Cause-effect relations between 55 kD soluble TNF receptor concentrations and specific and unspecific symptoms in a patient with mild SLE disease activity: an exploratory time series analysis study

BMC Research Notes

Dietmar Fuchs²  Mirjam Schnapka-Köpf³  Norbert Sepp⁴  Paul König⁶  Francisco M. Ocaña-Peinado¹  Julia Haberkorn⁵  Christian Schubert⁵ 

[1] Department of Statistics and Operations Research, University of Granada, Granada, Spain;Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria;Central Institute of Medical and Chemical Laboratory Diagnostics, University Clinics, Innsbruck, Austria;Clinical Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria;Clinical Department of Medical Psychology, Innsbruck Medical University, Schöpfstraße 23a, Innsbruck, 6020, Austria;Clinical Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria

关键词: Single case study;    Cross-correlation;    ARIMA modeling;    Time series analysis;    Facial rash;    Oral ulcer;    Proteinuria;    Lupus;    sTNF-R55;   

Others  :  1230096
DOI  :  10.1186/s13104-015-1398-z

 received in 2013-11-03, accepted in 2015-08-31,  发布年份 2015

【 摘 要 】

Background

This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity.

Methods

The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05).

Results

Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36–48 h (r = −0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24–36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36–48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36–48 h (r = −0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36–48 h (r = −0.223) and followed increased body temperature after 36–48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels.

Conclusions

This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These findings require replication before firm conclusions can be drawn.

【 授权许可】

   
2015 Schubert et al.

【 图 表 】

Fig.1.

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【 参考文献 】

• [1]Lee HM, Sugino H, Nishimoto N. Cytokine networks in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:676284. doi:10.1155/2010/676284.
• [2]Jacob N, Stohl W: Cytokine disturbances in systemic lupus erythematosus. Arthritis Res Ther 2011, 13:228. BioMed Central Full Text
• [3]MacEwan DJ: TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 2002, 14:477-492.
• [4]Davas EM, Tsirogianni A, Kappou I, Karamitsos D, Economidou I, Dantis PC: Serum IL-6, TNFalpha, p55 srTNFalpha, p75srTNFalpha, srIL-2alpha levels and disease activity in systemic lupus erythematosus. Clin Rheumatol 1999, 18:17-22.
• [5]Wais T, Fierz W, Stoll T, Villiger PM: Subclinical disease activity in systemic lupus erythematosus: immunoinflammatory markers do not normalize in clinical remission. J Rheumatol 2003, 30:2133-2139.
• [6]Van Hauwermeiren F, Vandenbroucke RE, Libert C: Treatment of TNF mediated diseases by selective inhibition of soluble TNF or TNFR1. Cytokine Growth Factor Rev 2011, 22:311-319.
• [7]Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF: Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci USA 1992, 89:4845-4849.
• [8]Schubert C, Geser W, Noisternig B, Fuchs D, Welzenbach N, König P, Schüßler G, Ocaña-Peinado FM, Lampe A: Stress system dynamics during “life as it is lived”: an integrative single-case study on a healthy woman. PLoS One 2012, 7:e29415.
• [9]American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria: The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials: measures of overall disease activity Arthritis Rheum 2004, 50:3418-3426.
• [10]Trull TJ, Ebner-Priemer UW: Using experience sampling methods/ecological momentary assessment (ESM/EMA) in clinical assessment and clinical research: introduction to the special section. Psychol Assess 2009, 21:457-462.
• [11]Schubert C, Lampe A, Geser W, Noisternig B, Fuchs D, König P, Chamson E, Schüssler G: Daily psychosocial stressors and cyclic response patterns in urine cortisol and neopterin in a patient with systemic lupus erythematosus. Psychoneuroendocrinology 2003, 28:459-473.
• [12]Schubert C, Noisternig B, Fuchs D, König P, Chamson E, Mittnik S, Schüßler G, Geser W: Multifaceted effects of positive incidents on urine cortisol and urine neopterin dynamics in a patient with systemic lupus erythematosus. Stress Health 2006, 22:215-227.
• [13]Schubert C, Lampe A, Geser W, Merk M, Jenny M, Fuchs D: Temporal association between daily alcohol consumption, emotional states and urinary neopterin levels in a patient with systemic lupus erythematosus. Pteridines 2009, 20:62-71.
• [14]Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M: The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004, 15:241-250.
• [15]Fuchs D, Weiss G, Reibnegger G, Wachter H: The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 1992, 29:307-341.
• [16]Iwata J, Nishikaze O: New micro-turbidimetric method for determination of protein in cerebrospinal fluid and urine. Clin Chem 1979, 25:1317-1319.
• [17]IBM Corp. IBM SPSS Statistics for Windows. Version 20.0. NY: Armonk; 2011.
• [18]Box GEP, Jenkins GM: Time-series analysis: forecasting and control. Holden-Day, San Francisco; 1976.
• [19]Lange T, Dimitrov S, Born J: Effects of sleep and circadian rhythm on the human immune system. Ann NY Acad Sci 2010, 1193:48-59.
• [20]Schubert C, Cornélissen G, Halberg F. About half-weekly (circasemiseptan) rhythm in urinary neopterin of healthy woman: methodologic model. In: Kenner T, Cornélissen G, Siegelová J Dobsák P, editors. Noninvasive methods in cardiology. Brno: Faculty of Medicine, Masaryk University; 2013. p. 96–101.
• [21]Maschke C, Harder J, Cornélissen G, Hecht K, Otsuka K, Halberg F: Chronoecoepidemiology of “strain”: infradian chronomics of urinary cortisol and catecholamines during nightly exposure to noise. Biomed Pharmacother 2003, 57(Suppl 1):126s-135s.
• [22]Ulmer W, Cornélissen G, Halberg F: Interaction among (quantum mechanical) resonance-coupled electromagnetic circuits relevant to a natural week. WHJ 2012, 4:35-70.
• [23]Olszyna DP, Prins JM, Buis B, van Deventer SJ, Speelman P, van der Poll T: Levels of inhibitors of tumor necrosis factor alpha and interleukin 1beta in urine and sera of patients with urosepsis. Infect Immun 1998, 66:3527-3534.
• [24]Waller KV, Ward KM, Mahan JD, Wismatt DK: Current concepts in proteinuria. Clin Chem 1989, 35:755-765.
• [25]Koolhaas JM, Meerlo P, De Boer SF, Strubbe JH, Bohus B: The temporal dynamics of the stress response. Neurosci Biobehav Rev 1997, 21:775-782.
• [26]Von Storch J-S: Signatures of air–sea interactions in a coupled atmosphere-ocean GCM. J Clim 2000, 13:3361-3379.
• [27]Bemelmans MH, Gouma DJ, Buurman WA: Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J Immunol 1993, 150:2007-2017.
• [28]Lütkepohl H: New introduction to multiple time series analysis. Springer, Berlin; 2005.
• [29]Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9:46-56.