Printer Friendly

Effects of B-lymphocyte dysfunction on the serum copper selenium and zinc levels of rheumatoid arthritis patients.

Byline: Jiangtao Li Yan Liang Hejuan Mao Wenyu Deng and Jie Zhang

ABSTRACT

Objective: To study the effects of B-lymphocyte dysfunction on the serum copper selenium and zinc levels of rheumatoid arthritis (RA) patients and to provide evidence for clinical practice.

Methods: Sixty RA patients enrolled in our hospital from August 2009 to August 2013 were selected as the observation group. Another 60 healthy subjects who received physical examinations in our hospital were selected as the control group. Their B-lymphocyte stimulator (BlyS) levels and CD19+CD25+ lymphocyte percentages were determined. The levels of trace elements were measured and correlation analysis was performed.

Results: The BlyS levels of the observation group and the control group were (0.390.21) ng/ml and (0.130.04) ng/ml respectively which were significantly different (P less than 0.05). The percentages of CD25+ CD19+ and CD19+CD25+ lymphocytes in the observation group were significantly higher than those in the control group (P less than 0.05). The serum copper selenium and zinc levels of the observation group were significantly lower than those of the control group (P less than 0.05). Pearson's correlation analysis showed that the BlyS level was correlated with the levels of copper selenium and zinc respectively (r=-0.541 -0.370 -0.430 P less than 0.05).

Conclusion: Rheumatoid Arthritis may be induced by BlyS-mediated B-lymphocyte dysplasia and dysfunction accompanied by decreased expressions of copper selenium and zinc.

KEY WORDS: B-lymphocyte Rheumatoid arthritis Dysfunction Trace element.

INTRODUCTION

Rheumatoid arthritis (RA) is an autoimmune disease characteristic in synovitis as well as progressive destructions of cartilage and bone. As one of the main disabling diseases in China its prevalence rate has reached 1.2%.1 Despite of unclear etiology and pathogenesis RA is generally associated with genetic and environmental factors and autoimmune response.23 B-lymphocyte stimulator (BlyS) which participates in the proliferation and differentiation of B-cells plays an importance role in humoral immunity.45 RA is commonly accompanied by B-lymphocyte dysfunction which is mainly manifested as evident increase and high activation of CD19+CD25+ lymphocytes that reflect the disease progress.6

It is well known that trace elements are closely associated with many aspects of human life such as tissue construction and repair immune function enhancement and even prevention and treatment of RA. As en essential trace element copper is a crucial component of human proteins and enzymes.7 Being accountable for approximately 0.033 of body mass zinc is widely involved in many metabolism processes. Selenium can resist oxidation boost the immune system and promote human development and growth etc.89 Therefore the effects of B-lymphocyte dysfunction on the serum copper selenium and zinc levels of RA patients were studied herein to provide evidence for clinical practice.

METHODS

Subjects: Observation group: Sixty RA patients enrolled in our hospital from August 2009 to August 2013 were selected. They were all older than 16 and were diagnosed conforming with the Classification Criteria for Rheumatic Diseases stipulated by American College of Rheumatology in 1987. As first-visit patients they had not taken slow-acting antirheumatic drugs such as methotrexate and sulfasalazine or biologics. They were not complicated with other autoimmune diseases cardiovascular and cerebrovascular diseases metabolic diseases infectious diseases or liver and kidney diseases. The observation group comprised 32 males and 28 females aged (48.633.36) years old in average (youngest: 22; oldest: 69). The average disease course was (20.564.12) months (shortest: 6; longest: 35). The average education time was (17.254.12) years. Control group: Another 60 healthy subjects who received physical examinations in our hospital were selected. They did not have history

of autoimmune diseases symptoms such as joint pain and swelling other autoimmune diseases or hormone treatment. The observation group comprised 31 males and 29 females aged (49.003.75) years old in average (youngest: 23; oldest: 70). The average disease course was (20.724.00) months (shortest:

