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SAT0174 CCR5DELTA32 is associated with class IV nephritis in systemic lupus erythematosus
  1. J.S. Schauren1,
  2. T.D. Veit1,
  3. O.A. Monticielo2,
  4. R.M. Xavier2,
  5. J.C.T. Brenol2,
  6. J.A.B. Chies1
  1. 1Department of Genetics, Universidade Federal Do Rio Grande Do Sul
  2. 2Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that involves many organs and systems. CCR5 is an important chemokine receptor involved in inflammation. It is mainly expressed on the surface of cells that participate in the inflammatory process, such as lymphocytes and activated Th1 memory cells, monocytes, macrophages, dendritic cells and neutrophils. The CCR5 gene is located on chromosome 3p21.3-p24, and the CCR5Delta32 allelic variant generates a truncated protein that does not reach the cell surface, altering the response of these cells during inflammation.

Objectives To analyze the allelic and genotypic frequencies of the CCR5Delta32 polymorphism in systemic lupus erythematosus (SLE) patients from southern Brazil and to investigate a possible association of this allele variant with SLE susceptibility and clinical outcomes.

Methods We analyzed 367 SLE patients and 360 controls by PCR genotyping.

Results No association of this variant with susceptibility to SLE was observed. However, we observed that a majority of SLE patients diagnosed with nephritis that carried the CCR5Delta32 allele had been classified as class IV (67%). Patients carrying the CCR5Delta32 allele presented an odds ratio of 5.37 (1.77 – 15.25) for the development of class IV nephritis in relation to non-carrier patients. After stratifying by ethnic origin, African-derived carriers presented an odds ratio of 16.00 (1.87-188.93) in relation to non-carriers from the same ethnicity, whereas all European-derived patient carriers of the CCR5Δ32 allele who had biopsy proven nephritis had been classified as class IV. A multivariate analysis controlling the presence of the CCR5Delta32 allele, anti-DNAds antibodies, ethnicity, sex and age at diagnosis of SLE yielded a 2.96 times greater relative risk for a patient with the CCR5Delta32 allele to develop class IV nephritis in our cohort.

Conclusions Our data suggest that the CCR5Delta32 allele is an important modifier in SLE and could be considered a susceptibility factor to class IV nephritis, and that in African-derived, perhaps due to higher genetic susceptibility, this factor is more evident.

  1. Martens H.A., et al. Lack of association of C-C chemokine receptor 5 Δ32 deletion status with rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, and disease severity. J Rheumatol. 2010 Nov;37(11):2226-31.

  2. Martens H.A., et al. Role of CCR5 Delta32 bp deletion in RA and SLE. Autoimmunity. 2009 May;42(4):260-2.

  3. Mamtani M., et al. CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Ann Rheum Dis, 2008;67:1076-83.

  4. Aguilar F., et al. Chemokine receptor CCR2/CCR5 polymorphism in Spanish patients with systemic lupus erythematosus. J Rheumatol. 2003 Aug;30(8):1770-4.

Disclosure of Interest None Declared

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