Interleukin-13 (IL-13)in autoimmune rheumatic diseases: relationship with autoantibody profile

Objective: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL- 13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. Methods: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n = 114), SS (n = 52) and Scl (n =32). Results: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serian levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL- 13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients,without RE SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinical features of each disease. Conclusion: The evidence of higher IL- 13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However the different autoantibody synthesis by Bcells recognises different pathways depending on the underlying autoimmune disease

The role of Interleukin-12 in immune-mediated rheumatic diseases

Objective: IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL-12 in rheumatic diseases is not clear. Aim of the study was to determine IL-12 serum levels in immune rheumatic diseases and to analyse the relationship of this cytokine with main clinical and laboratory parameters. Methods: we analysed, by ELISA, serum IL-12 levels in 114 patients with SLE, 47 with SS, 32 with SSc, 84 with RA, 138 with PA and in 17 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. Results: IL-12 serum levels were significantly higher in SLE and SS patients respect to controls. IL-12 serum levels were significantly higher in SLE patients compared to those affected by RA, PA and SSc. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects with fever or in those without renal involvement, while no correlation was found in the other rheumatic immune diseases. Conclusions: these findings suggest that IL-12, modulating cell and humoral immune responses, is involved in the pathogenesis of immune rheumatic diseases, such as SLE and SS

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of &gt; 6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; pCombining double low line0.68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; pCombining double low line0.14), and a higher resolution of pain was observed (35 % vs. 14 %; pCombining double low line0.22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed

Direct use of eazyplex\uae SuperBug CRE assay from positive blood cultures in conjunction with inpatient infectious disease consulting for timely appropriate antimicrobial therapy in Escherichia coli and Klebsiella pneumoniae bloodstream infections

Objectives: To describe a rapid workflow based on the direct detection of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) producing CTX-M extended-spectrum \u3b2-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy. Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting bla CTX-M, bla KPC, bla NDM, bla OXA-48-like, and bla VIM genes by the eazyplex\uae SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting. Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored bla CTX-M and/or bla KPC and/or bla VIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers. Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organism

Ultrasound measurements at the proximal phalanges in male patients with psoriatic arthritis

Bone ultrasound parameters at the proximal phalanges of the hands were measured in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic involvement and 16 with axial involvement), comparing the findings with those in 16 rheumatoid arthritis (PA) patients, 20 ankylosing spondylitis (AS) patients and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were significantly lower in RA (p <0.001 andp <1 x 10(-5)) and PA (p <0.03 and p <1 x 10(-6)) patients than in controls, while there was no statistically significant difference between AS patients and healthy subjects. Ultrasound parameters showed a significant negative correlation with age in all groups. in each patient group ultrasound values were unrelated either to disease duration or to inflammatory indices such as erythrocyte sedimentation rate and C-reactive protein. Moreover no significant differences were observed between ultra-sound parameters of the dominant and the nondominant hand. PA patients with and without axial radiologic changes did not show any differences in ultrasound parameters. However, PA subjects with peripheral involvement only had significantly higher Ad-SoS (p <0,04) and UBPS (p <0.04) values than RA patients. PA patients with axial lesions had significantly lower (p <0.04 and p <0.01) ultrasound values than AS patients. These findings suggest that PA uItrasound techniques performed at the peripheral revel are of value to speculate on bone involvement, although we think that ultrasound measurements cannot yet be recommended for monitoring bone involvement in these patients

Interleukin-13 in autoimmune rheumatic diseases: Relationship with the autoantibody profile

Objective: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL- 13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. Methods: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n = 114), SS (n = 52) and Scl (n =32). Results: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serian levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL- 13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients,without RE SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinical features of each disease. Conclusion: The evidence of higher IL- 13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However the different autoantibody synthesis by Bcells recognises different pathways depending on the underlying autoimmune disease

Comparison of the health assessment questionnaire and arthritis impact measurement scale in patients with psoriatic arthritis

