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- Springer Journals
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- Copyright © The Author(s) 2023
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- 10.1186/s42358-023-00291-6
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Abstract
Objectives BDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE. Methods We searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle–Ottawa scale was used to assess the quality of the included publi- cations, and statistical analyses were carried out using R 4.0.4. Results The final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [ − 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [ − 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R were 26.89%, 16.53%, 18.8%, and 49.96%, respectively). Conclusion In conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies. Keywords Brain-derived neurotrophic factor, BDNF, Systemic lupus erythematous, SLE, Lupus, Neuropsychiatry lupus *Correspondence: School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Nima Rezaei Neuropsychiatry Program, Department of Psychiatry and Behavioral rezaei_nima@yahoo.com Sciences, McGovern Medical School, The University of Texas Health School of Medicine, Children’s Medical Center Hospital, Tehran Science Center at Houston, Houston, TX, USA University of Medical Sciences ( TUMS), Dr. Qarib St., Keshavarz Blvd, Department of Immunology, School of Medicine, Tehran University Tehran 14194, Iran of Medical Sciences, Tehran, Iran Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. Shobeiri et al. Advances in Rheumatology (2023) 63:8 Page 2 of 12 “Brain-Derived Neurotrophic-Factor”, “BDNF”, and using Introduction a combination of subject words and free words. No lan- Systemic lupus erythematosus (SLE) is a chronic autoim- guage, publication date, or publication status restric- mune disease that affects several organs in the body and tions (e.g., online first or published) were applied. To is more common among females [1]. Genetically predis- identify additional studies, we further checked refer- posed individuals seem to develop loss of T-cell tolerance ence lists and contacted the corresponding authors of to self-antigens [2], resulting in increased production the papers included in the current systematic review and of autoantibodies and an imbalance between Th17 and meta-analysis. regulatory T-cells [3, 4]. The deposition of immune com - plexes in various organs including kidneys, lungs, and Eligibility criteria central nervous system (CNS) is partly responsible for Only studies that investigated the circulating blood lev- the disease symptoms [5, 6]. els of BDNF in SLE patients were eligible to be included. The diagnosis of SLE is based on international classifi - No language or time restrictions were applied. The main cation criteria which include both clinical and laboratory outcome included the BDNF levels in SLE patients and findings [7]. Clinical manifestations of the disease can healthy controls (HCs). range from mild symptoms, like arthralgia and cutane- Studies that reported only the levels of BDNF for par- ous lupus, to severe and life-threatening manifestations, ticipants with SLE without comparing to an HC group including lupus nephritis [8]. Neuropsychiatric features were also excluded. Review articles, books, book chap- are one of the most common manifestations among SLE ters, studies on animal subjects, studies assessing tissue patients [9]. It can present a wide spectrum of symptoms, expression of BDNF, in vitro studies or studies on cell from depression and seizures to stroke [10]. Of note, cultures, and studies on genetic polymorphisms of BDNF the CNS is involved in about 75% of SLE patients, and but not its levels were also excluded. the pathophysiology of neuropsychiatric SLE (NPSLE) remains to be understood [11]. Data extraction and quality assessment Recent studies have highlighted the role of neuro- The data were pre-extracted from the documents. Two trophins, especially BDNF, in the pathophysiology of authors performed two-stage screening (title/abstract immune-based diseases. Traditionally, BDNF has been and full-text), data extraction, and risk of bias assess- implicated in neuronal growth and survival, i.e., neu- ment independently to select the eligible studies. A third roprotective effects [12, 13]. BDNF can be produced investigator was consulted in case of discrepancies in the by lymphocytes, macrophages, endothelial cells, [14], data extraction and quality