damae to peripheral ner+ous tissues, !hich leads to
demyelination and a#onal damae (4u!abara, %&&)).
0eriheral 2er+ous System Inflammatory 9esponse
(he peripheral ner+ous system refers to the net!or" of ner+ous tissue beyond the central
ner+ous system (brain and spinal cord). (he peripheral ner+es are co+ered by a blood-ner+e
barrier that pre+ents the normal infiltration of macromolecules. 5o!e+er, the e#ception to
this is that lymphcytes can mo+e in and out of peripheral ner+ous tissue. (his allo!s for
immune protection of the macrophaes and endothelial cells that reside in the tissue. In the
case of GBS, !hich is an inflammatory disorder, autoantibodies are able to cross the blood-
ner+e barrier !hile in its normal state. (he blood ner+e barrier is made up of endothelial cells
!ith tiht ?unctions that can be modified under inflammatory conditions to allo! passae of
effector cells and macromolecules. 5o!e+er, !hen the autoantibodies cross the barrier and
bind to anliosides of neural tissue, they can acti+ate complement cascades and the resident
macrophaes by their 3cIII receptors inducin cyto"ine production and inflammation !ithin
the ner+e tissue. It !as also found that endoneural macrophaes had the capacity to e#press
8/* (8/*a, b, and c), !hich allo!s them to present lycolipids such as anliosides to some
( cell subsets alon !ith dendritic cells (5uhes et al., %&&<). (he inflammation due to
cyto"ines and causes recruitment of leu"ocytes and damae to the ner+e tissue by one of four
mechanisms- 8/7 ( cell lysis, complement-mediated attac", cyto"ine and free radical
damae +ia phaocytes, and antibody-mediated interference of ner+e conduction (5o et al.,
*667). (here are se+eral places in the peripheral ner+ous system !here the inflammation
response of GBS can bein, dependin on the subtype that de+elops and infectious pathoen.
(hese locations are illustrated in 3iure % and include- dorsal root anlia, nodes of 9an+ier,
and sch!ann cell myelin (5o et al., *667).
Figure 2 . @ocations of GBS peripheral ner+e attac" in peripheral ner+ous system. a) /orsal
root anlia can be the taret of an antibody response in 13S. b) 2odes of 9a+ier are a taret
of immune response in .1.2. c) Sch!ann cell myelin surface proteins can be the taret of
antibody bindin in .I/0. d) 2euromuscular ?unction (not "no!n to be in+ol+ed !ith GBS).
(Imae from 5o et al., *667. 8opyriht *667 by .nnual 9e+ie!s, Inc. 0ermission pendin.)

