scholarly journals Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia

1999 ◽  
Vol 58 (5) ◽  
pp. 309-314 ◽  
Author(s):  
P A Courtney ◽  
A D Crockard ◽  
K Williamson ◽  
A E Irvine ◽  
R J Kennedy ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Sun ◽  
Huijun Lai ◽  
Dong Shen ◽  
Pingping Wu ◽  
Jie Yang ◽  
...  

Both membrane-bound and soluble forms of costimulatory molecules play important roles in immune-regulatory networks. B7-H3, a member of the B7 family, has been found with aberrant expression in tumors and infectious disease. However, the significance of sB7-H3 expression in systemic lupus erythematosus (SLE) has not been investigated. Using the peripheral blood of 78 SLE patients, we established a comprehensive database containing clinical data and relevant laboratory tests. We found that sB7-H3 expression in SLE patients was significantly lower compared with the healthy individuals. In addition, sB7-H3 levels in the patients were positively correlated with the disease activity as indicated by SLE disease activity index score, rashes, fever, and inflammatory cytokines. Moreover, sB7-H3 was associated with the counts of red blood cells and hemoglobin. Our findings suggest that sB7-H3 might counteract the aberrant immune response and potentially serve as a monitoring indicator of disease progression and therapeutic target in SLE treatment.


2001 ◽  
Vol 10 (4) ◽  
pp. 179-189 ◽  
Author(s):  
Ewa Robak ◽  
Hanna Niewiadomska ◽  
Tadeusz Robak ◽  
Jacek Bartkowiak ◽  
Jerzy Z. Bloński ◽  
...  

Human Tγσ lymphocytes constitute from 1 to 15% of all peripheral blood lymphocytes. Recent work has demonstrated that this population plays a major role in the pathogenesis of infectious and immune diseases. Increased numbers of γσ T cells have been found in affected skin from systemic sclerosis and chronic cutaneous lupus erythematosus patients.In our study, we have determined the numbers of Tγσ lymphocytes and their subpopulations in peripheral blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy volunteers using flow cytometry and specific monoclonal antibodies. The same cells in uninvolved skin from SLE patients and human controls using immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain gene rearrangement was identified with primers for Vσ1, Vσ2 and Vσ3 by the polymerase chain reaction. Statistical analysis showed a significantly decreased number of γσ T cells in SLE patients (26.4 Ī 16.9/μl) compared with the control group (55.3 Ī 20.6/μl) (p<0.001). The number of Vσ2 TCR+ and Vγ9 TCR+ subpopulations was also lower in SLE patients than in healthy persons. No statistical correlation between disease activity and the number of γσ T cells was demonstrated. The percentage of T γσ lymphocytes in clinically normal skin from SLE patients was twice (22.0 Ī 9.4%) that found in the skin from healthy persons (11.1 Ī 5.5%) (p<0.002). Higher percentages of the Vσ2 TCR+ and Vγ9 TCR+ subpopulation of lymphocytes were found in the skin from SLE patients. We have also found positive correlation between the percentage of Tγσ lymphocytes in skin and the activity of SLE (r=0.594, p<0.001), and between subpopulation Vσ3 TCR+ and disease activity (r=0.659, p<0.001). In conclusion, the results of our studies demonstrate that, in patients with SLE, accumulation of Tγσ lymphocytes can be seen in clinically normal skin, and the percentage of these cells correlates with the activity of the disease.


2021 ◽  
Author(s):  
Wei Quan ◽  
Jingnan An ◽  
Gang Li ◽  
Guanghui Qian ◽  
Meifang Jin ◽  
...  

Abstract Background: Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect expression of the Th cytokines IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α in the peripheral blood of children with cSLE; clinical symptoms; and a disease index and discuss the relationship between the Th cell cytokine regulatory network and onset of systemic lupus erythematosus (SLE) in children and disease outcome.Methods: A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive cSLE group or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2K). Th cytokine profiles in peripheral blood of different groups were detected and analyzed.Results: The levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P<0.01 and P<0.01, respectively). The expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P<0.05, P<0.01 and P<0.05, respectively), but IL-22 expression was remarkably lower in the active cSLE group than in the healthy control group (P<0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P<0.05). The levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P<0.01 and P<0.05). In-depth analysis showed that the expression levels of IL-2 (r=0.382, P=0.028), IL-6 (r=0.514, P=0.002) and IL-10 (r=0.429, P=0.016) were positively correlated with disease activity. Conclusion: This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may open up potential new approaches for the diagnosis of cSLE.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Azita Sohrabian ◽  
Ioannis Parodis ◽  
Nellie Carlströmer-Berthén ◽  
Martina Frodlund ◽  
Andreas Jönsen ◽  
...  

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.


2015 ◽  
Vol 74 (7) ◽  
pp. 1474-1478 ◽  
Author(s):  
Tobias Alexander ◽  
Ramona Sarfert ◽  
Jens Klotsche ◽  
Anja A Kühl ◽  
Andrea Rubbert-Roth ◽  
...  

ObjectivesTo investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE).MethodsTwelve patients received a median of two (range 1–4) 21-day cycles of intravenous bortezomib (1.3 mg/m2) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti–double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity.ResultsUpon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined.ConclusionsThese findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1072.1-1072
Author(s):  
Y. J. Choi ◽  
E. K. Lee ◽  
M. S. Lee ◽  
C. H. Lee ◽  
C. H. Chung ◽  
...  

Background:Semaphorin has been found as a neuronal guidance molecule, but has recently been called “immune semaphorin”, as their critical role in immune cell activation, differentiation and migration has been revealed. In particular, class 4 semaphorin has been shown to contribute to lymphocyte activation and immune homeostasis.Objectives:This study was aimed to investigate the expression of neuropilin-1 (NRP-1), the receptor of class 4 semaphorin, in the murine mouse model of systemic lupus erythematosus (SLE) and the patients with SLE and the correlation between the expression of NRP-1 and disease activity of SLE.Methods:The expression of NRP-1 was measured in T cells in spleen and renal tissue in control mouse and TLR-7 agonist-induced lupus mouse by flow cytometry, PCR, and immunofluorescence (IF). CD4+ T cells from human peripheral blood were isolated to investigate the expression of NRP-1 in healthy control and the patients with SLE (n=40).Results:The frequency of NRP-1 positivity in CD4+ T cells in spleen was significantly higher in lupus mouse group (median [interquartile range]: 15.34 [14.84] %) compared to vehicle mouse group (4.0 [2.77]%). The quantitative analysis of fluorescense intensity in kidney stained for NRP-1 revealed the increased level in lupus group compared to vehicle group. The CD4+ T cells from peripheral blood mononuclear cells in the patients with lupus also showed significantly higher frequency of NRP-1 positive CD4+ T cells than those from healthy controls. Comparing the correlation of the expression of NRP-1 and disease activity with SLEDAI, C3, C4, and anti-DNA antibodies, the significant correlation between NRP-1 and disease activity markers were confirmed.Conclusion:Our results demonstrate that higher expression of NRP-1 in CD4+ T cells and its significant correlation with disease activity of SLE. These results indicate that pathologic contribution of NRP-1 in the pathogenesis of SLE and potential of targeting NRP-1 for the treatment of SLE.References:[1]Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases. Nat Rev Rheumatol. 2018 Jan;14(1):19-31.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document