assessment process. The fol - enhancing the proliferation and survival of the lympho- lowing items were extracted from the included studies: cytes by affecting the cell membrane through autocrine Author, Year, Country, Study Design, BDNF Measure- or paracrine signaling [15, 16]. To date, several systematic ment Protocol Source (Serum, Plasma), Sample size (SLE reviews and meta-analysis attempted to shed light on the and HCs), Diagnostic Criteria, Age, Female/Male ratio, role BDNF in various disorders, including multiple scle- BDNF levels, Investigated Markers, and the Main Signifi - rosis, eating disorders, and sleep apnea [17–20]. cant Findings. Taken together, since there could be a relationship Newcastle–Ottawa scale (NOS) was used to evaluate between BDNF and SLE disease neuropsychiatric symp- the quality of the included studies [22]. Using this scale, toms and severity; therefore, we conducted a meta-anal- studies can be rated 0–9 stars based on the selection of ysis of the studies investigating blood BDNF levels in SLE their samples, the comparability of cases and controls, patients compared to controls. and the assessment of their outcomes. Studies with a star rating of 7–9 were considered of the best quality, a rat- Materials and methods ing of 4–6 stars, a moderate quality, and a rating of fewer The current systematic review and meta-analysis fol - than four had the lowest quality. lowed the methods of the Cochrane Handbook of Sys- tematic Reviews and the guidelines from the Preferred Statistical analysis Reporting Items for Systematic Reviews and Meta-Analy- The standardized mean difference (SMD) was used to ses (PRISMA 2020) [21]. measure the effect. Also, random effects were utilized as the analysis model. Statistical methods suggested by Luo Search strategy et al. [23] and Wan et al. [24] were used when the values PubMed, EMBASE, and Cochrane Library were searched reported in the manuscript were expressed as a median till April 2022 using the retrieval words “Systemic lupus and interquartile range (IQR) or median and range, and erythematosus”, “lupus”, “SLE”, “Neuropsychiatric lupus”, Shobeir i et al. Advances in Rheumatology (2023) 63:8 Page 3 of 12 we could not get the mean and SD from the authors. (version 2.4-0), “dmetar” (version 0.0-9), and “tidyverse” Q statistic tests and the I index were used to detect (version 1.3.0). A P value of < 0.05 was considered statisti- heterogeneity. According to the Cochrane criteria, an cally significant. I < 40% indicates that discrepancy across investigations is not significant. We intended to utilize the fixed effects Results approach in this scenario. We employed the random Study selection effects approach as the analytical model if the I estima- The study selection process is shown in Fig. 1. The search tions changed by more than 40%. We ran a sensitivity database returned a total of 208 entries. After removing analysis to identify influential cases for meta-analyses duplications, 168 articles were retrieved for preliminary with considerable heterogeneity, containing ten or more screening. The full text of 17 publications was read by paper to further investigate the sources of heterogeneity. two independent reviewers who assessed the final eli - We removed one research each time and recalculated the gibility under the supervision of a senior team member. effect size (Leave-One-Out Analyses). Four studies were excluded since these manuscripts did We assessed publication bias through funnel plot and not encompass healthy control groups. We omitted nine Egger’s test. The degree of asymmetry in the funnel plot articles due to the reasons mentioned in Fig. 1. At the and Egger’s test [25] identify publication bias. In particu- end, we selected eight papers including 660 SLE patients lar, funnel plots are frequently used to visually identify and 323 HCs. publication bias. The Egger’s test, on the other hand, is an objective statistic that helps individuals to validate visual Characteristics of the included studies cues provided by funnel plots. According to Table 1, eight studies published from All computations and visualizations were carried out 2009 to 2021 provided original data on BDNF blood using R version 4.0.4 (R Core Team [2020]. R: A language levels in SLE patients and HCs [26–33]. SLE patients and environment for statistical computing. R Foundation were selected based on the ACR criteria. Two studies for Statistical Computing, Vienna, Austria). We used the only compared BDNF levels in SLE patients (n = 59) following