ORIGINAL_ARTICLE
Cytokines in systemic lupus erythematosus: their role in pathogenesis of disease and possible therapeutic opportunities
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may involve several organs. The disease is characterized by a recurring pattern of remission and flare. Immunologic factors seem to have important roles in the pathogenesis of SLE. Several studies revealed that cytokines are important in pathogenesis of this disorder. These cytokines include B cell activating factor (BAFF), tumor necrosis factor (TNF), interferon (IFN), interleukin (IL)-23, IL-17, IL-10, IL-6 and IL-21. In this article, the role of cytokines and their encoding genes are described and therapeutic applications have been discussed briefly.
https://www.rheumres.org/article_42357_44e8a30543382ef3b87319a33d50c4aa.pdf
2017-01-01
1
9
10.22631/rr.2017.69997.1010
Cytokines
immunologic factors
Pathogenesis
SLE
Systemic lupus erythematosus
Leili
Tahernia
mdlala_tn@yahoo.com
1
Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Shideh
Namazi
shidenamazi@gmail.com
2
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Nima
Rezaei
rezaei_nima@tums.ac.ir
3
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Vahid
Ziaee
ziaee@tums.ac.ir
4
Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
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64
ORIGINAL_ARTICLE
Autoantibody profile, disease activity and organ involvement in Iranian systemic lupus erythematosus patients
Autoantibodies have been implicated with increased risk of organ involvement in systemic lupus erythematosus (SLE). In the present study, we looked for autoantibody profiles and their association with clinical symptoms in a group of Iranian patients with SLE. In this study, 98 lupus patients (78 females and 20 males) were evaluated for the presence of autoantibodies against nRNP/Sm, Sm, SSA, Ro52, SSB, Scl-70, Jo-1, CENP B, nucleosomes, histones and Rib-P protein using immunoblotting technique. Anti-dsDNA was the most prevalent autoantibody (69.1%). The increased amount of autoantibodies, of the affected organs, and presence of anti-histone and anti-dsDNA correlated with disease activity. In the SLE patients with renal involvement, presence of anti-nucleosome (54.8% vs. 39.4%, P= 0.04) and decreased levels of anti-SSB (14.3% vs. 26.3%, P= 0.007) were significantly different campared with patients without renal involvement. Our results showed that elevated levels of autoantibodies including anti-dsDNA and anti-histone, and increasing number of involved organs, could be used as predictors for assessment of disease activity in patients with lupus. In addition, the increased levels of anti-nucleosome and the lower occurrence of anti-SSB could be used in the verification of renal damage.
https://www.rheumres.org/article_42358_b84ef7787a09e5ad4c75993027fd37f1.pdf
2017-01-01
11
16
10.22631/rr.2017.69997.1011
anti-dsDNA
autoantibody
organ involvement
Systemic lupus erythematosus
Mahmoud
Mahmoudi
mahmoudim@mums.ac.ir
1
Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Maryam
Rastin
rastinm@mums.ac.ir
2
Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Maryam
Sahebari
sahebarim@mums.ac.ir
3
Rheumatic Disease Research Center, Internal Medicine Department, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Shahrzad
Zamani
zamanish2@mums.ac.ir
4
Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Nafiseh
Tabasi
tabasin1@mums.ac.ir
5
Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Fu SM, Deshmukh US, Gaskin F. Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. J Autoimmun 2011; 37(2): 104-12. doi: 10.1016/j.jaut.2011.05.004.
1
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2
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4
Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349(16): 1526-33. doi: 10. 1056/NEJMoa021933.
5
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6
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7
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8
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9
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10
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11
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12
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13
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14
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15
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16
Cortes-Hernandez J, Ordi-Ros J, Labrador M, Bujan S, Balada E, Segarra A, et al. Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med 2004; 116(3): 165-73.
17
van der Vlag J, Berden JH. Lupus nephritis: role of antinucleosome autoantibodies. Semin Nephrol 2011; 31(4): 376-89. doi: 10.1016/j.semnephrol.2011.06.009.
