No abstract

Serum inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), and procalcitonin (PCT), have been used for the diagnosis of foot infections in patients with diabetes. However, little is known about their changes during treatment of patients with foot infections. The aim of this prospective study was to examine the performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. A total of 61 patients (age 63.1 ± 7.0 years, 45 men and 16 women, 7 with type 1 and 54 with type 2 diabetes) with untreated foot infection (34 with soft-tissue infection and 27 with osteomyelitis) were recruited. Diagnosis of osteomyelitis was based on clinical examination and was confirmed by imaging studies (X-ray, scintigraphy, magnetic resonance imaging). Determination of the inflammatory markers was performed at baseline, after 1 week, after 3 weeks, and after 3 months of treatment. At baseline, the values of CRP, ESR, WBC, and PCT were significantly higher in patients with osteomyelitis than in those with soft-tissue infections. The sensitivity and specificity for the diagnosis of osteomyelitis of CRP (cutoff value >14 mg/L) were 0.85 and 0.83, of ESR (cutoff value >67 mm/h) 0.84 and 0.75, of WBC (cutoff value >14 × 10(9)/L) 0.75 and 0.79, and of PCT (cutoff value >0.30 ng/mL) 0.81 and 0.71, respectively. All values declined after initiation of treatment with antibiotics; the WBC, CRP, and PCT values returned to near-normal levels at day 7, whereas the values of ESR remained high until month 3 only in patients with bone infection. From the inflammatory markers, ESR is recommended to be used for the follow-up of patients with osteomyelitis.

Background: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MND) pattern are highly specific for primary biliary cirrhosis (PBC). Aim and subjects: To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight patients with chronic hepatitis C, 23 patients with systemic lupus erythematosus, and 17 healthy subjects were studied as controls. Methods: PBC specific ANA reactivity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2, IgG3, IgG4) specific antisera as revealing reagents. Results: Fourteen of 90 (15.6%) PBC patients had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive. Conclusions: Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

Objective Breg cells, a regulatory cell subset that produces interleukin‐10 (IL‐10), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies. Methods Forty‐five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc‐associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)–associated PF were studied. The phenotypes of immature/transitional Breg cells (CD19+CD24highCD38high) and memory Breg cells (CD19+CD27+CD24high) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL‐10 after B cell activation. In addition, activation of p38 MAPK and STAT‐3 was measured following stimulation of the cells with B cell receptor (BCR) and Toll‐like receptor 9 (TLR‐9). Results Percentages of memory Breg cells were decreased in patients with early SSc (mean ± SEM 1.85 ± 0.38%), those with established SSc (1.6 ± 0.88%), those with SSc‐associated PF (1.52 ± 0.17%), and those with RA‐associated PF (1.58 ± 0.26%), compared to healthy controls (6.3 ± 0.49%; each P < 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL‐10 by Breg cells after stimulation with TLR‐9 was impaired in patients with SSc, particularly those with SSc‐associated PF. Activation of STAT‐3 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR‐9. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc‐associated PF. Conclusion This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT‐3 activation upon stimulation with BCR and TLR‐9. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc.

Anti-Topo I, anti-CENP, and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and anti-NOR90 abs are associated with ILD and/or PAH.