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A study on the association of autoantibodies, chemokine, and its receptor with disease activity in systemic lupus erythematosus in North Indian population

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Abstract

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by the production of autoantibodies against a spectrum of nuclear antigens. RANTES and its receptor CCR5 have been associated with the pathogenesis of SLE. The objective of this study is to analyze autoantibodies (DNA/RNA), allelic distribution of RANTES and the association of levels of RANTES and its receptor CCR5 in SLE patients in North Indian region. The RANTES-403 and RANTES-28 polymorphism in the promoter region of RANTES gene was studied in 80 patients and 80 healthy controls. The levels of chemokine RANTES, its receptor CCR5, anti-dsDNA, and anti-SSA antibodies levels were determined. Disease activity was assessed with the systemic lupus erythematosus disease activity index (SLEDAI) score. All the parameters were studied for statistical analysis by using t test (graph pad prism) and correlation by SPSS data. PCR–RFLP performed showed 28C/C and the 403G/G genotypes in both patients and controls, but no other genotypes such as 28C/G, 28G/G and 403A/G, 403A/A were found. Patients had higher levels of RANTES (1840.48 ± 739.42 vs. 835.44 ± 70.48 pg/ml; P < 0.0001) and its receptor CCR5 expression (26.49 ± 0.16 vs. 24.72 ± 3.02 %; P < 0.05) compared to controls. The levels of autoantibodies anti-dsDNA and anti-SSA were also higher in patients than controls. The patients showing elevated anti-dsDNA had negative correlation with SLEDAI score (P < 0.05) while borderline patients were not found to be correlated. In case of anti-Ro/anti-SSA antibody levels, the borderline patients showed a moderately significant negative correlation as compared to controls than patients with elevated autoantibody (P < 0.01). The levels of RANTES and CCR5 were also higher in case of patients than controls. But there was no significant correlation of RANTES and CCR5 with disease activity. We were unable to find an association of RANTES polymorphism with SLE in North Indian population in our sample. No significant difference in allele distribution of RANTES-28 and RANTES-403 in the sample of 160 individuals was detected. Of the two autoantibodies studied, anti-Ro/anti-SSA levels in borderline lupus patients appeared as an important parameter for monitoring/diagnosis of lupus patients.

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References

  1. Wallace DJ, Hahn BJ (1997) The clinical presentation of systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds) Dubois’ lupus erythematosus, 5th edn. Williams & Wilkins, Baltimore, p 627

  2. Dieker JW, van der Vlag J, Berden JH (2002) Triggers for anti-chromatin autoantibody production in SLE. Lupus 11(12):856–864

    Article  PubMed  CAS  Google Scholar 

  3. Lindqvist AK, Steinsson K, Johanneson B, Kristjansdottir H, Arnasson A, Grondal G, Jonasson I, Magnusson V, Sturfelt G, Truedsson L, Svenungsson E, Lundberg I, Terwilliger JD, Gyllensten UB, Alarcon-Riquelme ME (2000) A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun 14(2):169–178. doi:10.1006/jaut.1999.0357

    Article  PubMed  CAS  Google Scholar 

  4. Eriksson C, Eneslatt K, Ivanoff J, Rantapaa-Dahlqvist S, Sundqvist KG (2003) Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus. Lupus 12(10):766–774

    Article  PubMed  CAS  Google Scholar 

  5. Tsukahara T, Makino Y, Fujii T, Ogawa M, Saisho H, Hamano Y, Ueda S, Akikusa B, Danoff TM (2002) Role of RANTES in the development of autoimmune tissue injuries in MRL-Fas lpr mice. Clin Immunol 103(1):89–97. doi:10.1006/clim.2001.5198

    Article  PubMed  CAS  Google Scholar 

  6. Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM (1992) Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med 176(2):587–592

    Article  PubMed  CAS  Google Scholar 

  7. Vila LM, Molina MJ, Mayor AM, Cruz JJ, Rios-Olivares E, Rios Z (2007) Association of serum MIP-1alpha, MIP-1beta, and RANTES with clinical manifestations, disease activity, and damage accrual in systemic lupus erythematosus. Clin Rheumatol 26(5):718–722. doi:10.1007/s10067-006-0387-y

    Article  PubMed  Google Scholar 

  8. Anders HJ, Vielhauer V, Kretzler M, Cohen CD, Segerer S, Luckow B, Weller L, Grone HJ, Schlondorff D (2001) Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. J Am Soc Nephrol 12(5):919–931

    PubMed  CAS  Google Scholar 

  9. Tian S, Li J, Wang L, Liu T, Liu H, Cheng G, Liu D, Deng Y, Gou R, Wan Y, Jia J, Chen C (2007) Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare. Inflamm Res 56(7):304–310. doi:10.1007/s00011-007-6147-x