18
Manson JJ, Ma A, Rogers P, Mason LJ, Berden JH, van der Vlag J, et al. Relationship between anti-dsDNA, anti-nucleosome and anti-alphaactin in antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res Ther 2009; 11(5): R154. doi: 10.1186/ar2831.
19
Gomez-Puerta JA, Burlingame RW, Cervera R. Anti-chromatin (antinucleosome) antibodies: diagnostic and clinical value. Autoimmun Rev 2008; 7(8):606–11. doi: 10.1016/j.autrev.2008.06. 005.
20
Solomon DH, Kavanaugh AJ, Schur PH, American College of Rheumatology Ad Hoc Committee on Immunologic Testing G. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002; 47(4): 434-44. doi: 10.1002/art.10561.
21
Shariati-Sarabi Z, Monzavi SM, Ranjbar A, Esmaily H, Etemadrezaie H. High disease activity is associated with high disease damage in an Iranian inception cohort of patients with lupus nephritis. Clin Exp Rheumatol 2013; 31(1):69-75.
22
Sherer Y, Gorstein A, Fritzler MJ, Shoenfeld Y. Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 2004; 34(2): 501-37.
23
Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol 2010; 125(2 Suppl 2): S238–47. doi: 10.1016/j.jaci.2009. 09.041.
24
Doria A, Zen M, Canova M, Bettio S, Bassi N, Nalotto L, et al. SLE diagnosis and treatment: when early is early. Autoimmun Rev 2010; 10(1): 55-60. doi: 10.1016/j.autrev. 2010.08.014.
25
Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000; 53(6): 424-32. Autoantibody profile and SLE
26
Olsen NJ, Yousif M, Mutwally A, Cory M, Elmagboul N, Karp DR. Organ damage in high-risk patients with systemic and incomplete lupus syndromes. Rheumatol Int 2013; 33(10): 2585-90. doi: 10.1007/s00296-013-2783-3.
27
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28
de Zubiria Salgado A, Herrera-Diaz C. Lupus nephritis: an overview of recent findings. Autoimmune Dis 2012; 2012:849684. doi: 10.1155/2012/849684.
29
ORIGINAL_ARTICLE
Prognostic factors of lupus nephritis in an Iranian population
Several studies have been done on Lupus Nephritis (LN) and the related outcomes, but there are limited data about the outcome of the disease in Iranian patients. Our aim of this study was to determine predictive factors of poor prognosis of LN amongst an Iranian population. This retrospective study included 111 LN patients, which were followed at least for one complete year according to their medical records. Data such as age, gender, geographical region, classification of renal biopsy, serum creatinine, blood pressure, complement levels, proteinuria, anti-dsDNA level, hemoglobin, Glomerular Filtration Rate (GFR) and serum albumin were collected. The short-term outcome was considered as complete remission, partial remission or non-remission; possible factors affecting the occurrence of these outcomes were evaluated. Pearson Chi-Square test and logistic regression were used for data analysis. A P value of less than 0.05 was considered statistically significant. Female: male ratio was 9.1:1 and the mean age of patients was 26.86±7 years. Low albumin, low GFR, low hemoglobin, high systolic and diastolic blood pressure, high serum creatinine, proteinuria and biopsy class IV at baseline were significantly associated with no remission or partial remission. There was no relationship between the mentioned outcomes and age, gender and geographic region of the subjects. All variables associated with the risk of non-remission should be considered in determining the prognosis and treatment plan. Of all the factors mentioned above, systolic blood pressure and low C3 levels had the highest correlation with the failure of remission.
