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Indonesian Journal of Rheumatology Vol 14 Issue 1 20221. Introduction
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by heterogeneous, multisystem involvement, and the production of an array of autoantibodies. SLE has various clinical and serological manifestations that start from low to high disease activities.1 The prevalence and incidence of SLE vary widely based on population and the methodology used in diagnosing SLE, epidemiological
data shows that the incidence is 1-25 cases per 100,000 population in the world.2 The course of SLE is characterized by exacerbations and remissions, requiring close monitoring of disease activity.
Evaluation of disease activity is useful as a guide in administering therapy. The mechanism of hematological abnormalities in SLE patients can be caused by disease activity or side effects of the drugs.
The main mechanism in this disease activity is an
Is There Any Correlation between Anti-Ro 52 Antibody Level with Hematological Abnormalities in Systemic Lupus Erythematosus?
Andiyang R. Diredja1, Amaylia Oehadian2*, Laniyati Hamijoyo3
1Department of Internal Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, Indonesia
2Division of Hematology and Oncology Medic, Department of Internal Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, Indonesia
3Division of Rheumatology, Department of Internal Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, Indonesia
ARTICLE INFO Keywords:
Anti-Ro 52 antibody level Disease activity
Haematological abnormalities SLE
*Corresponding author:
Amaylia Oehadian
E-mail address:
All authors have reviewed and approved the final version of the manuscript.
https://doi.org/10.37275/IJR.v14i1.186
A B S T R A C T
Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with various clinical and serological manifestations.
Previous studies have shown conflicting results about the association of anti- Ro 52 autoantibodies with hematological abnormalities in SLE. We investigated the correlation between anti Ro 52 autoantibody with anemia, leucopenia, and thrombocytopenia in patients with SLE. Methods: Sixty-two bio archives serum of an SLE patient at the Division of Rheumatology, Department of Internal Medicine, Hasan Sadikin General Hospital, Bandung, Indonesia from 2017 to 2019 were enrolled in the study. Anti-Ro 52 levels were examined using the ELISA method. The clinical data, treatment, and hematology paparametersere were analyzed retrospectively.
Results: Among 62 bio-archive serum, four subjects were excluded because of incomplete data. Fifty-eight patients, all females were enrolled. We identified 57 (98.3%) subjects corticosteroid, 31 (53.4%) azathioprine and 28 (48.3%) chloroquine. A correlation coefficient of anti-Ro 52 levels and hemoglobin, leukocyte and platelets were -0.037 (p = 0.391), 0.065 (p = 0.315) and 0.092 (p = 0.246), respectively. Conclusion: No correlation was found between anti Ro 52 antibody levels with haematological abnormalities in patients with SLE. Further studies need to evaluate whether other antibodies play important role in haematological abnormalities in SLE.
Indonesian Journal of Rheumatology
Journal Homepage: https://journalrheumatology.or.id/index.php/IJR
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aberrant autoimmune response to antigens.3 Bone marrow suppression is the side effect of drugs that play a role in causing hematological abnormalities in SLE patients.4
Anti-Ro antibodies are one of the antinuclear antibodies that can be found in 5-11% of SLE patients.
Anti-Ro antibodies are known as ribonucleoprotein complexes consisting of small single-chain RNAs with one or more peptides. Anti-Ro has two types of proteins, namely Ro 52 which plays a role in protein ubiquitination, pro-inflammatory and apoptotic mechanisms, and Ro 60 which plays a role in RNA degradation and is believed to have an important function in cell defense after ultraviolet radiation.5 Ro52 is more expressed in peripheral blood mononuclear cells (PBMC), and functions as an E3 ubiquitin ligase that can activate nuclear factor kappa-B kinase subunit beta (IKBB), and suppress nuclear factor kappa-B (NFKB) proinflammatory signals.6 If autoreactivity occurs there will be an increase in apoptosis and suppression of cell growth.
Previous studies have shown conflicting results about the association of anti-Ro 52 autoantibodies with haematological abnormalities in SLE. The aim of this work was to analyze the correlation between anti-Ro 52 antibody levels with anemia, leucopenia, and thrombocytopenia in SLE patients.
2. Methods
Patients and serum samples
Sixty-two serum of SLE patients at the Division of Rheumatology, Department of Internal Medicine, Hasan Sadikin General Hospital, Bandung, Indonesia from 2017 to 2019 were enrolled in the study. The Lupus Registry Database was used to identify adult (>
18-year-old) patients in Hasan Sadikin General Hospital who were diagnosed with SLE based on the
American College of Rheumatology (ACR) 1997.
Patients were excluded if they had an infection, history of transfusion, bleeding, overlap syndrome, and uncompleted data. Anti-Ro 52 was examined using Assay Max Human Ro 52 ELISA Kit. The clinical data, treatment, and haematology parameters were analyzed retrospectively. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used for measuring the activity of SLE. High activity lupus is defined as a SLEDAI score >11. A score of 6- 10 represents moderate activity lupus, a score of 1-5 indicates mild activity and a score of 0 represents no activity of lupus.7
Statistical analysis
We calculated Spearman rank correlation coefficients for each haematological abnormality and anti-Ro 52 antibody levels. Results were considered statistically significant when the p-value was < 0.05.
Statistical analysis was performed using SPSS statistical software version 26.0 package.