Objective. To determine which of two instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS), was more closely correlated with the main parameters reflecting activity and severity of psoriatic arthritis. Methods. Both instruments were administered to 72 consecutive patients with psoriatic arthritis. Results. Global HAQ and AIMS scores,were closely correlated with each other (r(s) =0.747; P<0.00001). AIMS physical function scales namely physical activity, dexterity, social activity and activities of daily living - were moderately or closely correlated with the main clinical disease activity parameters, most notably morning stiffness of axial joints (r(s)= 0.271-0.551). Scales measuring psychological status yielded weaker correlations with disease activity parameters (r(s)= 0.241-0.277) and were also correlated with the visual analog scale score for skin lesion severity. Morning stiffness of peripheral joints was correlated only with two AIMS scales, namely pain (r(s)= 0.532) and activities of daily living (r(s)= 0.303). Severity of radiological damage of peripheral and axial joints was most closely correlated with the scales of physical function, most notably physical activity. The global and scale HAQ scores showed moderate to close correlations with the main clinical disease activity parameters, most notably morning stiffness of axial joints. The global HAQ score was also correlated with radiological carpal involvement and with the radiological severity of peripheral joint involvement, whereas only the arising and hygiene scales were (moderately) correlated with the radiological severity of spinal involvement. Conclusion. Although both the HAQ and the AIMS were useful in assessing health status in psoriatic arthritis patients, only the AIMS captured some of the effects of the skin lesions. Our data also suggest that the AIMS may be more effective than the HAQ for evaluating the effect of radiological lesions produced by psoriatic arthritis

Interleukin-13 in synovial fluid and serum of psoriatic arthritis

Synovial fluid (8F) and serum IL13 levels were determined in 35 patients with psoriatic arthritis (PsA), 36 with RA, and 15 with OA. The main clinical and laboratory variables, including number of painful and/or swollen joints, Ritchie index, morning stiffness, erythrocyte sedimentation rate, level of C reactive protein, level of rheumatoid factor, and SF analysis, were also evaluated. Results: SF IL13 levels were significantly higher in patients with PsA (p<0.02) or RA (p<0.012) than in patients with OA, with no significant difference between the former two. SF IL12 levels were significantly higher in patients with PsA (p<0.023) than in those with OA. Serum IL13 (p<0.0001) and IL12 (p<0.02) levels were lower in patients with PsA than in those affected by RA. Only patients with PsA had higher IL13 levels in SF than in serum (p<0.002). The IL13 SF/serum ratio was higher in the PsA group than in the group with RA (p<0.005) or OA (p<0.026). SF IL13 levels correlated with serum IL13 levels (p<0.0001) in RA and with SF IL12 levels (p<0.03) in PsA. Conclusions: In PsA, there appears to be localised production of IL13, in balance with IL12, in the inflamed joints. The distinct IL13 secretion profiles in PsA, RA, and OA may be related to the clinical pictures, reflecting the different pathogenic mechanisms involved in inflammatory and degenerative joint disease

Class specific rheumatoid factors and antiphospholipid syndrome in systemic lupus erythematosus

The relationship of rheumatoid factors (RF) with antiphospholipid syndrome (aPLS) and anticardiolipin antibodies (aCL) has rarely been investigated in systemic lupus erythematosus (SLE). We found IgM-RF, IgG-RF, IgA-RF, IgM-aCL, IgG-aCL, IgA-aCL, respectively, in 35.4%,, 35.4%, 33.8%, 23.1%, 23.1%, 20.0% of 65 SLE patients. Class specific RFs were negatively associated (P < 0.05) with IgG-aCL. The frequency of definite: or probable aPLS according to Alarcon-Segovia classification criteria was significantly (P < 0.05) different (8.7% vs 30.9%) in patients with or without IgG-RF. Among the other clinical features of SLE. we found that patients with IgG-RF, compared to patients lacking this autoantibody, showed a lower frequency (P < 0.05) of serositis (21.7% vs 52.4%) and hematologic (52.2% vs 80.9%) disorders. The levels of IgG-RF and IgM-RF negatively correlated with the number of ARA criteria (P < 0.05) but not with the indices of diseases activity or damage. Our study shows that in SLE the presence of RFs are not markers of severity of the disease, but the negative association between IgG-RF and IgG-aCL suggests a distinct role of these autoantibodies in the pathology of SLE, whereas the presence of IgG isotype may identify a subset of SLE patients having a lower risk to develop some clinical manifestations such as aPLS