14-3-3η protein is associated with disease activity and osteoporosis in patients with rheumatoid arthritis.

Introduction: This study was designed to explore the potential association of serum 14-3-3η protein level with disease activity and bone mineral density (BMD) in Egyptian patients with rheumatoid arthritis (RA). Patients were recruited from the outpatient clinic at Mansoura University Hospital. Material and methods: One hundred eighty-eight patients with RA and 192 matched controls were enrolled. The rheumatoid arthritis activity parameters were evaluated in RA patients. Bone mineral density was measured. Serum levels of 14-3-3η protein and IL-6 were estimated for all participants by enzyme-linked immunosorbent assays (ELISA). Results: Rheumatoid arthritis patients had a significantly higher median serum 14-3-3η protein level compared to matched controls (p ≤ 0.05). Serum level of 14-3-3η protein was significantly correlated with DAS28-ESR (p ≤ 0.05) and serum IL-6 level (p ≤ 0.05). The rheumatoid arthritis-osteoporosis group had significantly higher serum 14-3-3η protein than the RA-osteopenia group and RA-control group. Similarly, the difference of the serum 14-3-3η protein between the RA-osteopenia group and the RA-control group was significant. In the linear regression analysis, the strongest factors that were associated with BMD in RA patients were the serum level of 14-3-3η protein (p ≤ 0.05), IL-6 (p ≤ 0.05) and DAS28-ESR (p ≤ 0.05). Conclusions: Serum level of 14-3-3η protein was significantly elevated in RA patients compared to controls and is significantly correlated with parameters of activity disease. The RA-osteoporosis group had significantly higher serum 14-3-3η protein than the RA-osteopenia group and RA-control group. Serum 14-3-3η protein can be a promising biomarker to reflect RA activity and predict presence of osteoporosis in RA patients.

Impact of IL-34, IFN-α and IFN-λ1 on activity of systemic lupus erythematosus in Egyptian patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune, multi-system inflammatory disease. Among cytokines involved in SLE pathogenesis, interferons (particularly IFN-α) and interleukin 34 play a pivotal role. Interestingly, the gene signatures of type III (IFN-λ1) and type I IFNs may overlap. Increased levels of IFN-λ also have been reported in SLE.Objectives: The aim of this study was to assess serum levels of IL-34, IFN-λ1, IFN-α and the relationship between these cytokines and clinical and laboratory parameters and response to treatment in a cohort of Egyptian SLE patients. MATERIAL AND METHODS: The study included 82 newly diagnosed SLE patients: male 17.1% (n = 14), female 82.9% (n = 68), mean age ±SD: 48.6 ±8.2 and 60 healthy subjects matched by age and gender as a control group. Medical history, physical examination and laboratory tests for confirming SLE diagnosis and assessment of disease activity were collected. The assessment of serum levels of studied cytokines were performed using the ELISA method.All studied patients after first cytokine evaluation were treated with a combination of antimalarial drugs, glucocorticosteroids and/or immunosuppressive drugs with follow-up after six months of treatment. RESULTS: In the SLE group the mean serum levels of IL-34, IFN-α and IFN-λ1 were 175.9 ±125.9 pg/ml, 109.3 ±32.5 pg/ml and 227.9 ±144.8 pg/ml respectively. These cytokine levels were significantly higher in the SLE group than in healthy controls. 39% of SLE patients (n = 32) had SLAM > 6 and 26.8% (n = 22) had SLEDAI >6. There were 21 SLE patients (25.6%) with lupus nephritis.IL-34 and IFN-λ1 were positively correlated with anti-dsDNA antibodies but negatively correlated with C3 complement component (p ≤ 0.05). IL-34, INF-α and IFN-λ1 were significantly higher in lupus nephritis patients, and correlated with poorest response to treatment.IL-34 and IFN-λ1 were correlated with higher SLAM > 6 and SLEDAI > 6 results; there was no such correlation between IFN-α and disease activity.Accumulation of three or more clinical features during follow-up was significantly associated with high levels of studied cytokines. Triple high positivity was found in 17 patients (20.7%) and correlated with presence of anti-dsDNA antibodies, low levels of C3 component of complement and lupus nephritis. CONCLUSIONS: SLE patients with high serum levels of IL-34, IFN-α and IFN-λ1 more often had lupus nephritis and poor response to immunosuppressive treatment.The triple cytokine elevation was strongly associated with higher disease activity. These results may indicate the need to distinguish this group of patients with such aggressive phenotype and consider targeted multi-therapy.

Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Impact of vitamin D level and supplementation on systemic lupus erythematosus patients during COVID-19 pandemic.

Objectives: In this study, we aimed to assess the impact of serum vitamin D level in systemic lupus erythematosus (SLE) patients with novel coronavirus-2019 (COVID-19) disease on severity of infection, duration of COVID-19 disease course, and fatigue development as a complication of both SLE and COVID-19. Patients and methods: Between April 2020 and January 2021, a total of 38 patients (31 males, 7 females; mean age: 49.2±8.1 years; range, 38 to 65 years) who were previously diagnosed with SLE and on different lines of lupus management were included. The patients presented to chest outpatient clinic and emergency hospital with manifestations suggesting COVID-19 infection. Vitamin D levels were measured in serum by enzymelinked immunosorbent assay (ELISA). Vitamin D supplement was added to treatment protocols for COVID-19. Results: Thirteen (34.2%) patients had normal baseline serum vitamin D levels (≥30 ng/mL), nine (23.7%) patients had vitamin D insufficiency (21 to 29 ng/mL), and 16 (42.1%) patients had vitamin D deficiency (≤20 ng/mL). Low vitamin D levels (insufficiency & deficiency) patients had long SLE disease duration (p=0.06). Also, there was a significant long time spent until recovery from COVID-19 infection in low vitamin D levels (insufficiency & deficiency) patient groups versus those with normal vitamin D (p=0.019). Low baseline vitamin D level patients mainly presented with severe COVID19 symptoms (p=0.04). Patients recovered from COVID-19 had normal vitamin D levels than those who died or were lost to follow-up (p=0.07). After recovery from COVID-19, fatigue was more common in SLE patients with low baseline vitamin D level. Conclusion: Vitamin D seems to play a certain role in the management of COVID-19 infection in SLE patients. Patients with normal vitamin D levels have less severe symptoms, shorter time to recovery, improved COVID-19 outcomes, and less development of fatigue after COVID-19 infection.