Abstract Recently, a new syndrome, namely the “Autoimmune/inflammatory syndrome induced by adjuvants” (ASIA) has been defined. In this syndrome different conditions characterized by common signs and ...symptoms and induced by the presence of an adjuvant are included. The adjuvant is a substance capable of boosting the immune response and of acting as a trigger in the development of autoimmune diseases. Post-vaccination autoimmune phenomena represent a major issue of ASIA. Indeed, despite vaccines represent a mainstay in the improvement of human health, several of these have been implicated as a potential trigger for autoimmune diseases. Sjogren's Syndrome (SjS) is a systemic chronic autoimmune inflammatory disease characterized by the presence of an inflammatory involvement of exocrine glands accompanied by systemic manifestations. Own to the straight association between infectious agents exposure (mainly viruses) and sicca syndrome development, the possible link between vaccine and SjS is not surprising. Indeed, a few cases of SjS following vaccine delivery have been reported. At the same extent, the induction of SjS following silicone exposure has been described too. Thus, the aim of this review was to focus on SjS and its possible development following vaccine or silicone exposure in order to define another possible facet of the ASIA syndrome.
Ferritin has a key role in Adult-onset Still’s disease (AOSD). Its production seems related to macrophage activation of which sCD163 is a major serum marker. Thus, we aimed at evaluating the role of ...sCD163 in AOSD and its relationship with ferritin. Furthermore, we determined the expression of CD163 and ferritin in a lymph-node from an AOSD patient. sCD163 and serum ferritin were measured in 34 patients with AOSD (21 active, 13 non-active), 18 sepsis and 22 healthy controls (HC). Immunohistology was performed on a lymph-node from an AOSD patient in order to detect CD163 and ferritin. A tonsil from an HC was used as control. Mean sCD163 (8.6 ± 5.4 mg/L) was higher in active AOSD than “non-active” patients (4.6 ± 2.7 mg/L,
p
= 0.02). The mean sCD163 in AOSD (6.9 ± 4.9 mg/L) and sepsis (7.1 ± 5.6 mg/L) were higher than in HC (2.56 ± 1.17 mg/L,
p
< 0.001), but no difference between AOSD and sepsis was detected. sCD163 positively correlated with ferritin (
p
= 0.0045;
r
= 0.4755) only in AOSD. Serum ferritin (mean 3,640.1 ± 6,896.9 µg/L) was higher in active AOSD than in sepsis (1,720.2 ± 3,882.1 µg/L,
p
< 0.007). CD163 was equally distributed in the B and T areas of both lymph-node and tonsil. Differently from the tonsil, ferritin was expressed only in the lymph-node B area. sCD163 is a marker of disease activity in AOSD. The correlation with ferritin may lead to hypothesize a macrophage activation related to hyperferritinemia. Ferritin was found expressed only in the B area of the AOSD lymph-node, suggesting a role for this molecule as an antigen in the disease pathogenesis.
Objective
The objective of this report is to investigate the prognostic value of minor salivary glands (MSG) assessment, routinely performed with hematoxilin-eosin (H&E) staining, for the diagnosis ...of primary Sjögren’s syndrome (pSS).
Methods
We retrospectively evaluated clinical, serological and histological features of 794 pSS patients. H&E-stained sections were assessed using the Chisholm and Mason grading system and/or the focus score (FS).
Results
FS allowed the identification of a number of differences in the disease spectrum, and its prognostic role was further confirmed by quantifying the association between FS value and clinical/serological variables with binary logistic regression. Moreover, hypocomplementemia and FS resulted the only variables associated with lymphoma at univariate analysis, and FS appeared to be associated with lymphoma independently on complement fraction concentrations. Conversely, when patients were divided according to the Chisholm and Mason grading system, we failed to observe any significant difference between subgroups.
Conclusion
In addition to its diagnostic role, our data seem to support that the routine assessment of MSG-FS with H&E staining is useful to predict at the time of diagnosis the adverse outcomes, such as lymphoma and extraglandular manifestations, that complicate the pSS course. On this basis, it should be recommended that an MSG biopsy be performed even in those patients displaying clinical and serological criteria, allowing the diagnosis of pSS independent of histological status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis. Methods: 48 wrists of 24 ...patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician’s global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists. Results: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman’s r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination. Conclusion: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.
Summary
Evidence exists that interleukin (IL)‐10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved ...in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL‐20, IL‐24 and IL‐19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL‐20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL‐24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL‐19 serum levels were higher in HC and OA compared with PsA and RA patients; IL‐19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL‐19 serum levels after biological treatment. Therefore, IL‐19 seems to be involved mainly in the joint inflammation, whereas IL‐20 and IL‐24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.
Summary
Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as ...supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real‐time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non‐remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.
‐Significant correlation between P. gingivalis rate in total bacteria genomes and disease activity in terms of DAS28 values and remission status.
‐Oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to a more active disease.
