Juan José Cano FernándezValeria 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.

INTRODUCTION

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

Systemic lupus Erythematosus :

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

Polymorphisms

TNF- α 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 pyrogeninduce fever apoptotic cell death inflammation inhibit viral replication respond to sepsis

Function

IFN-Y 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

Function

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.

OBJECTIVE

METODOS Y SUJETOS 125

PACIENTES CON LES (LN)

•72 Mujeres•53 Hombres•23.4 ± 4.4 años

112 PACIENTE

S SALUDAB

LES

•66 Mujeres •46 Hombres•28.3± 6.2 años

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

Glomerulonefritis

membranosa

Glomerulonefritis proliferativa

local

Glomerulonefritis

proliferativa difusa

4 casos 88 casos 25 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

EXTRACIÓN DE ADN

PCR- Reacción en cadena de la Polimerasa

Amplificación directa de un

gen o un fragmento de

DNA

Incremento del numero de copias de una secuencia particular de DNA

1. Desnaturalización2. Hibridación con un

Primer3. Síntesis por la DNA

polimerasa

TNF-α GTNF-α AINF-γ TINF-γ A

PCR- ARMS ARMSSistema de mutación refractaria a la

amplificación

Es un método ideal simple para detectar cambios simples en las bases o pequeñas

delaciones

RESULTADOS

TNF-αEl polimorfismo se detecto a 184Pb.

IFN-YEl 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.

CONCLUSSION