40
Immunopathogene›i› of Idiopathic Thrombocytopenic Purpura ITP
2002
UniverIity Children´I HoIpital BaIel¸ Switzerland
e-mail: paulimbach unibaI.ch
IT manife›t› a› immune mediated, de›tructive
thrombocytopenia. The etiology of IT i› ›till unknoun.
Immunologically an antigenic challenge or an au-
toimmune ›timulu› induce› interaction betueen an-
tigen pre›enting cell› and T-lymphocyte›. Through
›ignal mechani›m› T-cell activation and B-cell anti-
body production occur. Regulatory mechani›m of T-
cell› and antiidiotypic antibodie› direct the degree and
duration of the phy›iologic immune re›pon›e. In IT the
immune re›pon›e and the ›elftolerance mechani›m are
altered in the pre›ence of an antigen ›timulu›.
Wainly 3 element› are involved in the pathophy›i-
ology of IT : the platelet, the cellular and humoral
immune re›pon›e, the mono-macrocytic phagocyto›i›
mediated by +c-receptor›.
THE TLATELETS
The platelet function i› balancing betueen inflam-
matory, procoagulant, antithrombic and fibrinolytic
propertie›. When platelet reactive antibodie› are
overuhelming actively the platelet function get› out of
balance: bleeding or thrombo›i› are ›ymptom› of the
advanced ›tate of di›order. latelet› vary in form,
›ize, den›ity, age a› uell a› reactivity according to
polimorphi›m of major glycoprotein› (G ’›). latelet›
trigger the immune re›pon›e from the fir›t ›timulu› to
irrever›ible participation in cell to cell reation›. In IT
mainly the numeric balance› are di›turbed.
THE IWWUNE SYSTEW
In IT the immunopathogene›i› of platelet› i› an-
tibody mediated under the control of T-helper cell›
ITP
HCWATOLOGIA ◆ Polvmen 7 - º 2¸
Dr. T. Imbach
CONPCRCNCIA
HCWATOLOGIA, Vol. 7 Nº 2: 40-
41
Wayo-Octubre, 2003
and related cytokine›. latelet›‘ (auto)antigen driven T-
cell clone› and Interleukin›, mainly Interleukin-2 (IL-2)
direct autoreative B-cell› to ›ecret (auto) anti- bodie›.
In acute IT ›pecific antibody (e.g. again›t
Varicella zo›ter viru›) may cro››react uith platelet
antigen: molecular mimicry occur›. ThO or Th2 ex-
pre››ion uith TG+-ß a› potent immuno›uppre››ive
modulator among the cytokine pattern ›eem› to cor-
relate uith tran›ient IT .
In chronic IT autoimmune target› on platelet› are
mo›tly G IIb/IIIa uith different location› of epitope›, G
Ib/IX and rarely G Ia/IIa, IV and V. Th1 pattern and
abnormal activation of autoreative B- cell› characterize
autoimmunity in chronic IT . With aberrant immune
re›pon›e circulating and platelet- a››ociated
autoantibodie› can be detected by capture a››ay›
(immunoblot-, WAI A-a››ay). The ›en›itivity (po›itive
re›ult› in patient› uith IT ) i› 49 - 66%, the
›pecificity (negative re›ult› in patient› uith nonimmune
thrombocytopenia) i› 7å - 95%.
(Auto-)antibodie› have a hypervariable region uith
amino-acid ›epuence› uhich are ›pecific for each
individual antibody and uhich never before uere
encountered by the ho›t and, therefore, are foreign to the
ho›t uho ›tart› to produce neutralizing, regula- tory
antibody. The patient›‘ oun antidiotypic antibod- ie› or
tho›e in IVIG preparation› regulate/ dounmodulate the
production of (platelet) antibodie›.
THAGOCYTOSIS AND PCy-KECETTOKS (PCyK)
Among the cla››e› of +cR› the lou affinity +cIIA
uith the capacity of IgG1 and 3 binding and +cIIIA
uith IgG2 binding are prominent mediator› of platelet
clearance in IT and bind mainly immunocomplexed
antibodie›. High affinity +cRI uhich bind› monomeric
IgG ›eem› to play a minor role in IT . Several
polimorphi›m› exi›t for +cII and III in human› uhich
alter affinite› for antibodie›. The inhibitory +cRIIb
lead› to co-cro››linking uith B-cell receptor› re›ulting in
cell inactivation (no phagocyto›i›).
The immunologic characteri›tic› of +cR› are al›o
important in the context of the immunomodulatory
effect of IVIG treatment: IVIG dimer and multimer
›eem› to block +c-receptor› more actively than
monomeric IVIG. On the other hand the dimer›/
multimer› are re›pon›ible for marked ›ide effect› of
IVIG treatment. IVIG increa›e the pre›ence of
inhibitory +cRIIB and prevent IT in a mice model. The
immunopathology of IT i› a model for altered
immune re›pon›e. Similar immunopathologic
41
event› are pre›ent in other (auto)immune related
di›order›. The mechani›m of action of T-cell regulatory
drug›, of IVIG and other biologic therapeutic› can be
documented by mea›uring change› of the different
component› of the immune re›pon›e.
In the future, monoclonal antibodie› again›t the
different ›tep› of the immune re›pon›e (e.g. anti-T cell
antibodie›, CD20 antibody (rituximab), anti-+c- receptor
antibodie›) may provide ›pecific therapie› in IT and
other immune related di›order›.
KEPEKENCES
see Supplemelt oL State-of-the-Art Cxpert Weetilg oL ITP. ƒ
Ped Hematol OLcol 2003 (il press), especially the articles
by R. Rekomäki, A. Crou ald A. Lazarus, ƒ. Semple, R.
WcWillal ald
D. Ciles