packages: “meta” (version 4.17-0), “metafor” to HCs (n = 64) [27, 29]. Meanwhile, six studies gave Fig. 1 Flow diagram summarizing the selection of eligible studies based on the PRISMA guidelines Shobeiri et al. Advances in Rheumatology (2023) 63:8 Page 4 of 12 Table 1 Baseline characteristics of included studies Study ID Patients Controls Results References Country Study BDNF Source No. (type Diagnostic Age Female/ BDNF levels No Age Female/ BDNF levels Investigated Main design measurement (serum, of SLE) criteria (mean ± SD), male (mean ± SD), pg/ml (Type of (mean ± SD), male (mean ± SD), pg/ml markers significant protocol plasma) years control) years findings Ikenouchi- Japan Cross- Emax Immuno- Serum 54 ACR 40.10 ± 1.98 49/5 15,984.4 ± 11,820.828 40.4 ± 2.08 25/3 11,440 ± 690 BDNF Serum BDNF Sugita et al. sectionalassey levels were [26] Kit (Promega, significantly Madison, WI, increased in USA) the NP group Fauchais et al. France Cross- ELISA Kits Serum 26 ACR 44 ± 12 24/2 598.9 ± 129.8 26 24/2 326.10 ± 60.50BDNF They have [27] sectional NGF demon- NT3 strated that CH50 both NGF Anti-nuclear and BDNF Ab/nDNA serum levels are higher in SLE patients than healthy controls Tamashiro Brazil Cross- ELISA (R&D Plasma 131 ACR 32.78 ± 12.36 120/11 3870.8066 ± 4793.357524 33 ± 9 15/9 2205.4269 ± 2938.6665BDNF BDNF et al. [28] sectionalSystems, Min- ANA levels were + Lon- neapolis, MN, aPL increased gitudinal USA) Anti-ribosomal in inactive stage P protein NPSLE when Anti-dsDNA compared C3, C4 with active SLE and controls Zheng et al. China Cross- ELISA (R&D Serum 208 SDI score, 55.70 ± 10.45 190/18 33,654.3 ± 9032.9100 55.70 ± 10.53 0/0 14,694.4 ± 4438 BDNF The serum [30] sectionalSystems, Min- SLEDAI-2 K EGFR BDNF neapolis, MN, score, Anti-dsDNA levels were USA) VAS score ANA significantly Anti-sm anti- higher in SLE body patients as CRP compared C3 to normal C4 controls The serum BDNF levels were signifi- cantly lower in depression patients at the time of admission as compared with patients without depression Shobeir i et al. Advances in Rheumatology (2023) 63:8 Page 5 of 12 Table 1 (continued) Study ID Patients Controls Results References Country Study BDNF Source No. (type Diagnostic Age Female/ BDNF levels No Age Female/ BDNF levels Investigated Main design measurement (serum, of SLE) criteria (mean ± SD), male (mean ± SD), pg/ml (Type of (mean ± SD), male (mean ± SD), pg/ml markers significant protocol plasma) years control) years findings Kalinowska- Poland Cohort ELISA Kits (Multi- Serum 38 ACR 40 ± 12 36/2 424.8199 ± 676.23939 1766.9266 ± 1161.4063BDNF BDNF Łyszczarz Neurotrophin (BDNF was BDNF was NGF levels were et al. [29] Rapid Screening detected detected NT3 reduced ELISA Kit) in 33 in 38 NT4/5 in NPSLE patients) patients) compared to the healthy population Noris-GarCia Cuba Cross- ELISA Kit (BDNF Serum 47 ACR-97 47 ± 11 45/2 4210 ± 1783.4 20 47 ± 13 16/4 4494 ± 1739.3 BDNF BDNF et al. [32] sectionalELISA, Promega, S100B levels were Charbonnieres, ANA significantly France) Anti-dsDNA decreased Anti-cardiolipin in active antibodies, SLE, when Anti-neutrophil compared cytoplasmic with inactive antibodies SLE Tian et al. [33] China Cross- ELISA (DBNT00, Serum 50 ACR 31.9 ± 14.9 45/5 14,742.5 ± 7620.930 33,116.5 ± 7146.5BDNF Serum BDNF sectionalR&D Systems, TrkB expression levels in SLE Minneapolis, patient were USA) decreased when com- pared to the controls BDNF level was increased in inactive SLE group compared to the active SLE group Alessi et al. Brazil Cross- ELISA (Norcross, Serum 111 SLICC 38.28 ± 10.64 102/9 788,651.4 ± 458,815.557 41.6 ± 48/9 1,345,500 ± 438,400 BDNF Serum BDNF [31] sectionalGA, USA) 11.1 Anti-sm anti- levels were bodies, ANA, lower in SLE Anti-LA/SSB and NPSLE Anti-Ro/SSA patients Anti-P than control Anti-DNA group Anti-RNP ELISA Enzyme-Linked Immunosorbent Assay, BDNF Brain-derived neurotrophic factor, NGF Nerve growth factor, IGFBP1 Insulin-like growth factor-binding protein 1, SLE Systemic Lupus Erythematosus, NPSLE Neuropsychiatry SLE, SLEDAI-2 K SLE disease activity index 2000, SDI Systemic lupus international collaborating/American College of Rheumatology damage index for SLE, SLICC Systemic Lupus International Collaborating Clinics criteria Shobeiri et al. Advances in Rheumatology (2023) 63:8 Page 6 of 12 Table 2 Newcastle–Ottawa Scale (NOS) risk of bias assessment of the included studies References Selection Comparability (0–2) Exposure/outcome (0–3) Total score (0–10) (0–5) Ikenouchi-Sugita et al. [26] 3 1 3 7 Fauchais et al. [27] 