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Juan José Cano Fernández
Valeria Guerra Espinosa
Recent researchs support the important role
of the cytokine genes in autoimmune
diseases, high serum levels of TNF-alfa and
IFN- gamma wich are a very important pro-
inflammatory citokines have been reported in
SLE a complex disease that causes a high
rate of mortality worldwide.
 Is a prototypic autoinmune complex disease
which is characterized by excessive
production of autoantibodies against a broad
range of self-antigens.
 For SLE diagnosis, the patient must satisfy at
least 4 criteria accordin to the SLE
classification
Polymorphism is the occurrence of two or
more clearly different morphs or forms, also
referred to as alternative phenotypes, in the
population of a species.
 Is the variation of a gene in a population
 Is a cell signaling
protein (cytokine)
involved in systemic
inflammation and is
one of the cytokines
that make up the acute
phase reaction.
 the regulation of immune cells
 endogenous pyrogeninduce fever
 apoptotic cell death
 inflammation
 inhibit tumorigenesis and
 viral replication
 respond to sepsis via IL1 & IL6
 Interferon gamma is a
cytokine that is the
only member of the
type II class of
interferons. The
existence of this
interferon, which early
in its history was
known as immune
interferon
 innate and adaptive immunity against viral,
bacterial and protozoal infections.
 activator of macrophages and
 inducer of Class II MHC
Polymorphisms
TNF- α IFN-Y
-308
G>A
+874
A>T
SLE
This article is based on finding how the
TNF-alfa and IFN-gamma are associated with
immune factors especially in the systemic
lupus erythematosus (SLE) and if this genes
polymorphism could affect the susceptibility
and severity of the diasease.
•72 Mujeres
•53 Hombres
•23.4 ± 4.4
años
125
PACIENTES
CON LES
(LN)
•66 Mujeres
•46 Hombres
•28.3± 6.2 años
112
PACIENTES
SALUDABLES
Centro de urología y
nefrología, universidad
Mansoura ,Egipto.
Diagnostico de los
pacientes: criterios de LES
de la Universidad
Americana de
Reumatología
237 PACIENTES
EN TOTAL
CLASIFICACION DE LUPUS
NEFRITICO
CLASE I
Glomérulo
normal
0 casos
CLASE II
Enfermedad
mensagial
pura
8 casos
CLASE III CLASE IV CLASE V
Glomerulonefr
itis
membranosa
Glomerulonefritis
proliferativa local
Glomerulonefri
tis proliferativa
difusa
4 casos88 casos25 casos
Evaluar la
severidad del LN
1. Lisis celular de glóbulos rojos
2. Lisis nuclear
3. Precipitación de ADN
4. Precipitación de proteínas
5. Almacenamiento de ADN
Amplificación
directa de un
gen o un
fragmento de
DNA
Incremento del
numero de copias de
una secuencia
particular de DNA
1. Desnaturalización
2. Hibridación con un
Primer
3. Síntesis por la DNA
polimerasa
TNF-α G
TNF-α A
INF-γ T
INF-γ A
ARMSSistema de mutación refractaria a la
amplificación
 Es un método ideal simple para detectar
cambios simples en las bases o pequeñas
delaciones
RESULTADOS
TNF-α
El polimorfismo se
detecto a 184Pb.
IFN-Y
El polimorfismo se
detecto a 263PB
Casos con LES mostraron aumento significativo de TNF-
Y IFN- plasmático en comparación con los controles
Debido a la alta
frecuencia de
genotipos
heterocigotos
los genotipos
homocigóticos no
mostraron diferencia
significativa
Author What they said Yes No
Guarniso-zuccardi et
al
Individuals that
carrying TNF-α -308ª,
risk allele were
significantly
associated with SLE in
European, South
American and Mexican
subjets but was not
associated with SLE in
Asian and African
subjects
X
Kim et al Analysis of the
relationship between
the IFN-Y +874 A>T
SNP and susceptibility
to SLE.
x
The polymorphisms in TNF-α and INF-Y genes
increase the susceptibility of individuals to acquire
systemic erythematosus lupus
 The polymorphisms in TNF-α and INF-Y genes doesn’t
generate alteration on the severity disease symptoms.
 There are factors like different ethnic origin, diverse
genetic and epigenetic interaction that could produce
changes in the results.
 The TNF-α and INF-Y could be a excellent
pharmacology target for the SLE treatment.
Systemic lupus Erythematosus