https://www.rheumres.org/article_42359_ac0efb7c7abdd25ddab1b928338e1a66.pdf
2017-01-01
17
22
10.22631/rr.2017.69997.1012
lupus nephritis
Prognosis
remission
Hossein
Soleymani Salehabadi
1
Rheumatology Department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Hamidreza
Bashiri
hr.bashiri179@gmail.com
2
Rheumatology Department, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Nader
Nouri Majelan
dr_nori_majelan@yahoo.com
3
Nephrology Department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Ali
Dehghan
drdehghanali@yahoo.com
4
Rheumatology Department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Mohammadbagher
Owlia
5
Rheumatology Department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Vozmediano C, Rivera F, Lopez-Gomez JM, Hernandez D. Risk factors for renal failure in patients with lupus nephritis: data from the Spanish registry of glomerulonephritis. Nephron Extra 2012; 2(1): 269-77. doi: 10.1159/000342719.
1
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2
Saadati N, Haami M, BehroozAghdam A, Naghibzadeh B. Corrolation between clinical symptoms and renal pathology in patients with systemic lupus erythematosus (Persian). Med J Mashhad Univ Med Sci 55(2): 218-4.
3
Rajaee A, Behzadi S, Bazmi S, Moayeri M. The clinical and pathological findings among patients with lupus nephritis in Shiraz, Southern Iran. Shiraz E-Med J 2005; 6(1, 2): 2-7.
4
Barr RG, Seliger S, Appel GB, Zuniga R, D’Agati V,SalmonJ, et al. Prognosis in proliferative lupus nephritis: the role of socio-economic status and race/ethnicity. Nephrol Prognostic factors of lupus nephritis. Dial Transplant 2003; 18(10): 2039-46. doi: 10.1093/ndt/gfg345.
5
Hahn BH. Systemic Lupus Erythematosus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, editors. Harrison’s principles of internal medicine. 18 ed. USA: Mc Graw Hill companies; 2012. p. 2732.
6
Dhir V, Aggarwal A, Lawrence A, Agarwal V, Misra R. Long-term outcome of lupus nephritis in Asian Indians. Arthritis Care Res (Hoboken) 2012; 64(5): 713-20. doi: 10.1002/acr.21597.
7
Yokoyama H, Wada T, Hara A, Yamahana J, Nakaya I, Kobayashi M, et al. The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese. Kidney Int 2004; 66(6): 2382–8. doi: 10.1111/j.1523-1755.2004.66027.x.
8
Kotchen TA. Hypertensive vascular disease. In: Longo DL, Fauci AS, Kasper DL, Hauser S. L. editors. Harrison’s principles of internal medicine. 18 ed. USA: Mc Graw Hill companies; 2012. p. 2047.
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Adamson JW, Longo DL. Anemia and Polycythemia. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, editors. Harrison’s principles of internal medicine. 18 ed. USA: Mc Graw Hill companies; 2012. p. 450.
10
Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD. Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 2000; 35(5): 904-14.
11
Bargman JM, Skorecki K. Chronic kidney disease. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, editors. Harrison’s principles of internal medicine. 18 ed. USA: Mc Graw Hill companies; 2012. p. 2308.
12
Lewis JB, Neilson EG. Glomerulardisease. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, editors. Harrison’s principles of internal medicine. 18 ed. USA: Mc Graw Hill companies; 2012. p. 2337.
13
Lin J, Denker BM. Azotemia and urinary abnormalities. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, editors. Harrison’s principles of internal medicine. USA: Mc Graw Hill companies; 2012. p. 339.
14
Tesar V, Hruskova Z. Treatment of proliferative lupus nephritis: a slowly changing landscape. Nat Rev Nephrol 2011; 7(2): 96-109. doi: 10.1038/nrneph.2010.170.
15
Nezhad ST, Sepaskhah R. Correlation of clinical and pathological findings in patients with lupus nephritis: a five-year experience in Iran. Saudi J Kidney Dis Transpl 2008; 19(1): 32-40.
16
Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ, Collaborative Study G. Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 2008; 3(1): 46-53. doi: 10.2215/CJN.03280807.