4 1 3 8 Tamashiro et al. [28] 4 2 3 9 Zheng et al. [30] 3 1 3 7 Kalinowska-Łyszczarz et al. [29] 4 1 3 8 Noris-GarCia et al. [32] 4 1 2 7 Tian et al. [33] 4 2 3 9 Alessi et al. [31] 3 2 3 8 The methodological quality of studies additional information about BDNF levels in differ- The results of quality assessments of the included ent groups of SLE patients. The mean ± SD age range studies using the Newcastle Ottawa scale (NOS) for was from 31.9 ± 14.9 to 55.7 ± 10.45 years among SLE cross-sectional studies are depicted in Table 2. patients and from 33 ± 9 to 55.7 ± 10.53 years among HCs. The majority of the participants were females. Comparison of BDNF levels in SLE patients versus healthy All but one study [26] used enzyme-linked immuno- controls (HCs) sorbent assay (ELISA) to measure BDNF levels as an Meta-analysis results of the eight studies did not reveal analytical procedure. Moreover, all studies assessed statistically significant difference in blood BDNF serum BDNF levels, except the study by Tamashiro et al. [28] which examined plasma levels of BDNF. Fig. 2 A Forest plot of meta-analysis of BDNF levels in SLE patients compared to controls., B Forest plot of meta-analysis of BDNF levels in SLE patients removing outliers Shobeir i et al. Advances in Rheumatology (2023) 63:8 Page 7 of 12 Publication bias concentrations in SLE patients compared to HCs (SMD The Eggers’ test did not indicate the presence of substan - 0.0872, 95% CI [ − 1.1538; 1.3282], P value = 0.8904, tial funnel plot asymmetry (P value = 0.47). Also, the fun- I = 98.3%, test of heterogeneity: Q = 418.20, nel plot was symmetric (Fig. 3). P value < 0.0001, Fig. 2A). The heterogeneity between studies was statistically sig - Outliers’ identification and sensitivity analysis nificant (P value < 0.0001), with a variance of τ = 3.1387 By means of the ‘find.outliers’ command in R software, [1.2670; 13.1168] and an I value of 98.3% [97.7%; 98.8%]. three studies [27, 30, 33] were regarded as outliers; there- The prediction CI ranged from − 4.5164 to 4.6908, sug- fore, the remaining five studies were re-analyzed, and the gesting that negative intervention effects in future trials following results were acquired: SMD − 0.3868 (95% CI cannot be ruled out. Fig. 3 A The funnel plot showing no evidence of publication bias, statistically supported by Egger’s regression test. B Counter-enhanced funnel plot Shobeiri et al. Advances in Rheumatology (2023) 63:8 Page 8 of 12 Meta‑regression [ − 1.1714; 0.3978], P value = 0.3339, I = 93.4%, test of We employed meta-regression analysis to identify the heterogeneity: Q = 61.01, P value < 0.0001, Fig. 2B). These origins of study heterogeneity and the impact of modi- results corroborate that BDNF levels were not statisti- fiers. Univariate meta-regression analysis revealed cally different between SLE patients and HCs. that sample size, number of males, NOS score, and The impact of each study on the total estimate was evalu - mean age of the SLE participants account for the exist- ated by systematically eliminating studies and comparing the ing heterogeneity (R were 26.89%, 16.53%, 18.8%, and pooled estimate from the remaining seven investigations. 49.96%, respectively). Also, according to meta-regres- SLE patients exhibited higher peripheral BDNF levels than sion results, the mean age of the SLE participants had a controls, meaning that eliminating any research work would statistically positive correlation to BDNF levels. Table 3 have minimal influence on the overall findings (Fig. 4 ). Fig. 4 Results of Sensitivity analysis (leave-one-out analysis) of the meta-analysis A Sorted by I ; B Sorted by Eec ff t Sizes Shobeir i et al. Advances in Rheumatology (2023) 63:8 Page 9 of 12 Table 3 Meta-regression of BDNF levels in SLE patients and healthy controls Moderator No. of No. of subjects Meta‑regression R Analog comparisons (proportion IHD HC Slope 95% CI P value of variance explained) (%) Sample size 8 658 323 0.0099 − 0.0081; 0.0278 0.2818 26.89 Age (mean, 8 658 323 0.1556 0.0339; 0.2772 0.0122 49.96 years) NOS score 8 658 323 − 0.9676 − 2.4017; 0.4665 0.1860 18.80 Sex (male, %) 7 625 285 0.0836 − 0.1464; 0.3135 0.4762 16.53 P value < 0.05 is shown in Bold Fig. 5 Bubble plot of meta-regression A Mean Age; B NOS Score; C Sample Size; D Sex (Male) summarizes the results of meta-regression analysis, and disorders, and cognitive dysfunction [35]. There is still the bubble plots are shown in Fig. 5. no single sensitive and specific test for diagnosing SLE- associated