The association between duration of remission, fatigue, depression and health-related quality of life in Italian patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the impact of duration of remission on the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE). METHODS: We conducted a 5-year retrospective study on two Italian cohorts. Remission was defined as a continuative period of no clinical disease activity, according to the Systemic Lupus Erythematosus Disease Activity Index 2 K, and a permitted maximum prednisone dose of 5 mg/day. HRQoL was measured using the 36-Item Short-Form Health Survey (SF36) during the last visit. RESULTS: We enrolled 136 female SLE patients. During observation, 15 (11%) patients had been in remission for ≥1 and <2 years, 15 (11%) for ≥2 and <3 years, 19 (14%) for ≥3 and <4 years, 9 (7%) for ≥4 and <5 years, and 53 (39%) had been in prolonged remission for ≥5 years. In the multivariate model, considering depression and fatigue as covariates, patients in prolonged remission showed significantly better scores in the physical functioning (p = 0.039), role physical (p = 0.029), bodily pain (p = 0.0057), general health (p = 0.0033) and social functioning (p = 0.0085) components of the SF36, compared with those in remission <5 years or unremitted. Subsequent mediation analyses found that these effects were partly influenced by depression. CONCLUSION: Lupus remission could improve the HRQoL of SLE patients, particularly when associated with appropriate management of depression and fatigue.

Anti-D4GDI antibodies activate platelets in vitro: a possible link with thrombocytopenia in primary antiphospholipid syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 αIIbß3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients. CONCLUSIONS: 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.

Is fatigue a cause of work disability in systemic lupus erythematosus? Results from a systematic literature review.

OBJECTIVE: Fatigue affects the almost totality of Systemic Lupus Erythematous (SLE) patients impairing physical function and leading to a strong reduction of health-related quality of life (HRQoL). Similarly, SLE patients have an increased rate of work loss and work limitations. The aim of our paper was to systematically assess the relationship between fatigue and work disability in SLE. MATERIALS AND METHODS: We performed a systematic review using the terms "fatigue" and "employment", "work disability", "work impairment", "presenteeism" and "absenteeism." RESULTS: 19 studies were identified. Fatigue was involved in the development of work loss. In employed patients, fatigue led to impairment of work productivity and presenteeism with a parallel increase of both direct and indirect health costs. Fatigue also affected parenting and household productivity. CONCLUSIONS: An adequate control of fatigue could improve physical and work performance in SLE patients thus reducing rates of work loss.

Inflammation as a mediator of the association between osteoporosis and hearing loss in older subjects: a population-based study.

OBJECTIVE: Due to the aging of populations, the prevalence of hearing loss and osteoporosis is increasing. Previous studies have found an association between these conditions. Nevertheless, the pathophysiologic pathway of such an association has not yet been established. The present study aimed at evaluating the association, if any, of hearing loss with osteoporosis in an older unselected population, and whether this association varied according to inflammatory status. PATIENTS AND METHODS: We assessed the association of osteoporosis with a self-reported hearing loss in all 310 subjects aged 75+ living in Tuscania (Italy), without exclusion criteria. Bone density was assessed by calcaneal quantitative ultrasound; osteoporosis was defined as a T-score ≤ -2.5 Standard Deviation. RESULTS: Hearing loss was associated with osteoporosis (OR = 1.84, 95% CI = 1.03-3.28; p = 0.40) in multivariable logistic regression analysis, after adjusting for potential confounders. Analysis of the interaction term indicated that this association varied according to the erythrocyte sedimentation rate, ERS (p = 0.030), and high-sensitivity C reactive protein, hs-CRP (p = 0.017) but not sex (p = 0.832). Of notice, this association was significant only for higher levels of inflammatory parameters (OR = 2.82; 95% CI = 1.15-6.90; p = 0.023 for the higher ERS tertile; and OR = 3.81; 95% CI = 1.36-10.63; p = 0.011 for the higher hs-CRP tertile vs. lower tertiles). CONCLUSIONS: Hearing loss is associated with osteoporosis in community dwelling elderly. Such an association seems to depend upon higher inflammation levels.

The IL33/ST2 axis in Sjogren syndrome in relation to disease activity.

OBJECTIVE: Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disorder characterized by infiltration of the exocrine glands leading to secretory insufficiency. Despite the progress made in understanding the pathogenesis of the SS, many aspects remain to be clarified. Interleukin-33 (IL33) is a recently discovered cytokine, belonging to IL-1 superfamily. IL33 and its soluble receptor ST2 were implied in a number of immune and in autoimmune diseases pathogenesis. In this work ,we analyzed expression of IL33 and ST2 in Sjogren's syndrome. PATIENTS AND METHODS: Serum IL-33 and soluble ST2 were analyzed using commercial ELISA kit in 15 pSS, 9 patients with Systemic Lupus Erythematosus and 9 controls. RESULTS: We found significant hyperexpression of sST2 in sera of SS patients and SLE patients compared to healthy subjects (p = 0.04 and p = 0.07, respectively). In pSS, sST2 levels in pSS positively correlated with activity index SSDAI (r = 0.662, p = 0.007). In SLE, we found positive correlation between ST2 and SLEDAI 2K (r = 0.685, p = 0.04). Circulating levels of IL-33 were detectable in 2 of 15 SS patients, in 2 SLE patients and in 1 of control subjects. CONCLUSIONS: We found an hyperexpression of sST2 in pSS and SLE patients with a possible immune modulatory role, because of a substantial suppression of circulating IL33. In our pSS and SLE cohort, sST2 levels were in correlation with disease activity indices.

Subclinical carotid atherosclerosis in elderly patients with primary Sjögren syndrome: a duplex Doppler sonographic study.

A growing body of evidence presents a link between chronic inflammatory rheumatic diseases and atherosclerosis. To evaluate subclinical carotid atherosclerosis in an elderly group of patients with primary Sjögren syndrome compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors, we enrolled 18 patients with Primary Sjögren Syndrome (mean age 65 ± 5.93 SD) and 18 mild Ostheoarthritic patients (mean age 66 ± 5.94 SD) from the outpatient department of Rheumatology, University “Campus Bio-Medico, Rome, Italy, matched for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler sonographic study of carotids was performed in order to evaluate intima-media thickness (IMT), stiffness and haemodynamic parameters [resistivity and pulsatility indices (RI and PI, respectively)]. No significant difference was found between primary Sjögren syndrome and control patients in IMT, stiffness and haemodynamic parameters. The lack of significant difference in subclinical atherosclerosis between elderly primary Sjögren syndrome and control matched patients, indicates that traditional cardiovascular risk factors, immunologic alterations and chronic inflammation do not influence the progression of vascular damage in the carotid circulation of patients with median disease duration of 6.5 years.