    Article  PubMed  CAS  Google Scholar 

  10. Stasikowska O, Danilewicz M, Wagrowska-Danilewicz M (2007) The significant role of RANTES and CCR5 in progressive tubulointerstitial lesions in lupus nephropathy. Pol J Pathol 58(1):35–40

    PubMed  CAS  Google Scholar 

  11. Lloyd CM, Dorf ME, Proudfoot A, Salant DJ, Gutierrez-Ramos JC (1997) Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis. J Leukoc Biol 62(5):676–680

    PubMed  CAS  Google Scholar 

  12. Furuichi K, Wada T, Sakai N, Iwata Y, Yoshimoto K, Shimizu M, Kobayashi K, Takasawa K, Kida H, Takeda SI, Mukaida N, Matsushima K, Yokoyama H (2000) Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases. Am J Nephrol 20(4):291–299. doi:13603

    Article  PubMed  CAS  Google Scholar 

  13. Nelson PJ, Kim HT, Manning WC, Goralski TJ, Krensky AM (1993) Genomic organization and transcriptional regulation of the RANTES chemokine gene. J Immunol 151(5):2601–2612

    PubMed  CAS  Google Scholar 

  14. Liu H, Chao D, Nakayama EE, Taguchi H, Goto M, Xin X, Takamatsu JK, Saito H, Ishikawa Y, Akaza T, Juji T, Takebe Y, Ohishi T, Fukutake K, Maruyama Y, Yashiki S, Sonoda S, Nakamura T, Nagai Y, Iwamoto A, Shioda T (1999) Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci USA 96(8):4581–4585

    Article  PubMed  CAS  Google Scholar 

  15. Ye DQ, Yang SG, Li XP, Hu YS, Yin J, Zhang GQ, Liu HH, Wang Q, Zhang KC, Dong MX, Zhang XJ (2005) Polymorphisms in the promoter region of RANTES in Han Chinese and their relationship with systemic lupus erythematosus. Arch Dermatol Res 297(3):108–113. doi:10.1007/s00403-005-0581-9

    Article  PubMed  CAS  Google Scholar 

  16. Hassan AB, Lundberg IE, Isenberg D, Wahren-Herlenius M (2002) Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with clinical disease activity in patients with systemic lupus erythematosus. Scand J Rheumatol 31(3):133–139

    PubMed  Google Scholar 

  17. Praprotnik S, Bozic B, Kveder T, Rozman B (1999) Fluctuation of anti-Ro/SS-A antibody levels in patients with systemic lupus erythematosus and Sjogren’s syndrome: a prospective study. Clin Exp Rheumatol 17(1):63–68

    PubMed  CAS  Google Scholar 

  18. Franceschini F, Cavazzana I (2005) Anti-Ro/SSA and La/SSB antibodies. Autoimmunity 38(1):55–63. doi:10.1080/08916930400022954

    Article  PubMed  CAS  Google Scholar 

  19. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349(16):1526–1533. doi:10.1056/NEJMoa021933

    Article  PubMed  CAS  Google Scholar 

  20. Ahlin E, Mathsson L, Eloranta ML, Jonsdottir T, Gunnarsson I, Ronnblom L, Ronnelid J (2012) Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE. Lupus 21(6):586–595. doi:10.1177/0961203311434938

    Article  PubMed  CAS  Google Scholar 

  21. Yoshimi R, Ueda A, Ozato K, Ishigatsubo Y (2012) Clinical and pathological roles of Ro/SSA autoantibody system. Clin Dev Immunol 2012:606195. doi:10.1155/2012/606195

    Article  PubMed  Google Scholar 

  22. Lindop R, Arentz G, Thurgood LA, Reed JH, Jackson MW, Gordon TP (2012) Pathogenicity and proteomic signatures of autoantibodies to Ro and La. Immunol Cell Biol 90(3):304–309. doi:10.1038/icb.2011.108

    Article  PubMed  CAS  Google Scholar 

  23. Izmirly PM, Saxena A, Kim MY, Wang D, Sahl SK, Llanos C, Friedman D, Buyon JP (2011) Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 124(18):1927–1935. doi:10.1161/circulationaha.111.033894

    Article  PubMed  Google Scholar 

  24. Gade-Andavolu R, Comings DE, MacMurray J, Vuthoori RK, Tourtellotte WW, Nagra RM, Cone LA (2004) RANTES: a genetic risk marker for multiple sclerosis. Mult Scler 10(5):536–539

