Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the stratification of spondyloarthritis from rheumatoid arthritis.

OBJECTIVES: The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). METHOD: Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. CONCLUSION: Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.

The Italian version of the Hand Mobility in Scleroderma (HAMIS) test: evidence for its validity and reliability.

OBJECTIVES: In systemic sclerosis (SSc), hand involvement is frequent and leads to prominent disability. The Hand Mobility in Scleroderma (HAMIS) test is a hand function test for SSc patients assessing the movements included in an ordinary range of motion examination. Our aim is to validate the Italian version of HAMIS, by assessing its test-retest reliability, internal consistency and external consistency in Italian SSc patients. METHODS: The Italian version of HAMIS was administered to 40 SSc patients. HAMIS was translated according to international procedures. Test-retest reliability was assessed by intra-class correlation coefficient (ICC), internal consistency by Cronbach's alpha and external consistency by comparison with Cochin Hand Function Scale (CHFS), fist closure, hand opening, HAQ. RESULTS: HAMIS showed a good testretest reliability (ICCs=0.99 for right and left hand) and internal consistency (Cronbach's α=0.94 for right and 0.93 for left hand) for both hands. A good external consistency was confirmed by the correlation of right and left hand HAMIS with CHFS (p<0.0001, in both cases); fist closure of homolateral hand (p<0.0001 in both cases), opening of homolateral hand (p<0.05 and <0.005, respectively), HAQ (p<0.001 in both cases). HAMIS scores for right and left hands were 7.95±6 .68 and 7.5±6.60 (p=NS), respectively. HAMIS scores for both hands were higher in dSSc and in patients with hand arthritis and flexion contractures. CONCLUSIONS: HAMIS is a hand function test measuring hand disability in SSc. Our results support its validity and reliability in Italian SSc patients.

Early detection of median nerve syndrome at the carpal tunnel with high-resolution 18 MHz ultrasonography in systemic sclerosis patients.

OBJECTIVES: To investigate carpal tunnel syndrome (CTS) with ultrasound (US) in asymptomatic SSc patients and to seek out the relationship between CTS and SSc clinical variables METHODS: In 64 SSc patients (55 women and 9 men, mean age 57±14 years) and in 30 healthy controls, area (MNA), transverse (MNT) and anteroposterior (MNAP) diameters of MN at carpal tunnel were studied with US (My Lab 25 XVG US Esaote 18 MHz). MN flattening ratio (MNFR) was calculated. Duration of disease, subset (limited, diffuse), phase of skin involvement (oedematous, atrophic, fibrotic), modified Rodnan skin score (mRSS) and friction tendon rub were also recorded. RESULTS: MNA (p<0.001), MNT (p<0.005) and MNFR (p<0.005) were significantly higher in the SSc patients than in controls, while no difference in MNAP was found. There was no correlation between median nerve (MN) and SSc clinical features (only lower MNAP correlated inversely with longer disease duration; Spearman coefficient -0.2). CONCLUSIONS: MN involvement is frequently present in all phases of asymptomatic SSc patients, independently to clinical variables.

Juvenile psoriatic arthritis and comorbidities: report of a case associated with enthesitis and celiac disease.

The present authors report the case of a 9-year-old boy affected by psoriasis, juvenile psoriatic arthritis, enthesitis, and celiac disease. The signs and symptoms of the different comorbidities appeared at different times in the clinical history, complicating the overall diagnostic and therapeutic procedures. Cooperation between dermatologists and rheumatologist is mandatory in similar cases, where sophisticated technology and teams with specialized and integrated knowledge are required.

Comparison of the clinical characteristics of vasculitis occurring during anti-tumor necrosis factor treatment or not in rheumatoid arthritis patients. A systematic review of 2707 patients, 18 vasculitis.

