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Zaburzenia odporności
Niedobory odporności typu komórkowego
i skojarzone
Barbara Zamorska
Genetic loci of primary immunodeficiency due to defects of
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lymphocytes
Disease gene/protein gene lokation
Wiskott-Aldrich syndrome WASP Xp11.23-p11.22
X-linked SCID Il2RG/ (Å‚c) receptor Xq13.1-q21.1
X-linked lymphoprolferative syndrome SH2D1A/SAP Xq25
MHC class II deficiency RFX5 1q21.1-q21.3
CD45 deficiency CD45G/CD45 1q31-q32
ZAP-70 deficiency ZAP70 2q12
Mendelian suscept. to mycobact.inf. STAT1 2q32.2-q32.3
SCID Il7RA/Ä… chain of Il7 recep. 5p13
Mendelian suscept. to mycobact.inf. Il12B 5q31.1-q33.1
MHC class I deficiency TAP1,TAP2 6q21.3
Mendelian suscept. to mycobact.inf. IFNGR1 6q23-q24
Nijmengen breakage syndrome NBS1/nibryn 8q21
CD25 deficiency Il2RA/Ä… chain Il2 recep. 10p15-p14
Athabascan SCID Artemis 10p13
Di George syndrome DGCR2/deletion 10p13 10p13
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Genetic loci of primary immunodeficiency due to defects of
lymhocytes
Disease gene/protein gene lokation
ALPS TNFRSF6/FAS (CD95) 10q24.1
SCID RAG1,RAG2 11p13
Ataxia-teleangiectasia ATM 11q22.3
CD3 deficiency CD3G,CD3E/Å‚µ CD3 comp. 11Q23
MHC class II deficiency RFXAP 13q14
SCID-PNP deficiency PNP 14q13.1
MHC class II deficiency MHC2TA 16p13
MHC class II deficiency RFXANK 19p12
Mendelian suscept. to mycobac. inf. IL12RB1 19p13.1
SCID JAK3 19p13.1
SCID-ADA deficiency ADA 20q13.11
Mendelian suscept. to mycobac. inf. IFNGR2 21q22.1-g22.2
DiGeorge syndrome/velocardiofacial synd. DGS1/deletion 22q11 22q.112
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Classification of SCID by lymphocyte phenothype
Classification of SCID by lymphocyte phenothype
T(-)B(+)NK(-)
T(-)B(+)NK(-)
(1) Mutation in common Å‚ chain (Å‚c), Il 2RG gene, X-linked
(1) Mutation in common Å‚ chain (Å‚c), Il 2RG gene, X-linked
(2) Mutation in Jak3 enzyme, JAK3 gene, AR
(2) Mutation in Jak3 enzyme, JAK3 gene, AR
T(-)B(+)NK(+)
T(-)B(+)NK(+)
(3) Mutation in Ä… chain of Il-7 receptor, Il7RA gene, AR
(3) Mutation in Ä… chain of Il-7 receptor, Il7RA gene, AR
T(-)B(-)NK(-)
T(-)B(-)NK(-)
(4) ADA deficiency,ADA gene, AR
(4) ADA deficiency,ADA gene, AR
(5) PNP deficiency, PNP gene, AR
(5) PNP deficiency, PNP gene, AR
T(-)B(-)NK(+)
T(-)B(-)NK(+)
(6) RAG1 or RAG2 deficiency, RAG1 or RAG2 gene, AR
(6) RAG1 or RAG2 deficiency, RAG1 or RAG2 gene, AR
(7) Omenn's synd., mutation in RAG1 or RAG2 leading to partial loss of function, AR
(7) Omenn's synd., mutation in RAG1 or RAG2 leading to partial loss of function, AR
(8) Athabascan or Navajo SCID, mutation in Artemis gene product, AR
(8) Athabascan or Navajo SCID, mutation in Artemis gene product, AR
T(-)B(+)
T(-)B(+)
(9) CD45 deficiency, CD45 gene, AR
(9) CD45 deficiency, CD45 gene, AR
(10) CD3 deficiences, mutations in CD3Å‚ or CD3µ gene, AR
(10) CD3 deficiences, mutations in CD3Å‚ or CD3µ gene, AR
T(+)B(+)
T(+)B(+)
(11) ZAP-70 deficiency, ZAP70 gene, AR
(11) ZAP-70 deficiency, ZAP70 gene, AR
(12) Il-2 deficiency, unknown defect
(12) Il-2 deficiency, unknown defect
(13) CD25 deficiency, defect in Ä… chain IL-2 receptor, Il2RA gene, AR
(13) CD25 deficiency, defect in Ä… chain IL-2 receptor, Il2RA gene, AR
(14) MHC type I deficiency, mutation in either TAP1 or TAP2 gene, AR
(14) MHC type I deficiency, mutation in either TAP1 or TAP2 gene, AR
(15) MHC type II deficiency, mutation in one several genes critical to HLA class II
(15) MHC type II deficiency, mutation in one several genes critical to HLA class II
transcription such as MHC2TA,RFX5,RFXANK,RFXAP, AR
transcription such as MHC2TA,RFX5,RFXANK,RFXAP, AR
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X-linked SCID Il2RG/ (Å‚c) receptor Xq13.1-q21.1
składnik receptorów: Il 2, Il 4, Il 7, Il 9, Il 15, Il 21.
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SCID
Defekt genów rekombinacji
Defects in the recombinase
activating genes-RAG1
and RAG2.
SCID RAG1,RAG2 11p13
Omenn s syndrom (OS),
Artemis, ( DNA repair factor)
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chromosome 1 chromosome 13
RFX5 RFXAP
chromosome 16
CIITA
chromosome 19
CIITA
CIITA
+
RFXANK
RF
RF
X
X
chromosome 6
Zespół nagich limfocytów
MHC class II genes (Reith, 1999)
BLS to choroba genów regulacji
(disease of gene regulation).
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Zespół Di Georga
(Di George syndrome DGS, CATCH 22)
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Zespół Wiskotta Aldricha
(Wiskott(1936)-Aldrich(1954) syndrome protein WAS),
X-linked disorder
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Defects in pathways of cell death
X-linked lymphoprolferative syndrome SH2D1A/SAP Xq25
XLP, (Purtilo or Duncan s disease)
B
B
T
T
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Defects of DNA repair
A-T, Ataxia-teleangiectasia, AR
NBS Nijmegen breakage syndrome, AR
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Diagnoza niedoboru
Diagnoza niedoboru
NawracajÄ…ce infekcje, ostry przebieg nawracajÄ…cych infekcji, oportunistyczne
infekcje, niewyjaśniona leukopenia lub limfopenia <1000 cm3,
trombocytopenia
Badanie
" Atrofia peryferyjnych węzłów limfatycznych i migdałków
" Brak cienia grasicy
" Zakażenia kości, wątroby, wrzody
" Hepatosplenomegalia
" Zaburzenia wzrostu
" Inne nieprawidłowości wrodzone
.
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Testy immunologiczne:
" Obecność różnych typów komórek we krwi
" Subpopulacje limfocytów
" Stężenie immunoglobulin
" Aktywność fagocytarna świeżo izolowanych leukocytów i monocytów
" Obecność i aktywność składowych dopełniacza
Testy funkcji limfocytów
Identyfikacja genu