Association of rheumatoid arthritis with a functional chemokine receptor, CCR5

Abstract

Objective. To investigate whether the pathogene-sis of rheumatoid arthritis (RA) is associated with the functional chemokine receptor CCR5, which is the primary CC chemokine receptor expressed by T cells in rheumatoid synovium, and its nonfunctional receptor, 32CCR5, which is generated by the homozygous 32-basepair deletion (32) in the CCR5 gene. Methods. The frequency of the CCR5 genotype was compared among 673 patients with RA, 113 patients with systemic lupus erythematosus (SLE), and 815 control subjects. The CCR5 genotype was studied by polymerase chain reaction amplification of the region flanking the 32 deletion (32CCR5). Results. Frequencies of the wild-type CCR5 alleles (0.929, 0.907, and 0.942, respectively) and 32CCR5 alleles (0.071, 0.093, and 0.058, respectively) in controls, SLE patients, and RA patients did not differ significantly. However, none of the RA patients had the homozygous 32CCR5 genotype, compared with a frequency of 0.009 in controls (P 0.014 by Fisher's exact test; 2 4.12 with Yates' correction, P 0.042) and 0.027 in SLE patients (P 0.003 by Fisher's exact test; 2 11.63 with Yates' correction, P 0.0006). Conclusion. The results suggest that the CCR5 receptor plays an important role in RA and may be a suitable target for therapy.

Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non‐obese diabetic mice

“…T cell activation is thus characterized by increased CCR5 expression, which is associated with diabetes and possibly with other autoimmune diseases. Indeed, CCR5 association is reported in autoimmune diseases such as rheumatoid arthritis [19,20] and multiple sclerosis, in which an increase in CCR5 + cells has been detected [21].…”

TNF-α-Induced Secretion of C-C Chemokines Modulates C-C Chemokine Receptor 5 Expression on Peripheral Blood Lymphocytes

“…Studies on individuals with a variable CCR5 genotype revealed clinical amelioration in RA. In cases in which heterozygosity of the ⌬32 mutation occurred, the patients lacked rheumatoid factor, and the swelling of the joints was decreased compared with wild-type individuals (68,69). In this case, migration to the site of inflammation was reduced.…”

CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis

“…21 CCR5 is a coreceptor for the M-tropic strain of human immunodeficiency virus (HIV) and as a result CCR5-D32 homozygotes are afforded complete immunity from this strain, while heterozygotes show resistance to infection and a delay in the onset of acquired immunodeficiency syndrome (AIDS) compared to the wild-type counterparts. [22][23][24][25] In chronic inflammatory disorders, the CCR5-D32 mutation shows a negative association with rheumatoid arthritis, 26 which in turn is associated with a predominantly Th1 immune response. In patients with multiple sclerosis, the mutation is associated with a delayed age of onset of the disease and a lower risk of recurrent clinical disease activity.…”