17
Sircar D, Sircar G, Waikhom R, Raychowdhury A, Pandey R. Clinical features, epidemiology, and short-term outcomes of proliferative lupus nephritis in Eastern India. Indian J Nephrol 2013; 23(1): 5–11. doi: 10.4103/0971-4065.107187.
18
Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353(21): 2219-28. doi: 10.1056/NEJMoa043731.
19
Moroni G, Quaglini S, Gallelli B, Banfi G, Messa P, Ponticelli C. The long-term outcome of 93 patients with proliferative lupus nephritis.Nephrol Dial Transplant 2007; 22(9): 2531-9. doi: 10.1093/ndt/ gfm245.
20
Miranda-Hernandez D, Cruz-Reyes C, Angeles U, Jara LJ, Saavedra MA. Prognostic factors for treatment response in patients with lupus nephritis. Reumatol Clin 2014; 10(3):164-9. doi: 10.1016/ j. reuma.2013.08.001.
21
Korbet SM, Schwartz MM, Evans J, Lewis EJ, Collaborative Study G. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol 2007; 18(1): 244-54. doi: 10.1681/ASN. 2006090992.
22
Ghoreyshi FI. Prognosis in children with lupus nephritis. Med J Hormozgan Univ Med Sci 2005; 8(4): 193-7.
23
Croca SC, Rodrigues T, Isenberg DA. Assessment of a lupus nephritis cohort over a 30-year period. Rheumatology (Oxford) 2011; 50(8): 1424-30. doi: 10.1093/ rheumatology/ker101.
24
Kammoun K, Jarraya F, Bouhamed L, Kharrat M, Makni S, Hmida MB, et al. Poor prognostic factors of lupus nephritis. Saudi J Kidney Dis Transpl 2011; 22(4): 727-32.
25
Austin HA, Muenz LR, Joyce KM, Antonovych TT, Balow JE. Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome. Kidney International 1984; 25(4): 689-95. doi: 10.1038/ki.1984.75.
26
Birmingham DJ, Irshaid F, Nagaraja HN, Zou X, Tsao BP, Wu H, et al. The complex nature of serum C3 and C4 as biomarkers of lupus renal flare. Lupus 2010; 19(11): 1272–80. doi: 10.1177/0961203310371154.
27
ORIGINAL_ARTICLE
Osteoprotegerin (OPG) levels, total soluble receptor activator of nuclear factor-Kappa B ligand (total sRANKL) , and RANKL/OPG ratio in patients with rheumatoid arteritis
Rheumatoid arthritis (RA) is one of most important collagen vascular diseases. It has an unknown origin. The aim of this study was to evaluate circulating levels of osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-Kappa B ligand (total sRANKL), and RANKL/OPG ratio in patients with RA. Forty-five females with RA, who fulfilled the American college of rheumatology (ACR) criteria for RA were included in this cross-sectional study. The overall disease activity was evaluated by the disease activity score based on 28 joint counts (DAS-28). The OPG and sRANKL were measured by the enzyme-linked immunosorbent assays (ELISA). The levels of C-reactive protein (CRP) were measured by ELISA.We used Pearson’s correlation for our comparisons. There was no statistically significant difference between the levels of CRP, OPG, sRANKL and RANKL/OPG ratio in terms of DAS-28 grades in our patients. No significant correlation was found between the serum levels of OPG and DAS-28 (P= 0.525), duration of the disease (P= 0.884), Z-score of the femur (P= 0.546) and Z-score of the spine (P= 0.492), T-score of the femur (P= 0.137) and T-score of the spine (P= 0.821) in the patient group. No significant correlations were found between sRANKL levels with DAS-28 (0.919), Z-score of the femur (P= 0.971), Z-score of the spine (P= 0.832) and T-score of the femur (P = 0170) in the studied groups. Our study showed that there was no significant correlation between CRP, OPG, sRANKL and RANKL/OPG ratio in DAS-28 grading of our patients. For this reason they will not be used for evaluating disease activity. However, there was a significant difference between case and control groups except for sRANKL (pg/mL).