neurologic/neuropsychiatric manifestations; Discussion therefore, the assessment of SLE patients for CNS-related To the best of our knowledge, this is the first meta-anal - manifestations is based on the consideration of clinical ysis of BDNF blood levels in SLE patients. Pooling the findings, brain imaging, and immunoserologic mark - results of the eight studies did not show statistically sig- ers [35]. Several studies have suggested alterations in the nificant differences between SLE patients and HCs. serum BDNF levels in SLE patients [31, 36, 37]. BDNF SLE is a systemic autoimmune disease manifesting with is one of the most studied neurotrophic factors in the various symptoms ranging from mild mucocutaneous CNS, which serves as an autocrine and paracrine factor symptoms to systemic and multiorgan involvement [34]. on pre-synaptic and post-synaptic sites [38]. BDNF is SLE can be associated with a series of neurological and known to be a key molecule in regulating neurogenesis, neuropsychiatric manifestations, including headaches, synaptic plasticity, and, thus, learning and memory func- seizures, cerebrovascular events, psychosis, movement tions [39]. Memory impairment is one of the neurological Shobeiri et al. Advances in Rheumatology (2023) 63:8 Page 10 of 12 symptoms associated with SLE [40]; however, the medi- suggested in Tian et al.’s study [33]. In addition, they ating role of BDNF level alterations in the pathophysiol- observed lower levels of serum BDNF in SLE patients ogy of SLE-related memory and cognitive impairment is without lupus nephritis [33]. Consistently, Noris-García unclear. Alessi et al. observed that serum BDNF levels et al. [32] found that BDNF levels were significantly lower were lower among SLE and NPSLE cases compared with among patients with active SLE, compared with individu- controls; but were not associated with NPSLE-related als inactive SLE, however, not when compared with HCs. cognitive dysfunction [31]. On the other hand, serum On the other hand, Ikenouchi et al. found no correlations BDNF levels seem to be lower in SLE subjects exhibit- between SLEDAI scores and serum BDNF levels in SLE ing depressive symptoms, indicating the role of BDNF patients [26]. This is in line with the findings of Fauchais in maintaining mental health in SLE patients [30]. In et al. [27]; accordingly, BDNF serum levels was not asso- line with the previously mentioned findings, Ikenouchi- ciated with initial SLEDAI scores. Taken together, there is Sugita et al. [26] observed that patients with NPSLE were inconsistency between the results of the studies regard- found to have lower levels of BDNF than controls, and ing the relationship of BDNF with SLE clinical course this reduction was related to the progression and sever- which may arise from different sample sizes, taking medi - ity of psychiatric symptoms. Of note, serum BDNF levels cations interfering with BDNF serum levels, or other pos- have been reported to be decreased in major depression sible reasons. Hence, further concise evaluations should and to improve with antidepressants treatment [41, 42]. be conducted to shed light on the variations of BDNF lev- Interestingly, consistent with the findings of human stud - els in different clinical stages of SLE, which may enable ies, preclinical studies have shown that different types of clinicians to use BDNF or other neurotrophins as a bio- stress suppress the expression of BDNF in limbic regions marker of SLE treatment response in the future. [43]. Our study has limitations. First, most of the included Tamashiro et al. [28] conducted a study with 131 SLE studies had relatively small sample sizes; hence the find - patients and 24 HCs. Plasma BDNF levels were elevated ings cannot be generalized to the SLE total population. in asymptomatic NPSLE compared with both active SLE Second, the SLE and control groups were not matched and HCs. Moreover, plasma BDNF levels increased as for age and sex in some of the studies. the neuropsychiatric symptoms improved, which cor- roborates the hypothesis that BDNF may lead to symp- Conclusion toms’ alleviations [28]. Conversely, a case report study In sum, according to our meta-analysis, SLE was not described that plasma levels of BDNF increased in paral- associated with the blood levels of BDNF. Future stud- lel with the severity of psychotic symptoms in a patient ies with larger sample sizes are required to determine the with CNS lupus [37]. While this latter finding challenges role of BDNF in SLE taking into account different sub - the