Dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies in rheumatic and musculoskeletal diseases patients with COVID-19.

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMD) may exhibit different immune responses to novel coronavirus (COVID-19) infection compared to healthy individuals. While previous studies have primarily investigated changes in COVID-19-related antibodies post-vaccination for RMD patients, this study sought to explore the dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies (NAb) in RMD patients after COVID-19 infection. METHODS: In this longitudinal study, we monitored the SARS-CoV-2 IgG antibodies and NAb levels in RMD patients and healthy controls (HC) at 60 and 90 days post-COVID-19 infection. Chemiluminescent immunoassay was used to detect the levels of novel coronavirus-specific IgG (anti-S1/S2 IgG) antibodies and NAb. RESULTS: A total of 292 RMD patients and 104 HC were enrolled in the study. At both the 60-day and 90-day post-COVID-19 infection, RMD patients exhibited significantly lower levels of anti-S1/S2 IgG and NAb than those in the HC group (p<0.001). The anti-S1/S2 IgG antibody levels remained relatively stable, while the NAb levels in RMD patients could vary greatly between the 60th and 90th days. A logistic regression analysis revealed that the prior administration of glucocorticoids (GC), immunosuppressants, and b/tsDMARDs stood out as independent risk factors associated with reduced anti-S1/S2 IgG and NAb levels, irrespective of the specific RMD subtypes. CONCLUSIONS: GC and anti-rheumatic medications can potentially alter the production of specific antibodies, especially NAb, in RMD patients post-COVID-19 infection. These findings emphasise the importance of continuous monitoring for NAb fluctuations in RMD patients following a COVID-19 infection.

Significant association of CD4+CD25+Foxp3+ regulatory T cells with clinical findings in patients with systemic lupus erythematosus.

BACKGROUND: Regulatory T (Treg) cells are one of the important mechanisms in maintaining self-tolerance and immune homeostasis. CD4+CD25+Foxp3+Treg is considered to have a role in the pathogenesis of systemic lupus erythematosus (SLE). However, the data reported is controversial, and a conclusive result has not been given thus far. The aim of the present study is to evaluate the role of CD4+Treg in SLE further. METHODS: The peripheral blood T cells (PBMCs) from patients with SLE and healthy controls were isolated, and followed by the isolation of CD3+T cells. The PBMCs were tested for the expressions of CD25 and Foxp3 molecules on the surface of CD4+T cells, and CD3+T cells were tested for their cytokine expressions including IFN-γ, TGF-ß, and IL-10, with the method of flow cytometry. The correlations of test results with clinical features of the disease were evaluated by linear correlation analysis. RESULTS: CD4+CD25+ Foxp3+Treg decreased in SLE patients and was correlated with the SLE Disease Activity Index (SLEDAI), and a few immunological abnormalities, including anti-dsDNA antibody positive, IgG increase and C3 decrease, and types of tissue damage, including leukocytopenia and kidney damage. IFN-γ+ cells in the CD4+CD25+T subset fresh-isolated from SLE patients increased slightly, but IFN-γ-producing response to stimulation in CD4+CD25+T subset of SLE decreased. The number of TGF-ß-producing cells in the CD4+CD25+T subset from SLE patients also decreased. While the percentages of CD4+CD25+IL-10+T subset in the CD3+T cells increased in SLE, however, these changes of cytokine expressions did not show any significant correlations with SLEDAI. CONCLUSIONS: There is clear and definite evidence from the present study indicating the important role of CD4+CD25+Foxp3+Treg in the pathogenesis of SLE, for the abnormalities in functional cytokine productions of the CD4+CD25+ T subset, and for the feasibility of a CD4+CD25+Foxp3+Treg- based immunotherapy in SLE.

Artery compliance in patients with rheumatoid arthritis: results from a case-control study.

Atherosclerosis is one of the most common complications of rheumatoid arthritis (RA). The objective of this study is to evaluate differences in large artery compliance (C1) and small artery compliance (C2) between RA and controls and evaluating factors associated with reduced compliance in the RA population. The profiling of large and small arterial compliance was analyzed in 185 RA patients and 88 healthy controls using Cardiovascular Profiling Instrument. The correlations of arterial compliance and the relevant clinical data were determined in these subjects. Then correlation analysis and regression analysis were performed to find whether rheumatoid arthritis patients have more risk factors than healthy controls in artery compliance and to explore the possible element involved in RA patients including traditional cardiovascular risk factors, RA disease-related factors, and the therapy. Compared with healthy controls, levels of C1 and C2 were significantly decreased in RA patients. Having adjusted the traditional risk factors associated with atherosclerosis, C1 and C2 decline was still a significant indicator in RA patients [odds ratio = 7.411(95%CI 3.275, 16.771) and 10.184(95%CI 4.546, 22.817)]. Using multi-factor regression analysis to adjust traditional risk factors for arterial compliance, we found that the levels of ESR was correlated with the abnormal large artery compliance [odds ratio = 1.021(95%CI 1.007, 1.035)]. The HAQ values and the current usage of leflunomide were correlated with the abnormal small artery compliance in RA patients [odds ratio = 1.161(95%CI 1.046, 1.289) and 6.170(95%CI 1.510, 25.215)]. The values of C1 and C2 are indicators of artery compliance in RA patients. ESR, HAQ values, and the usage of leflunomide might be possible risk factors of artery compliance. The evaluation of artery compliance could be an easy and reliable test that could help us to screen and predict cardiovascular disorders in RA patients.

High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent-onset rheumatoid arthritis patients.

BACKGROUND: We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients. OBJECTIVES: To investigate whether serum levels of HP are associated with the response of 12 weeks MTX therapy in recent-onset RA patients. METHODS: Sixty-nine active RA patients with recent onset (< 24 months) were treated with MTX. Clinical variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were tested at week 0 and week 12. RESULTS: After 12 weeks of MTX treatment, 34.7% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints [DAS-28] ≤ 3.2 and decrease > 1.2) and all others (65.2%) were defined as non-responders. The baseline HP mRNA in PBMCs from non-responders is significantly higher than those in responders (P < 0.05). Similar to mRNA expression, non-responders showed significantly elevated serum HP levels at baseline (369.9 ± 159.8 mg/dL) compared to those in responders (255.3 ± 143.9 mg/dL) (P = 0.01). Serum HP levels were decreased significantly from 255.3 ± 143.9 mg/dL at baseline to 186.4 ± 108.5 mg/dL at week 12 (P = 0.04) in responders, but remained at high levels in non-responders. CONCLUSIONS: High serum levels of HP at baseline are associated with inadequate response of 12 weeks MTX treatment in recent-onset RA patients. Further replication studies in larger samples are needed to validate HP as a potential predictive biomarker for response to MTX therapy in RA.

The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus.

To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control's serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas-FasL pathway.