Intracellular tubulo-reticular structures of peripheral blood mononuclear cells as an ultra-structural marker of disease activity in systemic lupus erythematosus: a pilot study.

OBJECTIVE: Under physiological stress, the membranes of organelles undergo conformational change to tubulo-reticular structures (TRS) for gaining survival advantage. We aim to explore whether TRS formation in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) correlates with more active disease where physiological stress prevails. METHODS: To mimic the intracellular impact of interferon-alpha (IFN-α) on lymphocytes, human B-lymphocyte cell line was stimulated by recombinant IFN-α in concentrations of 100, 1000 and 10 000 IU/mL for 72 h. TRS within the lymphocytes was then quantified by transmission electron microscopy (TEM). Upon confirming TRS formation under IFN-α influence, PBMCs of lupus patients were isolated, fixed and quantified for TRS under TEM. The frequency of TRS in lupus PBMCs was compared with that of healthy controls and correlated with the clinical SLE disease activity index (SLEDAI). RESULTS: After 72 h, an increase in TRS frequency was observed in a dose-response fashion when the human B-lymphocyte cell line was stimulated by increasing concentrations of IFN-α. In lupus patients, their PBMCs had a significantly higher TRS frequency than healthy controls (P = 0.037). The frequency of TRS was positively associated with the SLEDAI (Spearman ρ = 0.632, P = 0.012), which remained statistically significant after adjustment for daily prednisolone dose (Pearson r = 0.747, P = 0.002). CONCLUSIONS: While the clinical significance of TRS formation in lupus PBMCs deserves further investigation, these preliminary findings suggest a significant relationship between the disease severity of SLE and intracellular physiological stress. These results underscore the potential of TRS in PBMCs as an ultra-structural disease activity biomarker of SLE.

Clinical and psychosocial factors associated with depression and anxiety in Singaporean patients with rheumatoid arthritis.

AIM: To assess the frequency of, and factors associated with, depression and anxiety in Singaporean patients with rheumatoid arthritis (RA). METHOD: One hundred RA patients were recruited in a cross-sectional study. Socio-demographics, severity of anxiety and depression, disease activity, levels of serological markers and health-related quality of life were analyzed. RESULTS: Twenty-six percent presented with anxiety, 15% with depression and 11% with both. Univariate regression showed that age (P = 0.039), Disease Activity Scale (DAS-28) (P < 0.001), number of medications (P < 0.001) and rheumatoid factor (RF) (P < 0.001) were positively associated with severity of depression, while income (P = 0.001), education (P = 0.029), self-perceived social support (P = 0.007), Short form 12 (SF-12) physical health (P < 0.001) and SF-12 mental health (P < 0.001) were negatively associated with severity of depression. After adjustment for confounding factors in multivariate regression, income (ß = -0.347, P = 0.018), RF (ß = 0.304, P = 0.043) and SF-12 mental health (ß = -0.501 P = 0.001) remained significantly associated with depression. Univariate regression showed that DAS-28 (P = 0.009), number of medications (P = 0.004) and RF (P = 0.043) were positively associated with anxiety, while income (P = 0.022), self-perceived social support (P = 0.04), SF-12 physical health (P < 0.001) and SF-12 mental health (P < 0.001) were negatively associated with anxiety. After adjustment for confounding factors, no factors remained significantly associated with anxiety. CONCLUSION: Low income, high levels of RF and poor mental health were associated with depression in RA. Our findings may help to formulate depression screening strategies. Further research is required to identify the role of RF in depression.

Research on psychoneuroimmunology: does stress influence immunity and cause coronary artery disease?

This review addresses the importance of psychoneuroimmunology (PNI) studies in understanding the role of acute and chronic psychological stressors on the immune system and development of coronary artery disease (CAD). Firstly, it illustrates how psychological stressors change endothelial function and lead to chemotaxis. Secondly, acute psychological stressors lead to leukocytosis, increased natural killer cell cytotoxicity and reduced proliferative response to mitogens while chronic psychological stressors may lead to adverse health effects. This will result in changes in cardiovascular function and development of CAD. Thirdly, acute and chronic psychological stressors will increase haemostatic factors and acute phase proteins, possibly leading to thrombus formation and myocardial infarction. The evidence for the effects of acute and chronic psychological stress on the onset and progression of CAD is consistent and convincing. This paper also highlights potential research areas and implications of early detection of immunological changes and cardiovascular risk in people under high psychological stress.

Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression.

OBJECTIVE: Since mycophenolate mofetil (MMF) has emerged as an immunosuppressant for treating proliferative lupus nephritis, the role of cyclophosphamide (CYC)-containing regimens is being challenged. Efficacy data from randomized controlled trials (RCTs) and previous meta-analyses comparing these two agents for treating lupus nephritis have been inconsistent as they were heterogeneous in design and of small sample size. An updated meta-analysis is therefore required. METHODS: Publications in the English literature were searched with the keywords 'mycophenoate', 'mycophenolic', 'lupus nephritis', 'nephritis' and 'glomerulonephritis' for RCTs in electronic databases. Primary outcome was relative risk (RR) of renal remission at 6 months. Secondary outcome included RRs of mortality, development of end-stage renal failure (ESRF) and side effects. Meta-regression was performed to identify factors explaining the heterogeneity of the effect sizes. RESULTS: Ten eligible RCTs involving 847 patients were included. MMF offers similar efficacy in inducing renal remission as CYC (RR 1.052; 95% CI 0.950, 1.166) and the risks of death (RR 0.709; 95% CI 0.373, 1.347) and ESRF (RR 0.453; 95% CI 0.183, 1.121) were comparable. Significantly fewer patients receiving MMF developed amenorrhoea (RR 0.212; 95% CI 0.094, 0.479) and leucopenia (RR 0.473; 95% CI 0.269, 0.832) while the risks of herpes infection and pneumonia tended to be lower and that of diarrhoea appeared higher in the MMF groups. Meta-regression revealed that the non-white and non-Asian ethnicities contributed significantly to the heterogeneity of the effect sizes of renal remission. CONCLUSION: MMF offers similar efficacy in renal remission and survival as CYC. MMF appears safer than CYC in the treatment of proliferative lupus nephritis.