Anticitrullinated protein/peptide antibodies and rheumatoid factors: two distinct autoantibody systems

In a previous issue of Arthritis Research and Therapy, Ursum and colleagues report the relative stabilities of anticitrullinated protein/peptide antibodies (ACPAs) and IgM rheumatoid factors during the course of rheumatoid arthritis and their differential correlation with markers of the acute-phase response. These findings add to a growing body of evidence highlighting the distinct nature of these two autoantibody systems and the role of ACPAs as a disease-specific marker of rheumatoid arthritis

The clearance of apoptotic cells: Implications for autoimmunity

Apoptosis has been clearly characterised by the ability to limit the activation of inflammatory responses through the disposal of the apoptotic cell by rapid uptake by phagocytes. The exposure of phosphatidylserine deriving from the loss of plasma lipid asymmetry is the early membrane signal which alerts the phagocyte about the imminent apoptotic death of the cell. Also modifications of membrane carbohydrate groups on apoptotic cells contribute to phagocyte recognition. Soluble proteins such as C1q, mannose-binding lectin, surfactant proteins A and D, C-reactive protein, C3bi, β2-glycoprotein I and growth arrest specific gene-6 bind to apoptotic cells and act as 'opsonins' thus favouring their clearance. A redundant and promiscuous system of receptors including integrins, scavenger receptors, CR3 and CR4, calreticulin, CD14 and Mer receptor ensures an efficient and rapid uptake of apoptotic cells. In animal models and in human pathology, single genetic defects of molecules involved in apoptotic cell clearance seem to be the main determinant in the development of autoimmunity. The uptake of apoptotic cells by phagocytes provides an immunomodulatory effect in that it triggers the release of anti-inflammatory cytokines, inhibits the production of inflammatory cytokines and leads to T cell tolerance. Impaired clearance of apoptotic cells or the presence of 'danger' signals may modify the balance between tolerance induction and activation of T cells leading to an effective autoimmune response. © 2002 Elsevier Science B.V. All rights reserved

B cells in SLE. Different biological drugs for different pathogenic mechanisms

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by a complex multi-factorial pathogenesis and a great clinical polymorphism. SLE is considered to be a B cell disease in which autoantibodies are the major players. Recently, the central role of B cells has been confirmed and it has been shown that that the relative frequency of B cells subsets is altered in SLE patients. Conventional immunosuppressive therapies such as azathioprine, cyclophosphamide or methotrexate, reduce disease activity and improves the patient's general health conditions. These treatments have possible side effects; in fact they could compromise liver function, fertility and innate and adaptive immune responses. Moreover, for unknown reasons a small group of SLE patients is refractory to immunosuppressive therapy. In these cases finding an effective treatment becomes a challenge. The progress in therapeutic antibody technology has led to the production of a wide array of humanized monoclonal antibodies, targeting specific cell types or pathways, initiating a new era in the treatment of autoimmune disorders. In contrast to general immuno-suppression, the availability of drugs interfering with specific pathogenetic pathways gives the possibility to choose therapies tailored to each disease in each patient. © 2007 Elsevier B.V. All rights reserved

Sleep quality in patients with primary Sjögren's syndrome

Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables.Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables

In ricordo di Antonio Zoppini

Il Prof. Antonio Zoppini è venuto a mancare nell’estate di quest’anno, dopo una lunga e dolorosa malattia. Il triste evento è stato vissuto in forma strettamente privata, ma è giusto ricordare il Prof. Zoppini a tutti coloro che Lo hanno conosciuto ed apprezzato all’interno del mondo accademico e ancor più ampiamente in ambito professionale, nell’arco della sua lunga carriera...

[Are there differences among anti-TNFα biological drugs?].

Objective: To provide an analysis and a guide tool in using TNFa-antagonists in the current clinical practice. Methods: Review of the literature on the differences among the three TNFa-antagonists in terms of molecular structure, mechanism of action, pharmacokinetics, effects on the immune and neuroendocrine systems, and therapeutic indications. Results and conclusions: Unfortunately, results of direct comparison studies are lacking. One could obviate this problem by performing statistical-mathematical extrapolations, but there are very few and very small-sized published experimental evidences

Microchimerism in Sjögren's syndrome.

[No abstract available

Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that can be considered as a prothrombotic state1. A great number of studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of this disease. The presence of large amounts of superoxide radicals and hydrogen peroxide produced by activated neutrophils has been reported in the synovial fluid of patients with RA. This may cause lipid peroxidation that yields a wide variety of end products, including malondialdehyde (MDA), a known marker of oxidative stress. These products are therefore transported from the synovial fluid to the blood circulation system2. Considering that elevated levels of MDA have been observed in the blood plasma of patients with RA2, the aim of this pilot study was to investigate whether the elevated levels of plasmatic MDA could be associated with a modification of the total antioxidant capacity (TAC) of blood plasma that is usually indicative of a “systemic” oxidative imbalance3. In addition, in view of their activity as redox effectors or scavengers4, as well as determinants of thrombus formation5, we evaluated red blood cell (RBC) features in terms of their redox state and lifespan marker molecules