Marta Vadacca

Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies.

The authors assessed the prevalence of neuropsychiatric manifestations occurring in patients with systemic lupus erythematosus (NPSLE), according to the American College of Rheumatology standardized definitions for NPSLE, and evaluated the relationship between NPSLE and antiphospholipid antibodies. Sixty-one consecutive SLE patients were studied. Neuropsychiatric manifestations consistent with the diagnosis of NPSLE occurred in 44 (72%). Patients with NPSLE showed significantly higher levels of anticardiolipin antibodies.

Adipokines and Systemic Lupus Erythematosus : Relationship with Metabolic Syndrome and Cardiovascular Disease Risk Factors

Objective. To study concentrations of adipokines in patients with systemic lupus erythematosus (SLE) and the relationship among adipokines, the metabolic syndrome (MeS), and cardiovascular disease (CVD) risk factors. Methods. We enrolled 50 SLE patients and 26 controls, all women. Leptin, resistin, visfatin, and adiponectin were measured by commercial ELISA kits. Results. MeS prevalence was increased among subjects with SLE. Leptin levels were higher in patients with SLE than controls. Among SLE patients, independent determinants of leptin were insulin levels (p < 0.0001), triglycerides (p = 0.03), body mass index (p = 0.02), corticosteroid dosage (p = 0.02), and SLE Disease Activity Index (p = 0.005). Other adipokines did not differ between SLE patients and controls. Conclusion. Leptin was increased in SLE patients and could play a role in SLE-related cardiovascular diseases.

Leptin in immuno-rheumatological diseases

Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders.

Antibodies to anionic phospholipids and anti-β2-GPI: association with thrombosis and thrombocytopenia in systemic lupus erythematosus

In this study, we evaluated the prevalence and association with thrombosis and/or thrombocytopenia of IgG and IgM antibodies to cardiolipin (aCL), phosphatidic acid (aPA), phosphatidylinositol (aPI), phosphatidylserine, and beta(2)-glycoprotein I (abeta(2)-GPI) in systemic lupus erythematosus (SLE). Sera were obtained from 87 patients affected by SLE (77 of the 87 patients were females), 41 of them with a history of arterial and/or venous thrombosis. Antiphospholipid antibodies and abeta(2)-GPI were evaluated by enzyme-linked immunosorbent assay. IgG-aCL, IgG-aPA, IgG-aPI, IgG-aPS, and IgG-abeta(2)-GPI were found in 53%, 37%, 32%, 38%, and 24% of patients, respectively. IgM-aCL, IgM-aPA, IgM-aPI, IgM-aPS, and IgM-abeta(2)-GPI were detected in 15%, 17%, 18%, 14%, and 16%, respectively. With respect to antibody titer, IgG-aCL strongly correlated with all other antiphospholipid antibodies and abeta(2)-GPI of IgG isotype. Thrombosis was significantly associated with IgG-aPA (p = 0.044), IgG-aPI (p = 0.038), IgG-aPS (p = 0.026), IgG-abeta(2)-GPI, IgM-aPA (p = 0.044), IgM-aPI (p = 0.024), and IgM-aPS (p = 0.01), irrespective of antibody titer, whereas IgG-aCL were associated with thrombosis and thrombocytopenia when taken at medium-high titer (p = 0.009 and p = 0.046, respectively). Our results confirm that, besides aCL and abeta(2)-GPI, other antibodies to negatively-charged phospholipids are present in a large percentage of patients with SLE. However, it remains doubtful whether these other antiphospolipid antibodies actually represent an important parameter predictive of thrombosis and thrombocytopenia in SLE.

Anti-lactoferrin antibodies in systemic lupus erythematosus : isotypes and clinical correlates

Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity (p=0.017), anti-dsDNA (0.04), and anticardiolipin antibodies (p=0.02) and were associated with Raynaud’s phenomenon (p=0.028), renal involvement (p=0.007), serositis (p=0.026), and history of thrombosis (p=0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role.

Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis.

The lungs are frequently involved in Connective Tissue Diseases (CTDs). Interstitial lung disease (ILD) is one of the most common pleuropulmonary manifestations that affects prognosis significantly. In practice, rheumatologists and other physicians tend to underestimate the impact of CTD-ILDs and diagnose respiratory impairment when it has reached an irreversible fibrotic stage. Early investigation, through clinical evidence, imaging and - in certain cases - lung biopsy, is therefore warranted in order to detect a possible ILD at a reversible initial inflammatory stage. In this review, we focus on lung injury during CTDs, with particular attention to ILDs, and examine their prevalence, clinical manifestations and histological patterns, as well as therapeutic approaches and known complications till date. Although several therapeutic agents have been approved, the best treatment is still not certain and additional trials are required, which demand more knowledge of pulmonary involvement in CTDs. Our central aim is therefore to document the impact that lung damage has on CTDs. We will mainly focus on Rheumatoid Arthritis (RA), which - unlike other rheumatic disorders - resembles Idiopathic Pulmonary Fibrosis (IPF) in numerous aspects.