3. Results
Baseline characteristics
Among 62 bio-archives serum, four subjects were excluded because of incomplete data. Fifty-eight patients (aged between 23-65 years) all females were enrolled. Most of the subjects had low disease activity compared with high disease activity (52/58 subjects (89.6%) vs 2/58 subjects (3.4%), respectively). Almost the subjects received therapy, there were corticosteroids (98.3%), chloroquine (48.3%), and azathioprine (53.4%). The median value of anti-Ro 52 antibody level was 3.63 ng/ml, the level of haemoglobin was 11.8 g/dl, leukocyte count was 7.082 x 103/mL and platelets count was 284.5 x 103/mL (Table 1).
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Table 1. Baseline characteristic
Characteristic n=58
Gender, n (%)
Female 58 (100)
Age (years)
Median (IQR) 33 (10.75)
Duration of disease (months)
Median (IQR) 48 (60)
Disease Activity, n (%) 0
1-5 6-10
>11
46 (79.3) 6 (10.3)
4 (6.8) 2 (3.4) Therapy, n (%)
Corticosteroid Chloroquine Azathioprine
Anti-Ro 52 Antibody (ng/ml) Median (IQR)
Hematology parameters
Hemoglobin (g/dl), median (IQR) Leukocyte x 103/mL, median (IQR) Platelets x 103/mL, median (IQR)
57 (98.3) 28 (48.3) 31 (53.4) 3.63 (23.83)
11.8 (2) 7.082 (4.55) 284.5 (111.25) *n: frequency, IQR: Interquartile range
Correlation Anti Ro 52 with haematological abnormalities
Correlation analysis using Rank Spearman showed that there was no correlation between anti-
Ro 52 antibody levels with haemoglobin levels, leukocyte counts and platelet counts. The correlation coefficient were - 0.037 (p = 0.391), 0.065 (p = 0.315) and 0.092 (p = 0.246), respectively (Figure I).
Figure 1. Scattered plot correlation of Anti Ro 52 antibody with haematological parameter
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4. Discussion
Previous studies have shown controversial data regarding the relationship between anti-Ro levels and hematological abnormalities in SLE patients. This is because the function of Ro52 has an important role in regulating the formation of inflammatory cytokines and type I IFN in response to the activation of innate immunity, Tol-like receptors (TLR).8 This explains the difference in antibody levels in this study. The higher the disease activity, the higher the anti-Ro 52 antibody level, and vice versa. The results showed that there was no correlation between anti-Ro 52 antibody levels and hemoglobin levels, leukocyte counts, and platelet counts. This can be explained by the protective effect of antimalarial drugs that are known to play a role in the course of SLE, namely a decrease in antigen presentation and inhibition of Toll-like receptor (TLR) activation which causes a decrease in pro- inflammatory cytokines. Decreased LES activity in response to hydroxychloroquine treatment correlated with decreased production of IFN-.9 The subjects in this study had received therapy with steroids, immunosuppressive or cytostatic drugs. Besides that, a previous study showed that anti-Ro levels tend to decrease when patients have been treated with cytotoxic drugs.10
Our study found no correlation between anti-Ro 52 antibody levels and hematological abnormalities in SLE patients. This is supported by the study of Menendez et al. which found that there was no significant relationship between anti-Ro 52 with anemia and thrombocytopenia, but there was a significant relationship with leucopenia. In that study, they did not include all cytopenia conditions (thrombocytopenia and anemia hemolytic) to prevent confounding and treatment effects.11 Another similar study was conducted by Chelvi et al. the results of the study indicated that there was no relationship between anti-Ro 52 antibodies with anemia, leucopenia, and thrombocytopenia.12 This is different from the study conducted by Vila, et al. on 201 SLE patients which showed there was a relationship between anti-Ro antibodies and the incidence of anemia.13
Disease activity in our study was evaluated using SLEDAI. In our study, the majority score was < 1, which was found in 46 subjects (79.3%). This could be explained because most of our patients had received therapy such as steroids and other immunosuppressant drugs. In a previous study, Koelmeyer, et al. demonstrated the role of anti-Ro in SLE disease activity. Anti-Ro positive has an odd ratio (OR) of 1.9 (1.2-3.1) for high disease activity status (HDAS).14 The variation of anti-Ro antibody level in this study is due to the Ro 52 antigen binding to the Fc receptor area on isotypes 1, 2, and 4 IgG through the B30.2 domain. The significance of this event is still unknown, but there is a suspicion of an immunopathogenic relationship between Ro52 and anti-IgG autoantibodies in different individuals.15 The lowest level was found in subjects with low disease activity, while the highest level values were found in subjects with high disease activity. The variation in antibody level in this study also means that there is a regulation of the immune response to antigens and also indicates that the response is an antigen drive.
This Ro protein will also bind to the molecular complex hY RNA which can be found in erythrocytes and platelets.10
We acknowledge a number of limitations in our study. First, this study is a retrospective study that takes data from the LES registry of Hasan Sadikin Hospital. This causes selection bias due to incomplete data. Second, all subjects in this study were and had received therapy. Lastly, as many as 89.6% of the study population had a low disease activity that could affect the results of the study.
5. Conclusion
There is no correlation between anti-Ro 52 antibody levels and hematological abnormalities in SLE patients.
6. References
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