‐Beyond citrullination and antibody production, P. gingivalis could be implicated in triggering a pro‐inflammatory state in rheumatoid arthritis.
Musculoskeletal US can be useful in monitoring RA. It can be time-consuming and there is no consensus in defining the joints to evaluate. We assessed the validity, sensitivity to change and ...feasibility of a reduced 6-joint US score in patients with RA starting therapy with an anti-TNF agent.
A group of consecutive RA patients starting etanercept were investigated. The patients underwent clinical evaluation, laboratory tests and US assessment at baseline and 3 months. A semi-quantitative score (0-3) was used to evaluate synovial effusion (SE), synovial proliferation (SP) and power Doppler (PD) signal in 12 joints. A process of data reduction, based on the frequency of synovial site involvement by US-SE, US-SP and US-PD signal, was conducted to investigate the validity of a 6-joint US assessment.
Forty-five RA patients were evaluated. A significant decrease in all clinical, serological and 12-joint US parameters was found at follow-up. A significant correlation between changes in the DAS-28 and changes in the US scores in the 12-joint assessment was observed at follow-up (P < 0.001). A reduced 6-joint US score was obtained, including wrist, second MCP and knee joints of both sides, detecting US-SE in 97.78% of patients, US-SP in 100% of patients and positive US-PD in 100% of patients. The 6-joint US score showed a highly significant correlation with changes in DAS-28 (P < 0.001). The 6-joint evaluation was quick and easy to do.
A 6-joint US assessment may be a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA.
Thrombocytopenia is a manifestation associated with primary antiphospholipid syndrome (PAPS), and many studies have stressed the leading role played by platelets in the pathogenesis of ...antiphospholipid syndrome (APS). Platelets are highly specialized cells, and their activation involves a series of rapid rearrangements of the actin cytoskeleton. Recently, we described the presence of autoantibodies against D4GDI (Rho GDP dissociation inhibitor beta, ARHGDIB) in the serum of a large subset of SLE patients, and we observed that anti-D4GDI antibodies activated the cytoskeleton remodeling of lymphocytes by inhibiting D4GDI and allowing the upregulation of Rho GTPases, such as Rac1. Proteomic and transcriptomic studies indicate that D4GDI is very abundant in platelets, and small GTPases of the RHO family are critical regulators of actin dynamics in platelets.
We enrolled 38 PAPS patients, 15 patients carrying only antiphospholipid antibodies without clinical criteria of APS (aPL carriers) and 20 normal healthy subjects. Sera were stored at - 20 °C to perform an ELISA test to evaluate the presence of anti-D4GDI antibodies. Then, we purified autoantibodies anti-D4GDI from patient sera. These antibodies were used to conduct in vitro studies on platelet activation.
We identified anti-D4GDI antibodies in sera from 18/38 (47%) patients with PAPS, in sera from 2/15(13%) aPL carriers, but in no sera from normal healthy subjects. Our in vitro results showed a significant 30% increase in the activation of integrin αIIbβ3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients.
In conclusion, we show here that antibodies anti-D4GDI are present in the sera of PAPS patients and can prime platelet activation, explaining, at least in part, the pro-thrombotic state and the thrombocytopenia of PAPS patients. These findings may lead to improved diagnosis and treatment of APS.
LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as ...autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(T
)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.
Background
Adhesion molecule CD44 contributes to T cell migration into target organs. A higher expression of CD44v3 and v6 isoforms has been identified on T cells from systemic lupus erythematosus ...(SLE) patients. The aim of this study was to investigate the expression of CD44v3/v6 on T cells of SLE patients in order to evaluate their correlation with clinical features.
Methods
Sixteen healthy subjects (HSs) and 33 SLE female patients were enrolled. Fifteen patients were in remission (Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) = 0) and 18 patients had an active disease (SLEDAI-2K ≥ 4). Experiments were conducted by flow cytometry.
Results
Expression of CD44v3 on CD4+ and CD8+ T cells was higher in active patients compared to HSs (p = 0.0097 and p = 0.0096). CD44v3 on CD8+ T cells was also higher in active patients compared to patients in remission (p = 0.038). CD44v6 was higher on CD4+ and CD8+ T cells from active patients compared to HSs (p = 0.003 and p = 0.0036) and to patients in remission (p = 0.01 and p = 0.02). In active patients the ratio CD44v3/v6 was unbalanced towards isoform v6 on both T cell populations. In a receiver operating characteristic curve analysis, CD44v6 on CD4+ T cells was the most sensitive and specific one (specificity of 81.8%, sensitivity of 75%). Expression of CD44v6 on CD4+ and CD8+ T cells correlated with the SLEDAI-2K (p = 0.03, r = 0.38 and p = 0.02, r = 0.39). CD44v6 and CD44v3 on CD8+ T cells associated with nephritis and arthritis (p = 0.047 and p = 0.023).
Conclusions
CD44v3/v6 can be used as biomarkers of disease activity and phenotypes; isoform v6 on CD4+ T cells can be useful as a diagnostic biomarker.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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