OBJECTIVE: Comparison of vasculitis occurring in rheumatoid arthritis (RA) patients undergoing anti-tumor necrosis factor (TNF) treatment and those not. METHODS: Systematic, retrospective, observational study of all RA patients in one center (1997-2004). Vasculitis cumulative incidence in RA patients was calculated in patients receiving anti-TNF or those not. Clinical characteristics of RA and vasculitis were collected. Begaud's imputability tables were used to evaluate the role of anti-TNF in inducing vasculitis. RESULTS: Out of 2707 RA patients, 440 received an anti-TNF. A vasculitis occurred in 6 patients treated with anti-TNF (cumulative incidence: 1.3%), and in 12 patients treated without anti-TNF (cumulative incidence: 0.5%). Characteristics of patients not treated with anti-TNF or treated were respectively (mean): age (years) at vasculitis occurrence: 66.5 vs. 55.3, disease duration (years): 12.2 vs. 13.8, extra-articular features before vasculitis: 16% vs. 60%, number of previous DMARDs: 3.2 vs. 4.5, corticosteroid cumulated dosage (grams): 40.8 vs. 64.3. Vasculitis was cutaneous (58% vs. 67%), neurologic (58% vs. 67%), visceral (8% vs. 17%), and required a treatment in 66% vs. 83%. Using Begaud's tables, anti-TNF could be responsible for inducing vasculitis in 2 out of 6 patients. CONCLUSION: In RA, vasculitis is more frequent during anti-TNF treatment than without anti-TNF. Anti-TNF could be responsible for inducing vasculitis in 2 patients. Patients treated with anti-TNF had more severe RA. It remains to be determined whether vasculitis is a consequence of anti-TNF inefficacy or whether it is treatment-related. In vasculitis occurring with anti-TNF, classical treatment seems more suitable than a switch to another anti-TNF.

Analytical variability in the determination of anti-double-stranded DNA antibodies: the strong need of a better definition of the old and new tests.

Anti-dsDNA antibodies are a heterogeneous group of antibodies, quite specific for SLE. Their variability is related to the assay used, the immunoglobulin class secondary antibody, and the dsDNA source. The standardization of measuring anti-dsDNA antibodies is still poor and different methods yield different results. Several novel technologies were developed during the last decades that represent viable alternatives to the traditional methods such as the chemiluminescent immunoassay (CIA) and multiplex flow immunoassay (MFI). Additionally, positive results for anti-dsDNA antibodies can be detected in patients with inflammatory arthritis (IA) treated with different biologics reducing its clinical specificity for SLE. Anti-dsDNA antibody levels were evaluated in 246 patient samples: 70 SLE and 176 disease control (including 96 IA during treatment with different biologics), using three enzyme immunoassays (indirect enzyme immunoassay, Bio-Rad Laboratories; chemiluminescent immunoassay, Inova Diagnostics; multiplex flow immunoassay, Bio-Rad Laboratories) and three Crithidia luciliae immunofluorescence tests (CLIFT) (Euroimmun AG, Bio-Rad Laboratories, INOVA Diagnostics). Diagnostic performances were assessed both including and excluding the IA patients. Agreements, measured by the Cohen's Kappa between all methods, ranged from moderate to substantial (0.47-0.68). The clinical sensitivities for the anti-dsDNA antibody tests varied from 5.7% by CLIFT A up to 33.3% provided by EIA while the clinical specificities varied from 89.8% by MFI to 98.9% provided by CLIFT B and C. Newer technologies, such as MFI and CIA, showed great potential as a diagnostic application. Significant variations among anti-dsDNA antibody assays were observed confirming the lack of standardization.

Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis.