view that lower levels of serum BDNF are associated groups of patients (e.g., NPSLE vs. non-NPSLE; active vs. with psychiatric symptoms, it provides a more nuanced controlled SLE) and its potential relation with established scenario in SLE. The higher levels of BDNF in the con - disease biomarkers. text of SLE-related psychosis probably indicates immune system hyperactivation and, therefore, greater produc- Abbreviations tion of BDNF [37]. Indeed, it has been suggested that ACLE Acute cutaneous lupus erythematosus activated B and T lymphocytes induce the production of BDNF Brain-derived neurotrophic factor CI Confidence interval BDNF, highlighting the regulating role of inflammation in CNS Central nervous system BDNF levels [44, 45]. Moreover, it should be noted that DLE Discoid lupus erythematosus blood BDNF levels do not always reflect its brain concen -HCs Healthy controls IQR Interquartile range trations [46, 47]. For example, in depression, BNDF lev- NOS Newcastle–Ottawa scale els are increased in specific brain regions, however, they NPSLE Neuropsychiatric systemic lupus erythematosus decrease in the blood [46], which points to the possible SCLE Subacute cutaneous lupus erythematosus SD Standard deviation discordance between the blood and brain concentrations SLE Systemic lupus erythematosus of BDNF. SLEDAI Systemic lupus erythematosus disease activity index The correlation between serum BDNF levels and the SMD Standardized mean difference severity of SLE course seems complicated. Tamashiro Acknowledgements et al. noticed that the level of plasma BDNF levels were This study was supported by a Grant from Tehran University of Medical Sci- higher in patients with inactive disease; indeed, SLE ences (Grant number: 64944). disease activity index (SLEDAI) scores, which show Author contributions the systemic activity in SLE, were negatively correlated PS: drafting of the manuscript/study conception and design/data acquisi- with plasma BDNF levels [28]. The same findings were tion, analysis and data interpretation, SM: drafting of the manuscript/data Shobeir i et al. Advances in Rheumatology (2023) 63:8 Page 11 of 12 acquisition, MA, AH: drafting of the manuscript, ALT: critical revision, NR: study acetate-reactive T-helper cell lines: Implications for multiple sclerosis conception and design/critical revision. All authors read and approved the therapy. J Neurol Sci. 2005;233(1–2):109–12. final manuscript. 15. D’Onofrio M, De Grazia U, Morrone S, Cuomo L, Spinsanti P, Frati L, et al. Expression of neurotrophin receptors in normal and malignant B lympho- Funding cytes. Eur Cytokine Netw. 2000;11(2):283–92. Not applicable. 16. Skaper SD. The biology of neurotrophins, signalling pathways, and func- tional peptide mimetics of neurotrophins and their receptors. CNS Neurol Availability of data and materials Disord Drug Targets. 2008;7(1):46–62. All recorded data from data extraction process of this study is available upon 17. Karimi N, Ashourizadeh H, Pasha BA, Haghshomar M, Jouzdani T, Shobeiri request to the corresponding author. P, Teixeira AL, Rezaei N. Blood levels of brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis (MS): a systematic review and meta-analysis. Mult Scler Relat Disord. 2022;65:103984. Declarations 18. Shobeiri P, Bagherieh S, Mirzayi P, Kalantari A, Mirmosayyeb O, Teixeira AL, Rezaei N. Serum and plasma levels of brain-derived neurotrophic factor Ethics approval and consent to participate in individuals with eating disorders (EDs): a systematic review and meta- Not applicable. analysis. J Eat Disord. 2022;10(1):1–8. 19. Shobeiri P, Karimi A, Momtazmanesh S, Teixeira AL, Teunissen CE, van Consent for publication Wegen EE, Hirsch MA, Yekaninejad MS, Rezaei N. Exercise-induced Not applicable. increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: a systematic review and meta-analysis of Competing interests exercise intervention trials. PloS one. 2022;17(3):e0264557. The authors declare that they have no competing interests. 20. Khalaji A, Behnoush AH, Shobeiri P, Saeedian B, Teixeira AL, Rezaei N. Asso- ciation between brain-derived neurotrophic factor levels and obstruc- tive sleep apnea: a systematic review and meta-analysis. Sleep Breath. Received: 31 October 2022 Accepted: 26 February 2023 2022;17:1–3. 21. 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Journal
Advances in Rheumatology – Springer Journals
Published: Mar 6, 2023
Keywords: Brain-derived neurotrophic factor; BDNF; Systemic lupus erythematous; SLE; Lupus; Neuropsychiatry lupus