https://www.rheumres.org/article_42393_aca2618ff59b31faa2c5a79728fc130b.pdf
2017-01-01
23
29
10.22631/rr.2017.69997.1013
ACR criteria
OPG
Rheumatoid arthritis
sRANKL
Sousan
Kolahi
susan.kolahi@gmail.com
1
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Rheumatology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Amir
Ghorbanihaghjo
ghorbaniamir@hotmail.com
2
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Biochemistry, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Nadereh
Rashtchizadeh
rashtchizadeh@hotmail.com
3
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Biochemistry, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Alireza
Khabbazi
dr.khabazi@gmail.com
4
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Rheumatology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Mehrzad
Hajialilo
5
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Rheumatology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Hamid
Noshad
hamidnoshad1@yahoo.com
6
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Nephrology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
LEAD_AUTHOR
Farnaza
Boostani
farnazboostani1356@gmail.com
7
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Rheumatology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Mohaddeseh
Mokhtarkhani
m_mokhtarkhani@yahoo.com
8
Drug Applied Research Center, Connective Tissue Diseases Research Center, Department of Rheumatology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Carlsen H, Moskaug JO, Fromm SH, Blomhoff R. In vivo imaging of NFkappa B activity. J Immunol. 2002; 168(3):1441-6.
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2
Amaya-Amaya J, Sarmiento-Monroy JC, Mantilla RD, Pineda-Tamayo R, Rojas-Villarraga A, Anaya JM. Novel risk factors for cardiovascular disease in rheumatoid arthritis. Immunol Res. 2013; 56(2-3): 267-86. doi: 10.1007/s12026-013-8398-7.
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Rho YH, Chung CP, Oeser A, Solus J, Asanuma Y, Sokka T, et al. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum. 2009; 61(11): 1580-5. doi: 10.1002/art. 25009.
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Jorgensen C. Mesenchymal stem cells in arthritis: role of bone marrow microenvironment. Arthritis Res Ther. 2010; 12(4): 135. doi: 10.1186/ar3105.
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Leibbrandt A, Penninger JM. RANKL/RANK as key factors for osteoclast development and bone loss in arthropathies. Adv Exp Med Biol. 2009; 649: 100-13.
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Wada T, Nakashima T, Hiroshi N, Penninger JM. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2006; 12(1): 17-25. doi: 10.1016/j. molmed.2005.11.007.
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Fu Q, Jilka RL, Manolagas SC, O’Brien CA. Parathyroid hormone stimulates receptor activator of NFkappa B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein. J Biol Chem. 2002; 277(50): 48868-75. doi: 10.1074/jbc.M208494200.
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Spelling P, Bonfa E, Caparbo VF, Pereira RM. Osteoprotegerin/ RANKL system imbalance in active polyarticular-onset juvenile idiopathic arthritis: a bone damage biomarker?. Scand JRheumatol. 2008; 37(6): 439-44. doi: 10.1080/03009740802116224.
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Wasilewska A, Rybi-Szuminska AA, Zoch-Zwierz W. Serum osteoprotegrin (OPG) and receptor activator of nuclear factor kappaB (RANKL) in healthy children and adolescents. J Pediatr Endocrinol Metab. 2009; 22(12): 1099-104.
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Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3): 315-24.
21
Kiechl S, Werner P, Knoflach M, Furtner M, Willeit J, Schett G. The osteoprotegerin/ RANK/ RANKL system: a bone key to vascular disease. Expert Rev Cardiovasc Ther. 2006; 4(6): 801-11. doi: 10.1586/14779072.4. 6.801.
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Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994; 9(8): 1137-41. doi: 10.1002/jbmr.5650090802.
23
Klejna K, Naumnik B, Gasowska K, Mysliwiec M. OPG/ RANK/ RANKL signaling system and its significance in nephrology. Folia Histochem Cytobiol. 2009; 47(2): 199-206. doi: 10.2478/v10042-009-0035-x.
