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Indonesian Journal of Rheumatology Vol 14 Issue 2 20221. Introduction
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with diverse clinical manifestations in association with autoantibodies to components of the cell nucleus.1 This production of autoantibodies is directed towards self-molecules found in the nucleus, cytoplasm, or surface of cells, creating an immune complex that will be deposited in various organs and causing tissue damage.1 This
disease is a multisystem disease that involves the important role of hyperactivity of B cells and T cells as well as abnormalities of immune complexes clearance and apoptotic materials.2,3
B Cell activating factor (BAFF) is a superfamily of Tumor Necrotizing Factor (TNF), the cytokine that plays a role in the pathogenesis of SLE.3 It acts as a crucial factor in regulating B cells which affect the proliferation, differentiation, maturity, activation, and
B-Cell Activating Factor Profile and Quality of Life in Systemic Lupus Erythematosus Patients
Andri Reza Rahmadi1, Habib Burahman2, Nadia Gita Ghassani3, Rachmat Gunadi Wachjudi1, Laniyati Hamijoyo1,3*
1Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran /Hasan Sadikin General Hospital, Bandung, Indonesia
2Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia
3Lupus Study Group, Immunology Study Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
ARTICLE INFO Keywords:
BAFF MEX-SLEDAI Quality of life
Systemic lupus erythematosus
*Corresponding author:
Laniyati Hamijoyo
E-mail address:
All authors have reviewed and approved the final version of the manuscript.
https://doi.org/10.37275/IJR.v14i2.204
A B S T R A C T
Background: B-Cell Activating Factor (BAFF) is a cytokine that plays a role in systemic lupus erythematosus (SLE) pathogenesis. BAFF increases B cell function, which will affect disease activity. In addition to decreasing disease activity, good quality of life (QoL) is one of the goals to be achieved in SLE therapy, which is also affected by disease activity. The purpose of this study is to know the correlation of the BAFF profile with the QoL of SLE patients.
Methods: This was a cross-sectional study using secondary data from a previous study. The subjects of this study were SLE patients who had visited the rheumatology outpatient clinic or were hospitalized in Hasan Sadikin Hospital Bandung from September 2016 until February 2017. Subjects were asked to complete the Short Form-36 and measure their BAFF level in serum. Demographic data were collected, and disease activity data were assessed by Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). The statistical analysis used in this study was the Spearman test. Results: There was a positive correlation between BAFF and MEX- SLEDAI (r 0.238, p-value 0.038). There was also a negative correlation between MEX-SLEDAI and PCS, as well as the MCS score (r -0.392 and - 0.371, p-value <0.05). Conclusion: BAFF levels will increase in higher disease activity which will affect a poorer quality of life.
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Journal Homepage: https://journalrheumatology.or.id/index.php/IJR
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survival of the B cells.4 BAFF has the ability to pass through the protein membrane and can be detected in the serum of patients with the enzyme-linked immunosorbent assay (ELISA) method. BAFF levels have been shown to be elevated in the serum of patients suffering from autoimmune diseases, such as SLE, rheumatoid arthritis, and Sjogren syndrome. 4,5
Quality of life (QoL) is a subjective and heterogeneous concept of well-being correlated with a number of factors, such as duration of illness, use of medications, and stress events, that are now considered of great relevance to measuring the outcomes of chronic disease.6 It also has become central to evaluating the effectiveness of treatments as well.6 With no exception, this also occurred in SLE.
Systemic lupus erythematosus affects patients' QoL in all kinds of aspects, extending from physical, psychological, and social to economic aspects.7,8
There is a known correlation between the quality of life and disease activity. Impairment of some aspects of quality of life is associated with persistent disease activity.9 Since disease activity can be predicted with the increasing of BAFF levels,4,10 there is a possible association between BAFF and quality of life.
However, studies discussing BAFF in Indonesia are only a few. Moreover, there are not any studies yet about the correlation of BAFF with quality of life. The purpose of this study is to know the correlation of the BAFF profile with the quality of life of SLE patients.
2. Methods
This was a comparative study with a cross- sectional approach using secondary data from Hasan Sadikin Lupus Registry Cohort and a previous BAFF study. The subjects of this previous study were SLE patients who had visited the rheumatology outpatient clinic or were hospitalized in Hasan Sadikin Hospital Bandung from September 2016 until February 2017.
