Laura Muntean

BACKGROUND: Osteopontin (OPN) has been implicated in bone remodeling by activating the resorption process. We aimed to study the relationship between OPN, bone mineral density (BMD), bone turnover markers, vitamin D, and osteoporotic vertebral fractures in postmenopausal women. MATERIALS AND METHODS: Serum levels of OPN, osteocalcin, collagen type 1 cross-linked C-telopeptide (CTX), bone alkaline phosphatase, and vitamin D were assessed in 214 postmenopausal women. Bone mineral density was assessed by dual-energy x-ray absorptiometry in lumbar spine and femoral neck, and osteoporotic vertebral fractures by radiographs. RESULTS: Osteopontin levels were significantly higher in osteoporosis group versus osteopenic and normal group (all P < 0.05). The cutoff values of OPN for osteoporosis diagnosis were of 9.47 μg/L at the lumbar spine (area under the curve, 0.67; 95% confidence interval, 0.58-0.75; P < 0.001) and 10.15 μg/L at the femoral neck (area under the curve, 0.69; 95% confidence interval, 0.624-0.77; P = 0.0001), respectively. Postmenopausal women with osteoporosis-related vertebral fractures had significantly higher levels of OPN than those without vertebral fractures (15.69 ± 13.26 vs 12.63 ± 12.46 μg/L; P = 0.02). Significant negative correlations were found between OPN and BMD, which persisted after the adjustment for age at the lumbar spine. Osteopontin levels were directly correlated with bone turnover markers (osteocalcin, bone alkaline phosphatase, and CTX). No significant correlation was found between OPN and vitamin D. Multiple regression analysis showed that age, waist circumference, and CTX were independent predictors of serum OPN levels. CONCLUSIONS: High levels of OPN in postmenopausal women are associated with low BMD, increased levels of bone turnover markers, and osteoporotic vertebral fractures. These findings suggest that OPN might play some role in the pathophysiology of postmenopausal osteoporosis and warrant further clinical investigations.

Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.

BACKGROUND: Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset. METHODS: A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively. RESULTS: Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap). CONCLUSIONS: Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.