5; longest: 36). The average education time was (17.334.34) years. The gender age disease course and education time of the two groups did not differ significantly (Pgreater than 0.05). This study was approved by the Ethics Committee of our hospital and written consent was obtained from all enrolled subjects. Determination of B-lymphocytes: Blood (3 ml) was collected from the median cubital vein in the morning when the patients were in the fasting state and was left still for 2 h at room temperature after being treated by anticoagulants. Then the sample was centrifuged at 2500 rpm for 5-10 minutes and the supernatant was collected and stored at -20C. Serum BlyS level was measured by ELISA method according to the instructions of the kit provided by Sangon Biotech (Shanghai) Co. Ltd. CD19+CD25+ lymphocyte percentages were determined by flow cytometry (Epics-XL II Beckman Coulter USA) within 6 hour after separating the serum. Relevant antibodies were purchased from Beckman Coulter (USA).

Determination of trace elements: After separating the serum the levels of trace elements were determined by BH5100S atomic absorption spectrometer (Beijing Bohui Innovation Technology Co. Ltd.) with flame atomic absorption spectrophotometry. All reagents were prepared with deionized water and national standards. Reference ranges: Copper: 11.8-39.3 mol/L; zinc: 76.5-170.0 mol/L; selenium: 1.9-2.7 mol/L.

Statistical analysis: All data were analyzed by SPSS19.0. The categorical data were expressed as (xs) and compared by independent sample t-test. The numerical data were compared by Chi-square test. Linear correlation analysis was performed to calculate the Pearson's coefficient. Pless than 0.05 was considered statistically significant.

RESULTS

Expressions of serum BlyS: The serum BlyS levels of the observation group and the control group were (0.390.21) ng/ml and (0.130.04) ng/ml respectively which were significantly different (Pless than 0.05) (Table-I).

Table-I: Expressions of serum BlyS (ng/ml xs).

Group###Case number (n) BlyS expression level

Observation group 60 0.390.21

Control group###60 0.130.04

t16.521

P###less than 0.05

Table-II: Expressions of serum CD19+CD25+ cells (% xs).

###Group###Case number (n)###CD25+###CD19+###CD19+CD25+

###Observation group 60###8.812.01 10.242.11 0.510.21

###Control group###60###3.230.95 6.891.05 0.160.08

###t###13.008 7.24819.524

###P###less than 0.05###less than 0.05###less than 0.05

Table-III: Levels of trace elements (mol/L xs).

###Group###Case number (n)###Copper###Zinc###Selenium

###Observation group 60###14.363.22 86.5216.36 2.000.63

###Control group###60###26.864.12 141.6620.00 2.450.69

###t###9.6328.412 4.556

###P###less than 0.05###less than 0.05###less than 0.05

Expressions of serum CD19+CD25+ cells: The percentages of CD25+ CD19+ and CD19+CD25+ lymphocytes in the observation group significantly exceeded those in the control group (Pless than 0.05) (Table-II Fig. 1 and Fig. 2).

Levels of trace elements: The serum copper selenium and zinc levels of the observation group were significantly lower than those of the control group (Pless than 0.05) (Table-III).

Table-IV: Correlation between B-lymphocyte dysfunction and serum levels of copper selenium and zinc

IndexCopper Zinc###Selenium

r -0.541-0.370 -0.430

P less than 0.05 less than 0.05 less than 0.05

Correlation analysis: As evidenced by the Pearson's correlation analysis the BlyS level was correlated with the levels of copper selenium and zinc respectively (r=-0.541 -0.370 -0.430 Pless than 0.05) (Table-IV).

DISCUSSION

As a common frequently occurring disease RA endangers human health as an autoimmune disease that is manifested as synovitis and progressive destructions of cartilage and bone in clinical practice. Besides often giving rise to disability RA also adversely affects the physiology and psychology of patients.10 Although ubiquitous among all age groups RA is more prone to attacking older people. B-lymphocytes play a crucial role in the onset of RA because the involved synovial tissues contain abundant such cells that produce autoantibodies. Meanwhile B-lymphocytes are antigen-presenting cells for T cells.11 BlyS is involved in the proliferation and differentiation of B-lymphocytes. In case of over- expression it is closely related with autoimmune disease especially RA. In general BlyS enhances humoral immune response by inducing the proliferation differentiation and immunoglobulin secretion of B-lymphocytes.12 Moreover BlyS regulates the activation and response of T cells the over-expression of which may destroy the equilibria of cell production and autoimmune tolerance thus triggering many types of autoimmune diseases.13

In this study the BlyS levels of the two groups were significantly different suggesting that the expressions of B-lymphocytes in RA patients were evidently disordered.