The inclusion criteria of this study were (1) all SLE patients who were at least 14 years old, (2) had the ability to communicate verbally, (3) were able to write and read, and (4) agreed to participate in this study.
This study excluded SLE patients (1) who had other
comorbid diseases such as Human Immunodeficiency Virus (HIV) infection or currently had been taking antiretroviral medicine, Hepatitis C Virus (HCV) infection, cirrhosis hepatic, chronic lymphocytic leukemia (CLL), and lastly, Hodgkin and Non-Hodgkin malignant lymphoma (NHML) and (2) was an active smoker. These exclusion criteria were based on previous studies that reported an elevated level of BAFF in these diseases, which could lead to bias in this study.5 Population who smoke also would have a higher serum BAFF level due to particles from cigarette smoke that could stimulate respiratory tract epithelium to express BAFF and induce inflammation.11
This study collected secondary data consisting of serum BAFF level and quality of life of patients based on Short Form-36 (SF-36) from the previous study.
SF-36 was a health survey questionnaire widely used to evaluate QoL as a subjective perception regarding psychological and physical limitations that were caused by musculoskeletal diseases.12 SF-36 consisted of 36 items that were categorized into two main components; Physical Component Summary (PCS) and Mental Component Summary (MCS).
Samples were taken using stratified random sampling with minimum samples of 76 patients after being calculated using the sample size formula. Three milliliters of blood from 76 samples were drawn intravenously and then centrifuged at the speed of 3000 rpm for 15 minutes. A serum was formed and then stored in a microtube under -20°C temperature until all serums were collected. BAFF level was then measured simultaneously with the ELISA method.
Demographic and disease activity data were also collected and assessed by Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI).
The statistical analysis used in this study was the Spearman correlation test.
3. Results
Seventy-six subjects were chosen to participate in this study. The mean age among all subjects was 30.6 years old, as shown in Table 1. Among 76 subjects,
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all subjects were female. Their average duration of disease was 40.8 months. Most of the subjects were housewives (55.2%), had high school as their last education (67.1%), and had medium income (63.1%).
The mean serum BAFF level was 15533.5, and meanwhile, mean PCS and MCS scores were 43.9 and 43.8, respectively.
As shown in Table 2, there was a lack of correlation between BAFF with PCS and MCS score (p-value
>0.05). On the other hand, there was a significant positive correlation between BAFF and MEX-SLEDAI score (p-value 0.038). However, the correlation was weak (r=0.238). There was also a significant-but-weak correlation between MEX-SLEDAI and PCS, as well as the MCS score (r= -0.392 and -0.371, respectively) shown in Table 3. The negative correlation indicated that as the MEX-SLEDAI score increased, the PCS and MCS scores of QoL would be lowered.
Table 1. Demographic of SLE patients.
Table 2. Correlation of BAFF with QoL and MEX-SLEDAI in SLE patients.
BAFF
Coefficient correlation (r) p-value R2
PCS -0.17 0.883 0.029
MCS -0.142 0.220 0.02
MEX-SLEDAI 0.238 0.038 0.056
Note: p-value analysis was done by the Spearman test.
BAFF : B Cell activating factor, QoL: Quality of Life, SLE: Systemic lupus erythematosus, PCS: Physical Component Summary, MCS: Mental Component Summary, MEX-SLEDAI: Mexican Systemic Lupus Erythematosus Disease Activity Index.
Characteristics Total
N= 76
Age (years), Mean±SD 30.6 ± 9.8
Gender, n (%)
Female 76 (100)
Duration of disease (months), mean 40.8 ± 41
Occupation, n (%)
Unemployed 14 (18.4)
Housewives 42 (55.2)
Students 7 (9.2)
Civil servants 1 (1.3)
Private sector 6 (7.8)
Teacher 4 (5.2)
Entrepreneur 2 (2.6)
Education, n (%)
Elementary school 2 (2.6)
Middle school 9 (11.8)
Senior high school 51 (67.1)
Diploma 4 (5.2)
Undergraduate 9 (11.8)
Magister 1 (1.3)
Income, n (%)
Low (< IDR 1,750,000) 27 (35.5)
Medium (IDR 1,750,000 – 4,000,000) 48 (63.1)
High (≥ IDR 4,000,000) 1 (1.3)
Serum BAFF level, mean 15533.5
PCS score, mean 43.9
MCS score, mean 43.8
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Table 3. Correlation of MEX-SLEDAI and QoL in SLE patients.