    Article  PubMed  CAS  Google Scholar 

  25. Ye D (2001) Dermatosis epidemiology. The People Health Publishing House, Beijing

    Google Scholar 

  26. Aguilar F, Nunez-Roldan A, Torres B, Wichmann I, Sanchez-Roman J, Gonzalez-Escribano MF (2003) Chemokine receptor CCR2/CCR5 polymorphism in Spanish patients with systemic lupus erythematosus. J Rheumatol 30(8):1770–1774

    PubMed  CAS  Google Scholar 

  27. Magnusson V, Lindqvist AK, Castillejo-Lopez C, Kristjansdottir H, Steinsson K, Grondal G, Sturfelt G, Truedsson L, Svenungsson E, Lundberg I, Gunnarsson I, Bolstad AI, Haga HJ, Jonsson R, Klareskog L, Alcocer-Varela J, Alarcon-Segovia D, Terwilliger JD, Gyllensten UB, Alarcon-Riquelme ME (2000) Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus. Genomics 70(3):307–314. doi:10.1006/geno.2000.6374

    Article  PubMed  CAS  Google Scholar 

  28. Akalin E, Murphy B (2001) Gene polymorphisms and transplantation. Curr Opin Immunol 13(5):572–576

    Article  PubMed  CAS  Google Scholar 

  29. Kelley VR, Rovin BH (2003) Chemokines: therapeutic targets for autoimmune and inflammatory renal disease. Springer Semin Immunopathol 24(4):411–421. doi:10.1007/s00281-003-0124-4

    Article  PubMed  Google Scholar 

  30. Lian LH, Kee BP, Ng HL, Chua KH (2011) Lack of association between RANTES-28, SDF-1 gene polymorphisms and systemic lupus erythematosus in the Malaysian population. Genet Mol Res 10(4):2841–2850. doi:10.4238/2011.November.17.2

    Article  PubMed  CAS  Google Scholar 

  31. Xu WD, Peng H, Zhou M, Zhang M, Li BZ, Pan HF, Ye DQ (2013) Association of RANTES and MBL gene polymorphisms with systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 40(2):941–948. doi:10.1007/s11033-012-2135-5

    Article  PubMed  CAS  Google Scholar 

  32. Wada T, Furuichi K, Segawa-Takaeda C, Shimizu M, Sakai N, Takeda SI, Takasawa K, Kida H, Kobayashi KI, Mukaida N, Ohmoto Y, Matsushima K, Yokoyama H (1999) MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis. Kidney Int 56(3):995–1003. doi:10.1046/j.1523-1755.1999.00646.x

    Article  PubMed  CAS  Google Scholar 

  33. Lu MM, Wang J, Pan HF, Chen GM, Li J, Cen H, Feng CC, Ye DQ (2012) Increased serum RANTES in patients with systemic lupus erythematosus. Rheumatol Int 32(5):1231–1233. doi:10.1007/s00296-010-1761-2

    Article  PubMed  CAS  Google Scholar 

  34. Shah D, Wanchu A, Bhatnagar A (2011) Interaction between oxidative stress and chemokines: possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis. Immunobiology 216(9):1010–1017. doi:10.1016/j.imbio.2011.04.001

    Article  PubMed  CAS  Google Scholar 

  35. Gao HCS, Burkly LC, Jarchun I, Banas B, Schlondorff D et al (2006) TNF-like weak inducer of apoptosis (TWEAK) stimulates human kidney cells to elaborate chemokines central to the pathogenesis of lupus nephritis. Paper presented at the 2006 annual scientific meeting

  36. Al-Saleh J, el-Eissawy S (2006) The role of T helper cell subsets in pathogenesis of systemic lupus erythematosus and their relation to disease activity. Egypt J Immunol 13(2):41–48

    PubMed  Google Scholar 

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Acknowledgments

We thank the patients and healthy donors for their cooperation in donating blood samples. This work was supported by University Grant Commission, New Delhi, India, Grant No. F.No.33-228/2007.

Conflict of interest

We have no conflicts of interest in the authorship and publication of this article.

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Authors and Affiliations

  1. Department of Biochemistry, Basic Medical Sciences Block, Punjab University, Chandigarh, 160014, India

    Leishangthem Bidyalaxmi Devi & Archana Bhatnagar

  2. Division of Arthritis and Rheumatic Diseases-OP09, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Ajay Wanchu

  3. Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Aman Sharma

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  1. Leishangthem Bidyalaxmi Devi
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Correspondence to Archana Bhatnagar.

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Bidyalaxmi Devi, L., Bhatnagar, A., Wanchu, A. et al. A study on the association of autoantibodies, chemokine, and its receptor with disease activity in systemic lupus erythematosus in North Indian population. Rheumatol Int 33, 2819–2826 (2013). https://doi.org/10.1007/s00296-013-2812-2

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