For RA patients B-lymphocytes are the predominant infiltrating cells and the formation of synovial cell follicles is associated with the level of serum rheumatoid factor.14 As a 95 kD type I transmembrane glycoprotein CD19 is the restricted antigen of B-lymphocytes so the expression of CD19 corresponds to the level of B-lymphocyte.15 Moreover CD28 molecule is the surface activation marker for B-lymphocytes by being related with their development and maturity. CD19+CD25+ lymphocytes are the intermediates of B-lymphocyte's differentiation into plasmocyte that can produce antibodies. In this study the percentages of CD25+ CD19+ and CD19+CD25+ lymphocytes in the observation group significantly Table-IV: Correlation between B-lymphocyte dysfunction and serum levels of copper selenium and zinc.

exceeded those in the control group indicating that RA patients had abnormally proliferated cell subsets. BlyS may promote the transformation of B-lymphocytes into plasmocytes and boost humoral immune response by increasing the percentage of CD19+CD25+ lymphocytes.

Of the trace elements in human body copper is the main component of proteins and enzymes energizes biochemical processes contributes to the interaction between collagen and elastin and affects functions of the immune system.1617 As the component and activator of some enzymes zinc is conducive to the growth development and tissue regeneration of human body is involved in several immune functions and may protect against the development of RA.17-19 As the source of life selenium can resist oxidation reinforce the immune system facilitate human development and growth prevent infectious diseases and mitigate inflammation induced by autoimmune diseases such as RA and systemic lupus erythematosus.171920

In this study the serum levels of copper selenium and zinc in the observation group were significantly lower than those in the control group. Meanwhile the BlyS level was correlated with the levels of copper selenium and zinc respectively (r = -0.541 -0.370 -0.430 Pless than 0.05). Hence trace elements should be supplemented according to specific symptoms in clinical practice.

In summary RA may be induced by BlyS- mediated B-lymphocyte dysplasia and dysfunction which is accompanied by reduced levels of copper selenium and zinc. Furthermore the results suggest that BlyS and trace elements may participate in the onset of RA.

Conflicts of interest: All the coauthors declare that they have no conflicts of interest.

REFERENCES

1. Liang D Zeng Q Xu Z Zhang H Gui L Xu C et al. BAFF activates Erk1/2 promoting cell proliferation and survival by Ca(2+)- CaMKII-dependent inhibition of PP2A in normal and neoplastic B-lymphoid cells. Biochem Pharmacol. 2014;87(2):332-343. doi: 10.1016/j.bcp.2013.11.006.

2. Tardivel A Tinel A Lens S Steiner QG Sauberli E Wilson A et al. The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF. Eur Immunol. 2004;34(2):509-518. doi: 10.1002/ eji.200324692

3. Luu VP Hevezi P Vences-Catalan F Maravillas-Montero JL White CA Casali P et al. TSPAN33 is a novel marker of activated and malignant B cells. Clin Immunol. 2013;149(3):388-399. doi: 10.1016/j.clim.2013.08.005.

4. IndrevAr RL Holm KL Aukrust P Osnes LT Naderi EH Fevang B et al. Retinoic acid improves defective TLR9/RP105-induced immune responses in common variable immunodeficiency- derived B cells. J Immunol. 2013;191(7):3624-33. doi: 10.4049/ jimmunol.1300213. 5. Stohl W Metyas S Tan SM Cheema GS Oamar B Xu D et al. B lymphocyte stimulator over expression in patients with systemic lupus erythematos US longitudinal observations. Arthritis Rheum. 2003;48(12):3475-3486. doi: 10.1002/art.11354.