24
Gaudio A, Lasco A, Morabito N, Atteritano M, Vergara C, Catalano A, et al. Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role?. J Endocrinol Invest. 2005; 28(8): 677-82.
25
Hofbauer LC, Heufelder AE. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med (Berl). 2001; 79(5-6): 243-53.
26
Tat SK, Padrines M, Theoleyre S, Couillaud-Battaglia S, Heymann D, Redini F, et al. OPG/ membranous–RANKL complex is internalized via the clathrin pathway before a lysosomal and a Kolahi et al.proteasomal degradation. Bone. 2006; 39(4): 706-15. doi: 10.1016/j.bone.2006.03.016.
27
Nakamura H, Kumei Y, Morita S, Shimokawa H, Ohya K, Shinomiya K. Suppression of osteoblastic phenotypes and modulation of pro- and anti-apoptotic features in normal human osteoblastic cells under a vector-averaged gravity condition. J Med Dent Sci. 2003; 50(2): 167-76.
28
Kobayashi-Sakamoto M, Hirose K, Nishikata M, Isogai E, Chiba I. Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases. FEMS Microbiol Lett. 2006; 264(2): 238-45. doi: 10.1111/j.1574-6968.2006.00458.x.
29
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31
Anand DV, Lim E, Darko D, Bassett P, Hopkins D, Lipkin D, et al. Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/ vascular calcification markers. J Am Coll Cardiol. 2007; 50(23): 2218-25. doi: 10.1016/j.jacc. 2007.08.032.
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Ziolkowska M, Kurowska M, Radzikowska A, Luszczykiewicz G, Wiland P, Dziewczopolski W, et al. High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment. Arthritis Rheum. 2002; 46(7): 1744-53. doi: 10.1002/art.10388.
34
Gonzalez-Alvaro I, Ortiz AM, Tomero EG, Balsa A, Orte J, Laffon A, et al. Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNFantagonists. Ann Rheum Dis. 2007; 66(12): 1675-8. doi: 10.1136/ard.2007.071910.
35
Xu S, Wang Y, Lu J, Xu J. Osteoprotegerin and RANKL in the pathogenesis of rheumatoid arthritis-induced osteoporosis. Rheumatol Int. 2012; 32(11): 3397-403. doi: 10.1007/s00296-011-2175-5.
36
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37
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38
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39
ORIGINAL_ARTICLE
Gene expression profile of proinflammatory cytokines in Iranian patients with ankylosing spondylitis
Ankylosing spondylitis (AS) is mostly characterized by inflammation of the sacroiliac joints, enthesis and the spine. This study aims to determine gene expression profile of proinflammatory cytokines and their correlations with disease activity, spinal mobility, functional status, quality of life, and smoking in Iranian patients with ankylosing spondylitis. Peripheral blood mononuclear cells (PBMCs) were isolated from 48 patients with AS and 47 age and gender-matched healthy controls; then total RNA content of leukocytes was extracted, followed by cDNA synthesis from the mRNA of PBMCs. Quantitative polymerase chain reaction was performed to measure mRNA expression of TNF-α, IL-1β and IFN-γ genes. Clinical characteristics were evaluated and their correlations were analyzed with gene expression levels of the prionflammatory cytokines. A significant overexpression of TNF-α was observed in the patient group, but there was no significant difference in expression of other cytokines between groups. A positive correlation (P< 0.01) between TNF-α and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and negative correlation (P< 0.05) between IFN-γ and Bath Ankylosing Spondylitis Functional Index (BASFI) were found. Eta-Squared test supported significant results about the smoking effect on Bath Ankylosing Spondylitis Metrology Index (BASMI) (P< 0.05) and IFN-γ (P< 0.01). Our results demonstrated that TNF-α was the most important cytokine responsible for inflammatory-related outcomes of AS in the Iranian population.