The unusual association of three autoimmune diseases in a patient with Noonan syndrome

We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously reported. Should the occurrence of autoimmune disorders in NS be confirmed, a relevant clinical and laboratory evaluation of NS patients should be performed in order to clarify whether the immune system involvement represents only an occasional event or is a feature of the disease.

Raynaud’s phenomenon and antiphospholipid antibodies in systemic lupus erythematosus: is there an association?

Objective: To evaluate the association of IgG and IgM antibodies directed against different negatively charged phospholipids (that is, anticardiolipin (aCL), antiphosphatidylinositol, antiphosphatidylserine, and antiphosphatidic acid) and anti-β2-glycoprotein I (aβ2GPI), with Raynaud’s phenomenon in patients with systemic lupus erythematosus (SLE). Methods: Ninety three patients with SLE (81 female), 40 with and 53 without Raynaud’s phenomenon, were included in the study. IgG and IgM antiphospholipid antibodies and aβ2GPI were determined by enzyme linked immunosorbent assay (ELISA). Results: Fifty patients (54%) were positive for IgG and/or IgM antibodies to one or more phospholipid antigens or to β2GPI. The prevalence of all autoantibodies evaluated, either IgG or IgM, was higher in patients without than in those with Raynaud’s phenomenon. A negative association was found between IgG aCL and Raynaud’s phenomenon (p=0.038), whereas autoantibodies other than aCL were not significantly associated with Raynaud’s phenomenon. Conclusion: Our results demonstrate no positive association between antiphospholipid antibodies and Raynaud’s phenomenon in SLE and indicate that measurement of anti-negatively charged phospholipid antibodies other than aCL is not useful as a serological marker predictive for Raynaud’s phenomenon.

Auditory pathway in rheumatoid arthritis. A comparative study and surgical perspectives

Conclusion. Rheumatoid arthritis (RA) patients present with both conductive and sensorineural deafness. Objective. To evaluate the prevalence and features of hearing impairment in patients with RA. Material and methods. A total of 28 RA patients underwent a rheumatological evaluation, including determination of rheumatoid factor, protein 2-glycoprotein I level and the Lee index. An audiological assessment consisting of pure-tone audiometry (PTA) and determination of auditory brainstem responses (ABRs) and transient evoked otoacoustic emissions (TEOAEs) was performed. The results were compared with those of 28 age- and sex-matched healthy subjects. Four selected RA patients underwent stapedectomy; PTA and TEOAEs were evaluated 6 months postoperatively. Results. Increased air conduction thresholds at 250, 500 and 1000 Hz were found in RA subjects in comparison to controls (p<0.001). RA patients showed higher air–bone gaps in PTA (p<0.05) and an increased Wave I latency in ABRs (p=0.03). Decreased reproducibility (p<0.001) and amplitude (p<0.001) of TEOAEs were found in RA subjects in comparison to controls. A significant correlation between disease duration and echo amplitude was noticed (r=0.389). After stapedectomy, a reduction in the air–bone conduction gap (11 vs 2 dB HL) was noticed; no significant difference in TEOAEs was found.

The 677C → T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in epileptic patients affected by systemic lupus erythematosus

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is considered as one of the major manifestations of the disease. Epilepsy has been documented in about 10% of patients with systemic lupus erythematosus (SLE). It is well known that vascular damage in SLE occurs because of multiple mechanisms including hypercoagulation. It has been recently reported that in SLE patients raised levels of homocysteine are associated with arterial thrombosis. Hyperhomocysteinaemia is a condition due to both genetic and non-genetic factors. The most common genetic defect in homocysteine metabolism is a decreased activity of a common 5,10-methylenetetrahydrofolate reductase (MTHFR) variant (677C -->T, a thermolabile form). In this paper we describe the epileptic manifestations in six out of 55 SLE patients. Seizures were the SLE onset symptom for three patients, appeared during the active disease in two cases, and occurred during a period of clinical remission in one patient. In all cases we documented the association of epilepsy with the MTHFR mutation: the homozygosity form was present in one case (16.7%), and heterozygosity in five cases (83.3%). Nevertheless, levels of homocysteine in plasma were in the normal range. Moreover, we found a decrease in the level of S protein values in one case, a high titre positivity of anticardiolipin antibodies (aCL) (IgG and IgM) in three patients and low titre positivity (IgG) in one patient, and lupus anticoagulant (LAC) positivity in four cases. In conclusion, we believe that the abnormalities of coagulation present in our patients could be related to epileptogenesis or to an alteration of the seizure threshold.