In the present study, we retrospectively analyzed 125 patients with SLE and found that the prevalence of leukopenia, neutropenia, and lymphopenia was 40.0, 20.8, and 55.2%, respectively. Moreover, the median leukocyte count, neutrophil count, and lymphocyte count in the corresponding hemocytopenia group were only 47.06, 40.58, and 30.00% of the healthy control group, respectively. Therefore, leukopenia, neutropenia, and lymphopenia are not only common clinical manifestations of SLE but also the degree of reduction in the number of leukocytes, neutrophils, and lymphocytes is very remarkable.
The prevalence of leukopenia in patients with SLE reported in the literature varies greatly from 22 to 60% [9, 10]. Leukopenia is usually caused by either or both lymphopenia and neutropenia. Low lymphocyte count commonly occurs in SLE, with a prevalence ranging from 15 to 93%, while neutropenia was described in 4.5% to 47% of patients [1, 9,10,11,12]. The significant differences in the prevalence of leukopenia, neutropenia, and lymphopenia among these studies may be related to the number of cases, race, region, treatment, and research method used. First, the prevalence of lymphopenia varies among ethnic populations [3, 13, 14]. This study focused on the characteristics of leukopenia in Han patients with SLE, so only the Han population was included. Second, the prevalence of leucopenia and neutropenia in the treated group was significantly lower than that in the untreated group, suggesting that the treatment reduced the prevalence of leukopenia and neutropenia. Third, accompanying diseases may affect the leukocyte levels. In order to detect the prevalence of leukopenia more accurately, we excluded patients with infection, liver cirrhosis, malignant tumors, other connective tissue diseases, and so on. Finally, this study confirmed that lymphocyte count was negatively correlated with the SLEDAI 2000 score, so the disease status of the included patients may affect the prevalence of lymphopenia.
Leukopenia was positively associated with anti-dsDNA antibody, anti-ribosomal P protein antibody, neutropenia, lymphopenia, and thrombocytopenia in the present study, and patients with leukopenia developed decreased neutrophil counts, lymphocyte counts, platelet counts, and complement C3 levels. In another study, SLE patients with leukopenia also had an increased incidence of lymphopenia, thrombocytopenia, hemolytic anemia, anti-dsDNA antibody positivity, lupus anticoagulant and psychosis . Recent research showed that leukopenia was associated with anti-dsDNA antibody positivity, low complement and ESR ≥ 25 mm/H . We speculated that the correlation between leukopenia and other parameters may be due to the fact that neutropenia or lymphopenia was related to these parameters.
The present study showed that neutropenia was not associated with any of the antibodies studied, but was related to several clinical parameters, including lymphocytes, platelets, complement C3, and cylindruria. In a multivariate analysis, decreased platelet count and lymphocyte count, as well as the presence of cylindruria were identified as independent risk factors for neutropenia. Martinez-Banos et al. carried out a prospective study that included 33 SLE patients with moderate to severe neutropenia (< 1000/μl) . Patients with neutropenia had a lower number of lymphocytes, hemoglobin, and platelets, but no differences in antinuclear antibodies were detected . There was also no significant association between any autoantibody against nuclear antigens and neutropenia in a study including 82 lupus erythematosus patients . A study including 208 SLE patients with neutropenia and 779 SLE patients without neutropenia showed that neutropenia was significantly associated with thrombocytopenia, lymphopenia, and low levels of complement C3 as determined in a multivariate analysis, which was similar to our results .
Anti-ribosomal P protein antibody has been reported to be associated with diffuse psychiatric/neuropsychological syndromes in SLE, and was also found to be associated with lymphopenia in several studies [20,21,22,23,24]. In a dataset (GIPT) originating from patients with SLE from six European tertiary centers, only anti-Sm antibody was associated with lymphopenia in a univariate model, while antibodies targeting other nuclear antigens were not associated with lymphopenia . A cross-sectional, well-characterized SLE dataset from Sweden presented that anti-DNA antibody and anti-Sm antibody were associated with lymphopenia as determined using univariate and multivariable analyses . In the present study, lymphopenia was significantly positively associated with anti-dsDNA antibody and anti-ribosomal P protein antibody, and multivariable analysis showed that anti-dsDNA antibody was an independent risk factor for lymphopenia.
Compared with neutropenia, lymphopenia showed a better correlation with the disease activity parameters of SLE, including the C3, C4, and SLEDAI 2000 scores, which was consistent with the results from the GIPT and Sweden SLE datasets. Moreover, in patients with lymphopenia, leukocyte count, neutrophil count, and platelet count decreased, and the presence of cylindruria increased. A multiethnic, longitudinal outcome study from the United States showed that lymphopenia was found to be positively associated with renal involvement, leukopenia and thrombocytopenia . A GIPT and Sweden SLE dataset observed that SLE patients with lymphopenia were more likely to have leukopenia, thrombocytopenia, and neurological manifestations . In addition, Spearman rank correlation analysis showed that the lymphocyte count was negatively correlated with the SLEDAI 2000 score in the present study. Therefore, the results of the above studies, including ours, are consistent despite some differences, suggesting that lymphopenia is associated with systemic damage and disease activity in SLE. In addition, the present study found that the lymphocyte levels of SLE patients without lymphopenia were still lower than those of healthy controls, so even if the lymphocytes of SLE patients are normal, the low level of normal lymphocytes may also indicate SLE disease activity.
Skare et al. found that Coombs’ test was positive in 12.8% of SLE samples studied, and was independently associated with hemolytic anemia, anti-RNP antibody and anti-SSB antibody . In the present study, the positive rate of Coombs’ test was also 12.8%, and there was a positive correlation between Coombs’ test and lymphopenia, but we did not find any description of this relationship previously detected, so the relationship between Coombs’ test and lymphopenia is worthy of further study.
Certain limitations of this study must be acknowledged. First, this was a cross-sectional study, which may have led to the lower prevalence of leukopenia, neutropenia, and lymphopenia. Second, this was a single-center study of the Chinese Han population, so the results of this study may not be suitable for all patients with SLE. Finally, the size of this cohort was small, and the results may be biased; thus, a larger trial is needed to further confirm these results.