6. Zhang C Myers JL. Crystal-storing histiocytosis complicating primary pulmonary marginal zone lymphoma of mucosa- associated lymphoid tissue. Arch Pathol Lab Med. 2013;137(9):1199- 1204. doi: 10.5858/arpa.2013-0252-CR.

7. Wang J Shan Y Jiang Z Feng J Li C Ma L et al. High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis. Clin Exp Immunol. 2013;174(2):212-220. doi: 10.1111/cei.12162.

8. Tan SM Xu D RoschkeV Perry JW Arkfeld DG Ehresmann GR et al. Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003;48(4):982-992. doi: 10.1002/art.10860.

9. Lucchesi D Bombardieri M. The role of viruses in autoreactive B cell activation within tertiary lymphoid structures in autoimmune diseases. J Leukoc Biol. 2013;94(6):1191-1199. doi: 10.1189/ jlb.0413240.

10. Goules JD Goules AV Tzioufas AG. Fine specificity of anti- citrullinated peptide antibodies discloses a heterogeneous antibody population in rheumatoid arthritis. Clin Exp Immunol. 2013;174(1):10-17. doi: 10.1111/cei.12145.

11. van Baarsen LG de Hair MJ Ramwadhdoebe TH Zijlstra IJ Maas M Gerlag DM et al. The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis. Ann Rheum Dis. 2013;72(8):1420-1424. doi: 10.1136/annrheumdis-2012-202990.

12. Kerkman PF Rombouts Y van der Voort EI Trouw LA Huizinga TW Toes RE et al. Circulating plasmablasts/plasmacells as a source of anticitrullinated protein antibodies in patients with rheumatoid arthritis. Ann Rheum Dis. 2013;72(7):1259-1263. doi: 10.1136/annrheumdis-2012-202893.

13. Endale M Lee WM Kwak YS Kim NM Kim BK Kim SH et al. Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthritis. Int Immunopharmacol. 2013;16(2):232-242. doi: 10.1016/j.intimp.2013.04.012.

14. Stohl W Merrill JT McKay JD Lisse JR Zhong ZJ Freimuth WW et al. Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II randomized double-blind placebo-controlled dose-ranging Study. J Rheumatol. 2013;40(5):579-589. doi: 10.3899/ jrheum.120886.

15. Pera J Korostynski M Golda S Piechota M Dzbek J Krzyszkowski T et al. Gene expression profiling of blood in ruptured intracranial aneurysms: in search of biomarkers. J Cereb Blood Flow Metab. 2013;33(7):1025-1031. doi: 10.1038/jcbfm.2013.37.

16. Choy EH Kavanaugh AF Jones SA. The problem of choice: current biologic agents and future prospects in RA. Nat Rev Rheumatol. 2013;9(3):154-163. doi: 10.1038/nrrheum.2013.8.

17. Onal S Naziroglu M Colak M Bulut V Flores-Arce MF. Effects of different medical treatments on serum copper selenium and zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res. 2011;142(3):447-455. doi: 10.1007/s12011-010-8826-7.

18. Afridi HI Kazi TG Kazi N Talpur FN Shah F Naeemullah et al. Evaluation of status of arsenic cadmium lead and zinc levels in biological samples of normal and arthritis patients of age groups (46 - 60) and (61 - 75) years. Clin Lab. 2013;59(1-2):143-153. doi: 10.7754/Clin.Lab.2012.120126.

19. Selmi C Tsuneyama K. Nutrition geoepidemiology and autoimmunity. Autoimmun Rev. 2010;9(5):A267-270. doi: 10.1016/j.autrev.2009.12.001.

20. Arthur JR McKenzie RC Beckett GJ. Selenium in the immune system. J Nutr. 2003;133(5 Suppl 1):1457S-1459S.
COPYRIGHT 2014 Asianet-Pakistan
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2014 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Publication:Pakistan Journal of Medical Sciences
Date:Oct 31, 2014
Words:2608
Previous Article:Tissue polypeptide antigen and interleukin-6: Are their serum levels a predictor for response to chemotherapy in breast cancer.
Next Article:The effect of intravenous dexamethasone in the treatment of septic arthritis.
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters