Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies.

OBJECTIVE: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. METHODS: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. RESULTS: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. CONCLUSIONS: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.

Patient and provider perceptions of a novel cognitive functioning report for patients with systemic lupus erythematosus: a qualitative study.

OBJECTIVE: To determine whether and how cognitive assessment data should be included in a report for patients with SLE and their providers. METHODS: Leveraging experiences from prior studies, we created a cognitive report that included a hypothetical patient's results on tests of multiple domains based on the NIH Toolbox Fluid Cognition Battery. In focus groups that comprised patients with SLE (two groups) and their providers (two groups), feedback was sought on the presentation of results as well as the potential value of the report in the clinical setting. RESULTS: Feedback regarding the presentation of the report was generally positive. Both patients with SLE and their providers liked its simple graphics and use of a colour-gradated scale to indicate performance. However, both groups stressed the importance of using non-stigmatising language in describing results. Several potential purposes of the report, including distinguishing cognitive versus other issues, explaining cognitive challenges, improving patient-provider interactions, guiding decision-making, improving functioning or preventing impairment and tracking cognitive function over time, were noted by the participants. Potential barriers, such as inadequate clinical staffing or time and lack of potential treatments for identified issues, were also discussed. CONCLUSION: In this exploratory study, we found that both patients with SLE and their providers were receptive to the idea of a patient-friendly report of cognitive test results. This study provides important information to guide future pragmatic research to optimise the delivery of cognitive information to patients with SLE.

Collagen Type III and VI Remodeling Biomarkers Are Associated with Kidney Fibrosis in Lupus Nephritis.

Background: Lupus nephritis (LN) occurs in <40% of patients with SLE. Reliable biomarkers of kidney damage are needed to identify patients with SLE at risk of developing LN to improve screening, treat the disease earlier, and halt progression to kidney failure. Novel biomarkers of extracellular matrix remodeling were evaluated as markers of kidney fibrosis and disease activity in patients with LN. Methods: Biomarkers of the interstitial collagen type III (PRO-C3) and type VI (PRO-C6) formation and of collagen type III (C3M) degradation were evaluated in the serum and urine of 40 patients with LN, 20 patients with SLE but without LN, 20 healthy controls, and ten biopsy controls (histologic kidney inflammation/damage without SLE). Their association with histologic markers of interstitial fibrosis and tubular atrophy, with inflammatory cell infiltration and with disease activity and chronicity in the patients with LN was assessed. Results: Despite PRO-C3 (serum) and PRO-C6 (serum and urine) being significantly elevated in patients with LN compared with healthy controls, the markers did not differentiate patients with LN from those with SLE. C3M (urine) levels were not different in LN compared with the other groups. C3M (urine) strongly correlated and PRO-C6 (serum and urine) inversely correlated with kidney function (eGFR). The biomarkers of interstitial collagen turnover PRO-C6 (serum) and C3M (urine) correlated with histologic markers of interstitial fibrosis, tubular atrophy, and monocyte infiltration. Conclusions: Noninvasive collagen turnover biomarkers are promising tools to identify patients with SLE with kidney histologic modifications.

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes.

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05-9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34-1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59-0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD.

Production of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta by human polymorphonuclear neutrophils stimulated with Porphyromonas endodontalis lipopolysaccharide.

This study was undertaken to investigate the capacity of polymorphonuclear neutrophils (PMNs) to secrete Macrophage Inflammatory Protein (MIP)-1alpha and MIP-1beta after stimulation with Porphyromonas endodontalis lipopolysaccharide (LPS). Escherichia coli LPS was used as a positive control. Venous blood was collected and PMNs were isolated from healthy volunteers. Cells were cultured with various concentrations of LPS for different periods of time. Cell supernatants were assayed by enzyme-linked immunosorbent assay. The levels of chemokine secretion in PMNs stimulated with each LPS were found to be significantly higher than in the unstimulated control cells (p < 0.05), and this expression occurred in a time- and dose-dependent manner. E. coli LPS induced higher levels of cytokines than P. endodontalis LPS. These findings demonstrated that P. endodontalis LPS is capable of stimulating PMNs to produce chemotactic cytokines and suggested that PMNs stimulated with P. endodontalis LPS may play a crucial role in the inflammatory and immunopathological reactions of pulpal and periapical diseases.

Tissue levels of matrix metalloproteinases in pulps and periapical lesions.

The purpose of this study was to evaluate the tissue levels of matrix metalloproteinase (MMP)-1, -2, -3 and their distributions in inflamed human dental pulps and periapical lesions. Samples were subjected to enzyme-linked immunosorbent assay and/or immunohistochemistry by using specific antibodies to MMP-1, -2, and -3. Results from enzyme-linked immunosorbent assay were analyzed by using the Mann-Whitney U test and presented as p values. The concentrations of MMP-1 in all experimental groups were significantly higher than in the control (p < 0.05). The acute pulpitis and control groups were significant different in terms of their MMP-2 levels (p < 0.05). The concentration of MMP-3 in acute pulpitis was significantly higher than the control and chronic pulpitis groups (p < 0.05). Immunohistochemically, MMP-1 and MMP-3 were localized in the infiltrating neutrophils, macrophages, and extracellular matrix of the acute pulpitis group. These results suggest that MMPs play an important role in the pulp tissue destruction of acute, inflamed pulp.

T lymphocyte subpopulations and interleukin-2, interferon-gamma, and interleukin-4 in rat pulpitis experimentally induced by specific bacteria.

The objective of this study was to investigate the expression of surface markers on T lymphocytes and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. Pulpal inflammation was experimentally induced in rat mandibular incisors by drilling, without coolant, to open pulp chambers. Streptococcus mutans (S. mutans group), Porphyromonas endodontalis (P. endodontalis group), and a sterile cotton pellet only (control group) were inoculated in the canal. The expression of CD25 and CD54 on CD4+, and CD8+ lymphocytes in pulp tissues was determined by using a flow cytometer. The levels of interleukin (IL)-2, interferon (IFN)-gamma, and IL-4 were measured by ELISA. Flow-cytometric analysis showed that the mean ratio of CD4+:CD8+ was 0.96 in the control group, 0.99 in the S. mutans group, and 0.52 in the P. endodontalis group. An increase in CD25 and CD54 expression on CD4+ T lymphocytes was related to the bacterial infection (p < 0.05) and accompanied an increase in IL-2 concentration. The higher concentration of IFN-gamma than IL-4 in the P. endodontalis group suggested a Th1 reaction in the early stage of pulpal inflammation induced by P. endodontalis.