0athoens and .utoimmunity in GBS
Subtypes
(!o-thirds of GBS cases are associated !ith prior acute infection of se+eral bacterial species
and +irusus. Campylobacter jejuni, cytomealo+irus, Apstein-Barr +irus, Mycoplasma
pneumoniae, Haemophilus influenzae, and Baricella-zoster +irus ha+e been found in patient
serum after the onset of GBS (4u!abara, %&&)). (he most commonly proposed mechanism
for the de+elopment of autoimmune disease is molecular mimicry ($u"i, %&&'). 1olecular
mimicry refers to the situation !here the pathoen and host share nearly identical antiens,
!hich induces an antibody and ( cell immune response that is cross reacti+e. (here is more
than one !ay that an immmune response can become cross-reacti+e. (he pathoen and host
can ha+e homoloous or identical amino acid se,uences or the host B cell receptors and (
cell receptors can reconize non-homoloous peptides (.n et al., %&&)). (he stronest
e+idence for the molecular mimicry hypothesis has come from disco+eries in research !ith
C. jejuni strains, the most common pathoen associated !ith GBS (specifically .1.2)
(2eisser et al., %&&&; $u"i, %&&'). Since definite mechanisms and e+idence of correlation
bet!een autoimmune responses and infection are limited in the cases of many pathoens
listed abo+e, only those !ith e+idence-based correlations !ith GBS subtypes !ill be further
described.
.I/0-associated Infection
Figure 3. Immunopatholoy of .I/0. .) Immunostainin sho!in 8Cd surroundin t!o
ner+e fibers indicated by asteris"s (D) B) 8omplement acti+ation and influ# of calcium alon
!ith demyelination. 8) 8omplement-mediated acti+ation of macrophaes. /) /epiction of
patholoy in .I/0 in+ol+in complement acti+ation and macrophae-mediated
demyelination. (Imae from 5o et al., *667. 8opyriht *667 by .nnual 9e+ie!s, Inc.
0ermission pendin. )
8ytomealo+irus (81B), a cause of respiratory tract infections, is the second most common
pathoen lin"ed to cases of GBS in Aurope and >apan. .utoantibodies aainst the human
anlioside G1% ha+e been isolated in patients !ith a 81B infection and GBS symptoms.
5o!e+er, no definiti+e epitope mimics ha+e been described despite the fact that 81B is
correlated !ith so many cases of .I/0. /e+elopment of .I/0 is seen predominantly in the
cranial and sensory ner+es as opposed to motor ner+es. .lso, the immune response elicited in
.I/0 is focused on the sch!ann cell or myelin sheath. /amae to the myelin or sch!ann cell
results in demyelination that is characteristic of .I/0 (3iure C) (4u!abara, %&&)).
.1.2-associated Infection
Infection by C. jejuni, a cause of bacterial astroenteritis, is the leadin cause of .1.2
!orld!ide (4u!abara, %&&); $u"i, %&&'). Studies sho! that the production of autoantibodies
by C. jejuni infection occurs in only * out of C%7' patients !ith C. jejuni enteritis (4oa et
al., %&&<). .lso, e+idence of host susceptibility has been sho!n for patients !ith 5@. BC'
and 5@. /EB *D&C, but because of conflictin data, the results are inconclusi+e (4u!abara,
%&&)). It has been found that only certain strains of C. jejuni are associated !ith GBSF.1.2
cases. (he strains are di+ided by serotype based on their lo! molecular !eiht type
lipopolysaccharide (@0S), called lipooliosaccharide (@=S). Serotypes most commonly
associated !ith .1.2 !ere 5S-*6 and 5S-)*. .lso, a polymorphism in the ene
cstII((hr'*) has been found to be closely associated !ith de+elopment of anti-G1* and anti-
G/*a autoantibodies (4oa et al., %&&<).
Figure 4 . Similarity bet!een human anlioside G1* and G1*-li"e epitope of 8. ?e?uni
@=S. (Imae from .n et al., %&&). 9eproduced !ith permission of the author.)
(he hypothesis of molecular mimicry is based on the fact that the bacterial @=S induces IG,
I., and I1 auto anitibodies aainst human anliosides due to @=S anlioside-
mimic"in epitopes (3iure )) (1oran et al., %&&'). .utoantibodies ha+e been isolated in
GBS patientsG serum and found to reconize C. jejuni @=S and human anliosides G1*,
G1*b, G/*a, and Gal2.c-G/*a epitopes, pro+idin e+idence for molecular mimicry (.n
et al., %&&); $u"i, %&&'). 3urthermore, 1oran et al. concluded that the IG @=S-induced
anti-G1* antibodies bound to sites at the nodes of 9an+ier in humans (3iure '). (his is
important because other studies ha+e concluded that antibodies bound to nodes of 9an+ier
disrupt 2aH and 4H channels, interferrin !ith ner+e conduction (%&&').
Figure 5 . Immunopatholoy of .1.2 subtype of GBS. .) immunostainin of 8Cd at the
node of 9an+ier. B) Bentral root node of 9an+ier lenthened alon !ith macrophaes. 8)
0eria#onal space !ith macrophae inside e#tendin processes around the a#on. /) /epiction
of .1.2 patholoy in+ol+in antibodies, complement, and macrophae in+asion. (Imae
from 5o et al., *667. 8opyriht *667 by .nnual 9e+ie!s, Inc. 0ermission pendin.)
Figure 6. 1echanism of molecular mimicry in+ol+ed in GBS autoimmune response after 8.
?e?uni infection. (Imae from .n et al., %&&). 9eproduced !ith permission of the author.)
13S-associated Infection
Infection by 8. ?e?uni if also implicated in the de+elopment of 13S by the same mechanism
of molecular mimicry. 13S patients present !ith symptoms similar to other forms of GBS
alon !ith problems controlin eye mo+ements, or ophthalmopleia. .utoantibodies ha+e
been isolated from these patients that bind to human anlioside GE*b as !ell as the GE*b
epitope present !ithin the @=S of 8. ?e?uni isolated from 13S patients. .lso, the dominant
8. ?e?uni serotypes associated !ith 13S !ere 5S-% and 5S-). (he ene polymorphism
associated !ith the de+elopment of anti-G/*b autoantibodies !as found to be cstII(.sn'*)
(4oa et al., %&&<). (his pro+ides a clear lin" to the clincal presentation of 13S since the
GE*b anlioside is found predominantly in human oculomotor ner+es (.n et al., %&&);
4u!abara, %&&)).

Affecti+e (reatments
(he first effecti+e treatment option for GBS !as plasmapheresis, or plasma e#chane (0A).
(his treatment in+ol+es remo+in plasma from the blood and usin centrifual blood
separators to remo+e immune comple#es and possible autoanitbodies. (he plasma is then
rein?ected into the patient alon !ith a ': albumin solution to compensate for lost protein
concentration. 1any studies ha+e found that this treatment in+ol+es hih ris"s and ad+erse
effects for hemodynamically unstable patients (Shahar, %&&<). .lso, studies found that the
most effecti+e number of treatments for moderate and se+ere cases of GBS !as four. . post
treatment !orsenin of symptoms !as seen as !ell in *&: of patients in some studies
(4u!abara, %&&)). 9is"s and conclusions li"e these bean the search for effecti+e and safer
treatments.
.nother treatment for GBS is IB administration of immunolobulins (IBI). (he anti-
idiotypic antibodies used ha+e been sho!n to modulate the humoral response in their ability
to inhibit autoanibodies and suppress autoantibody production. By inhibitin autoantibodies,
the complement-mediated damae can be attenuated. IBIGs also bloc" bindin of 3c(amma)
receptors pre+entin phaocytic damae by macrophaes. Studies ha+e sho!n that an
optimal amount of IBI is )&&mF" o+er si# days. In comparison studies, 0A and IBI !ere
pro+en to be similar in o+erall effecti+eness, and no increase in effecti+eness !as seen by
combinin therapies. 5o!e+er, it !as noted that IBI !as considered safer by its reduced
ris"s and complications (5arel and Shoenfeld, %&&'; Shahar, %&&<).

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K 8opyriht %&&< /epartment of Bioloy, /a+idson 8ollee, /a+idson, 28
%7&C<