MEX-SLEDAI
Coefficient correlation (r) p-value R2
PCS -0.392 <0.001 0.153
MCS -0.371 0.001 0.137
Note: p-value analysis was done by the Spearman test.
MEX-SLEDAI: Mexican Systemic Lupus Erythematosus Disease Activity Index, QoL: Quality of Life, SLE:
Systemic lupus erythematosus, PCS: Physical Component Summary, MCS: Mental Component Summary.
4. Discussion
There are several reports suggesting a central role of BAFF in the pathogenesis of SLE.3,4 Given the apparent connection between BAFF and SLE pathogenesis, we try to elucidate the link between BAFF and quality of life without putting disease activity aside as one of the contributing factors.
Findings in this study showed that there was a lack of correlation between BAFF levels and quality of life.
However, this study reported that there was a significant positive correlation between BAFF and MEX-SLEDAI score. The increase in serum BAFF levels correlated with the increase in MEX-SLEDAI score, which portrayed the more severe disease activity. This is in accordance with findings from previous studies.
There have been a lot of reports suggesting an increase in BAFF levels in active SLE.10,13-16 Petri et al.
reported that BAFF levels predicted increases in SLE disease activity, supporting the notion that elevated BAFF has a role as a biomarker for current and/or future SLE disease activity.10 In another study, Petri et al. also reported using multivariate analysis that elevated baseline serum BAFF concentration (≥2ng/mL) was predictive of moderate-to-severe SLE flares in patients receiving prednisone and hydroxychloroquine or any other immunosuppressive drugs.14 George-Chandy et al. also showed an elevation BAFF level of cerebrospinal fluid in SLE patients.15 This might be due to the production of BAFF by astrocytes in the brain or immune cells within the central nervous system. Aside from that, it may also be caused by serum BAFF that succeeded in penetrating the blood-brain barrier. Both of them portray the neuropsychiatric manifestation of SLE,
which indicates the severity of SLE activity. Strand et al. also reported that out of the two groups of SLE patients who received anti-BAFF (Belimumab) therapy for 52 weeks and 76 weeks, both groups achieved improvement in their disease activity.13
This study also found that there was a significant negative correlation between MEX-SLEDAI and PCS, as well as the MCS score of QoL, which indicated that disease activity might be a predictor of quality of life.
This is in accordance with findings from C. C. Mok et al., who reported that SF-36 scores in SLE patients correlated inversely with Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), a known parameter for assessing disease activity.9 Low score of SF-36 indicates poor quality of life, which is correlated with a high score of SDI that signifies the activity of SLE. Persistent disease activity is associated with deterioration in certain domains of the SF-36.9 As we discussed earlier, disease activity status will affect the quality of life, especially in SLE patients.9,17 Therefore, BAFF levels will also increase in a patient with poor quality of life since BAFF is also increased in more severe disease activity.
Limitations of this study were as follows: (1) Factors that could affect both disease activity and quality of life, such as selection of medication used and type of organ involved in SLE manifestation, were not accounted for in this study. All of the subjects in this study had received previous treatment with steroids and immunosuppressants such as azathioprine, methotrexate, cyclosporine, and cyclophosphamide.
(2) The findings in this study are based on the measurement of BAFF levels in plasma. However, lupus nephritis contributes to more severe disease activity, and it may increase BAFF excretion in urine.
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Future analyses of urine BAFF protein may prove to be highly informative.10 (3) This study used a cross- sectional design which could only assess the effect of BAFF towards QoL in a single period of time. A subsequent study with a cohort method for the following visits of the patients is necessary to know the BAFF role in QoL.
5. Conclusion
The importance of this study is to add knowledge about the BAFF profile on SLE patients regarding their quality of life. The correlation between BAFF and QoL in this study was strongly related to the role of disease activity as an inseparable link between those two. This study can become a preliminary study to conduct a cohort study to follow up on patients' QoL and their BAFF levels in SLE patients.
Since there is a possible correlation between BAFF and QoL, BAFF level measurement and health questionnaires about quality of life can be applied as one of the optimum management for SLE patients.
The apparent role of increased BAFF in SLE disease activity suggests that an anti-BAFF therapeutic approach may prove to be useful in controlling disease activity 10 and eventually will enhance the quality of life in SLE patients itself. The use of BAFF antagonist as a potential therapeutic approach to increase the quality of life in SLE might be rational as the BAFF level appears to be associated with quality of life in this study.
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