https://www.rheumres.org/article_42394_f23017e680a68453b5ce110125005ed8.pdf
2017-01-01
31
38
10.22631/rr.2017.69997.1014
ankylosing spondylitis
Proinflammatory cytokines
Gene expression
Mahsa
Asadbeik
mahsa_asadbeik@yahoo.com
1
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Ali
Farazmand
afarazmand@khayam.ut.ac.ir
2
Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran
AUTHOR
Negar
Vanaki
nvnegarin@gmail.com
3
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Shayan
Mostafaei
mostafa.shayan@modares.ac.ir
4
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Ahmad Reza
Jamshidi
5
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Nooshin
Ahmadzadeh
nahmadzade@yahoo.com
6
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Mahdi
Vojdanian
vojdanian@gmail.com
7
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Mahsa
Mohammad–Amoli
8
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Mahdi
Mahmoudi
mahmoudim@tums.ac.ir
9
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Stolwijk C, van Onna M, Boonen A, van Tubergen A. Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res (Hoboken). 2015 doi: 10.1002/acr.22831.
1
Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol. 2010; 6(7): 399-405. doi: 10.1038/nrrheum.2010.79.
2
Zambrano-Zaragoza JF, Agraz-Cibrian JM, Gonzalez-Reyes C, Duran-Avelar Mde J, Vibanco-Perez N. Ankylosing spondylitis: from cells to genes. Int J Inflam. 2013; 501653. doi: 10.1155/2013/ 501653.
3
Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973; 1(7809): 904-7.
4
Tsui FW, Tsui HW, Akram A, Haroon N, Inman RD. The genetic basis of ankylosingspondylitis: new insights into disease pathogenesis. Appl Clin Genet. 2014; 7: 105-15. doi: 10.2147/TACG.S37325.
5
Reveille JD, Sims AM, Danoy P, Evans DM, Leo P, Pointon JJ, et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010; 42(2): 123-7. doi: 10.1038/ng.513.
6
Hreggvidsdottir HS, Noordenbos T, Baeten DL. Inflammatory pathways in spondyloarthritis. Mol Immunol. 2014; 57(1): 28-37. doi: 10.1016/j.molimm.2013. 07.016.
7
Keller C, Webb A, Davis J. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann Rheum Dis. 2003; 62(12): 1128-32.
8
Colbert RA, Tran TM, Layh-Schmitt G. HLA-B27 misfolding and ankylosing spondylitis. MolImmunol. 2014; 57(1): 44-51. doi: 10.1016/j.molimm.2013.07. 013.
9
Cui X, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng W, et al. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest. 2002; 110(4): 515-26. doi: 10.1172/JCI13847.
10
Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science. 2002; 296(5573): 1634-5. doi: 10.1126/science.1071924.
11
Chen X, Wu X, Zhou Q, Howard OM, Netea MG, Oppenheim JJ. TNFR2 is critical for the stabilization of the CD4+Foxp3+regulatory T. cell phenotype in the inflammatory environment. J Immunol. 2013; 190(3): 1076–84. doi: 10.4049/ jimmunol.1202659.
12
Mansour M, Cheema GS, Naguwa SM, Greenspan A, Borchers AT, Keen CL, et al. Asadbeik et al.Ankylosing spondylitis: a contemporary perspective on diagnosis and treatment. Semin Arthritis Rheum. 2007; 36(4): 210-23. doi: 10.1016/j.semarthrit. 2006.08.003.
13
Nicknam MH, Mahmoudi M, Amirzargar AA, Jamshidi AR, Rezaei N, Nikbin B. HLA-B27 subtypes and tumor necrosis factor alpha promoter region polymorphism in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw. 2009; 20(1):17-20. doi: 10.1684/ecn.2009.0143.
14
Ji Y, Yang X, Yang L, Wu D, Hua F, Lu T, et al. Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis. Cell Biochem Biophys. 2013; 67(3): 915–22. doi: 10.1007/s12013-013-9582-z.