The variability of demographic, social, genetic, and clinical factors might influence the time between the onset of symptoms and the diagnosis [diagnostic delay (DD)] of ankylosing spondylitis (AS) in different geographic areas. Different clinical manifestations in men and women affected by AS might indicate a possible role of gender in DD. The aim of the present study was to investigate the influence of demographic, social, genetic, and clinical factors on DD and the differences of DD between men and women related to the presence of different demographic, social, clinical, and genetic parameters in an Italian cohort of primary AS patients. A total of 135 Italian primary AS patients (45 female and 90 male, 27.9 ± 0.89 years old at onset) were studied. The DD, gender, education and work (manual or non-manual) levels, and type of first clinical presentation (inflammatory back pain, arthritis, enthesitis) at onset, family history of AS, and HLA B27 presence were analyzed. The DD (8.744 mean ±0.6869) was significantly higher in men (p = 0.0023), in axial presentation (p = 0.0021), and in manual work (even if with low significance, p = 0.047). The lower DD in women in comparison to that in men was likely related to higher education (p = 0.0045) and work (p = 0.0186) levels, peripheral involvement (p = 0.0009), and HLA B27 positivity (p = 0.0231). DD was higher in AS patients: male, employed in manual jobs, and with axial symptoms at onset. In men, DD seemed to be negatively influenced by lower level of education and work, axial clinical presentation, and HLA B27.

The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn).

OBJECTIVES: To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil). METHODS: Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.9%). RESULTS: In SSc su-PAR basal levels were higher than controls (7.48 +/- 2.5 vs 4.69 +/- 0.4 ng/ml; p = 0.001) and were significantly reduced by Alprostadil (5.93 +/- 1.7; p = 0.002), but remain higher than controls (p = 0.03). u-PA basal levels were higher than controls (3.78 +/- 1.5 vs 1.29 +/- 0.3 ng/ml; p < 0.001) and were reduced by Alprostadil (2.39 +/- 1.7; p < 0.001) to control levels. SSc PAI-1 basal levels were lower than controls (31.60 +/- 7.7 vs 48.30 +/- 6.8 ng/ml; p < 0.001) and increased by Alprostadil (34.66 +/- 5.4; p = 0.04), but lower than controls (p < 0.001). SSc t-PA basal levels were higher in respect to controls (1645.81 +/- 792.7 vs 571.95 +/- 75.5 pg/ml; p < 0.0001) and reduced by Alprostadil (1318.06 +/- 603.5; p = 0.04), but still higher than controls (p = 0.001). CONCLUSION: Fibrinolysis were increased in SSc. Infusions of Alprostadil modulate u-PA, su-PAR, PAI-1 and t-PA, restoring near normal levels. In SSc, fibrinolysis system may become a potential target for new therapies.

Sonographic evaluation of the temporomandibular joints in juvenile idiopathic arthritis().

INTRODUCTION: Juvenile idiopathic arthritis (JIA) may cause damage to the temporomandibular joint (TMJ). In oligoarticular forms of JIA, TMJ involvement is often asymptomatic and consequently overlooked. The aim of this study was to evaluate the presence of TMJ joint effusion (JE) by ultrasonography (US) in patients with early arthritis. MATERIALS AND METHODS: We examined 68 children (57 girls, 11 boys, age range 9.1-16.0 years, mean age 11.0 years) recently diagnosed with JIA. None had received any specific treatment for inflammation. Symptomatic TMJ involvement was diagnosed when one or more of the following were present: 1) recurrent pain (spontaneous or on movement of the jaw); 2) crepitation; 3) feeling of stiffness or fatigue of the jaw; 4) intermittent locking. US of the TMJ was performed in static and dynamic phases with a General Electric LOGIQ7 scanner and a linear transducer (8.5 MHz) positioned along the axis of the mandibular ramus. JE was diagnosed when the joint capsule was ≥1.5 mm thick. RESULTS: Forty-six out (68%) of 68 children had US evidence of TMJ effusions (bilateral in 16 [35%] cases), but only 2/46 were symptomatic. CONCLUSIONS: These data suggest that children with early stage oligoarticular JIA children are likely to have inflammation of the TMJs even in the absence of symptoms. US is a simple-to-use, noninvasive, radiation-free tool that can provide useful information in the assessment and follow-up of TMJ involvement in children and young adults with JIA.