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Systemic lupus Erythematosus

  • 1. Juan José Cano Fernández Valeria Guerra Espinosa
  • 2. Recent researchs support the important role of the cytokine genes in autoimmune diseases, high serum levels of TNF-alfa and IFN- gamma wich are a very important pro- inflammatory citokines have been reported in SLE a complex disease that causes a high rate of mortality worldwide.
  • 3.  Is a prototypic autoinmune complex disease which is characterized by excessive production of autoantibodies against a broad range of self-antigens.  For SLE diagnosis, the patient must satisfy at least 4 criteria accordin to the SLE classification
  • 4.
  • 5. Polymorphism is the occurrence of two or more clearly different morphs or forms, also referred to as alternative phenotypes, in the population of a species.  Is the variation of a gene in a population
  • 6.  Is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
  • 7.  the regulation of immune cells  endogenous pyrogeninduce fever  apoptotic cell death  inflammation  inhibit tumorigenesis and  viral replication  respond to sepsis via IL1 & IL6
  • 8.  Interferon gamma is a cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon
  • 9.  innate and adaptive immunity against viral, bacterial and protozoal infections.  activator of macrophages and  inducer of Class II MHC
  • 11. This article is based on finding how the TNF-alfa and IFN-gamma are associated with immune factors especially in the systemic lupus erythematosus (SLE) and if this genes polymorphism could affect the susceptibility and severity of the diasease.
  • 12. •72 Mujeres •53 Hombres •23.4 ± 4.4 años 125 PACIENTES CON LES (LN) •66 Mujeres •46 Hombres •28.3± 6.2 años 112 PACIENTES SALUDABLES Centro de urología y nefrología, universidad Mansoura ,Egipto. Diagnostico de los pacientes: criterios de LES de la Universidad Americana de Reumatología 237 PACIENTES EN TOTAL
  • 13. CLASIFICACION DE LUPUS NEFRITICO CLASE I Glomérulo normal 0 casos CLASE II Enfermedad mensagial pura 8 casos CLASE III CLASE IV CLASE V Glomerulonefr itis membranosa Glomerulonefritis proliferativa local Glomerulonefri tis proliferativa difusa 4 casos88 casos25 casos Evaluar la severidad del LN
  • 14. 1. Lisis celular de glóbulos rojos 2. Lisis nuclear 3. Precipitación de ADN 4. Precipitación de proteínas 5. Almacenamiento de ADN
  • 15. Amplificación directa de un gen o un fragmento de DNA Incremento del numero de copias de una secuencia particular de DNA 1. Desnaturalización 2. Hibridación con un Primer 3. Síntesis por la DNA polimerasa TNF-α G TNF-α A INF-γ T INF-γ A
  • 16.
  • 17. ARMSSistema de mutación refractaria a la amplificación  Es un método ideal simple para detectar cambios simples en las bases o pequeñas delaciones
  • 21. Casos con LES mostraron aumento significativo de TNF- Y IFN- plasmático en comparación con los controles Debido a la alta frecuencia de genotipos heterocigotos los genotipos homocigóticos no mostraron diferencia significativa
  • 22. Author What they said Yes No Guarniso-zuccardi et al Individuals that carrying TNF-α -308ª, risk allele were significantly associated with SLE in European, South American and Mexican subjets but was not associated with SLE in Asian and African subjects X Kim et al Analysis of the relationship between the IFN-Y +874 A>T SNP and susceptibility to SLE. x
  • 23. The polymorphisms in TNF-α and INF-Y genes increase the susceptibility of individuals to acquire systemic erythematosus lupus  The polymorphisms in TNF-α and INF-Y genes doesn’t generate alteration on the severity disease symptoms.  There are factors like different ethnic origin, diverse genetic and epigenetic interaction that could produce changes in the results.  The TNF-α and INF-Y could be a excellent pharmacology target for the SLE treatment.

Editor's Notes

  1.  hibridación es el proceso de unir dos hebras complementarias de ADN.