15
Li B, Wang P, Li H. The association between TNF-alpha promoter polymorphisms and ankylosing spondylitis: a meta-analysis. Clin Rheumatol. 2010; 29(9): 983-90. doi: 10.1007/s10067-010-1499-y.
16
Chung WT, Choe JY, Jang WC, Park SM, Ahn YC, Yoon IK, et al. Polymorphisms of tumor necrosis factor-alpha promoter region for susceptibility to HLA-B27-positive ankylosing spondylitis in Korean population. Rheumatol Int. 2011; 31(9): 1167-75. doi: 10.1007/s00296-010-1434-1.
17
Vazquez-Del Mercado M, Garcia-Gonzalez A, Munoz-Valle JF, Garcia-Iglesias T, Martinez-Bonilla G, Bernard-Medina G, et al. Interleukin 1beta (IL-1beta), IL-10, tumor necrosis factor-alpha, and cellular proliferation index in peripheral blood mononuclear cells in patients with ankylosing spondylitis. J Rheumatol. 2002; 29(3): 522-6.
18
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family–Balance between agonists and antagonists in inflammatory diseases. Cytokine. 2015; 76(1): 25-37. doi: 10.1016/j.cyto.2015. 06.017.20.
19
Mahmoudi M, Amirzargar AA, Jamshidi AR, Farhadi E, Noori S, Avraee M, et al. Association ofIL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw. 2011; 22(4): 175-80. doi: 10.1684/ecn.2011.0293.
20
Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Crossregulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci U S A. 2005; 102(9): 3372-7. doi: 10.1073/ pnas.0408506102.
21
Feng Y, Ding J, Fan CM, Zhu P. Interferon-gamma contributes to HLAB27-associated unfolded protein response in spondyloarthropathies. J Rheumatol. 2012; 39(3): 574-82. doi: 10.3899/jrheum.101257.
22
Moll JM,Wright V. New York clinical criteria for ankylosing spondylitis. A statistical evaluation. Ann Rheum Dis. 1973; 32(4): 354-63.
23
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ORIGINAL_ARTICLE
Autoimmune polyendocrine syndrome type IIIC and ankylosing spondylitis: a case report
Autoimmune polyendocrine syndrome (APS) is an autoimmune disorder defined by multiple endocrinopathies and the presence of other systemic or organ-specific autoimmunities. This case study, reports on a 46-year-old woman with confirmed idiopathic hyperparathyroidism, who was referred for inflammatory back pain. HLA-B27 positivity, recurrent anterior uveitis and radiologic findings led to ankylosing spondylitis (AS) diagnosis. By further investigations, a subclinical atrophic autoimmune thyroid disease (AITD) was also diagnosed for her in addition to a history of premature ovarian failure. According to the absence of adrenal insufficiency in addition to an AITD and systemic autoimmune disorder, APS type IIIC was the most probable diagnosis. To the best of our knowledge, this is the first case report of APS type III associated with AS.
https://www.rheumres.org/article_42396_83447e52439cd2398bf4bfe479e84f7a.pdf
2017-01-01
39
43
10.22631/rr.2017.69997.1015
ankylosing
autoimmune
Hashimoto disease
hypoparathyroidism
polyendocrinopathies
primary ovarian insufficiency
spondylitis
Ali
Javinani
a-javinani@student.tums.ac.ir
1
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Hamid Reza
Aghaei Meybodi
hraghaei@tums.ac.ir
2
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Ahmad Reza
Jamshidi
3
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Farhad
Gharibdoost
f_gharibdoost@hotmail.com
4
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Hoda
Kavosi
hodakavosi@yahoo.com
5
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Cutolo M. Autoimmune polyendocrine syndromes. Autoimmun Rev. 2014; 13(2): 85-9. doi:10.1016/j.autrev.2013.07.006.
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