The chemokine receptor CCR5 genetic polymorphism and expression in rheumatoid arthritis patients.
OBJECTIVE
To identify the genetic polymorphism of the chemokine receptor CCR5 (the Delta32 allelic variant) in patients with rheumatoid arthritis (RA) and compare the findings with healthy controls. To compare the CCR5 phenotypic expression in T cells and monocytes isolated from the peripheral blood and synovial fluid in a subgroup of RA patients.


METHODS
CCR5 genes of 92 RA patients and 160 healthy controls were genotyped using specific primers flanking the region of deletion. The ethnic distribution was similar between the groups. Flow cytometric analysis was used for immunophenotyping the T cells and monocytes isolated from the peripheral blood and synovial fluid of eight RA patients. The isolated cells were triple stained with CD4 or CD8, CD25 and CCR5 monoclonal antibodies.


RESULTS
There was no difference in the CCR5Delta32 genotypic frequency between the RA patients and the control group (0.055 and 0.063, respectively, p = 0.989). No homozygote for the CCR5Delta32 allele was seen in either group. Five heterozygotes were identified in the RA patient group, whose disease was shown to be aggressive. A significant enrichment of activated CCR5+ monocytes was seen in the synovial fluid of the RA patients subjected to arthrocentesis, who were all homozygotes for the CCR5 wild-type genotype.


CONCLUSIONS
A protective role for the CCR5 allelic variant in RA development was not observed. Disease severity in the heterozygotes suggests that other proinflammatory mechanisms might overcome this mutation in vivo. The activated CCR5+ monocyte enrichment in the rheumatoid synovial fluid might indicate that this cell population has an important role in the pathogenesis of the disease.
Kohem
C L
CL
Rheumatic Diseases Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. charleskohem@brturbo.com.br
Brenol
J C T
JC
Xavier
R M
RM
Bredemeier
M
M
Brenol
C V
CV
Dedavid e Silva
T L
TL
de Castilhos Mello
A
A
Cañedo
A D
AD
Neves
A G
AG
Chies
J A B
JA
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005006:Ethnicity; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D019713:Receptors, CCR5; D004247:DNA