Flavia Del Porto

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.

Inflammation and immune response in acute aortic dissection.

Abstract Objective. The aim of our study was to evaluate the lymphocyte subpopulations and the cytokines in the peripheral blood of patients with type-A Stanford acute aortic dissection (AAD group) and to determine whether inflammatory cells are present at the site of aortic dissection. Methods. Thirty-five consecutive patients with type-A Stanford dissection were evaluated for haemochrome and lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD4+CD25+, CD16+CD56+, CD4+CD28−, CD8+CD28−) by flow cytometry. C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), and monocyte chemoattractant protein (MCP)-1 were measured by ELISA. In addition, immunohistochemical staining with cell type-specific antibodies was performed to study the inflammatory cells detected inside the aortic wall. Results. In the AAD group, a significant increase in natural killer (NK) (P = 0.032), B cells (P = 0.022), and CD8+CD28− (P = 0.045) subpopulations was observed, whereas there was a significant decrease in total T lymphocytes (P = 0.004) and T helper fractions (P = 0.005). Moreover, a significant increase in CRP (P < 0.0001), IL-6 (P < 0.0001), IL-8 (P < 0.0001), IL-10 (P < 0.0001), TNF-α (P < 0.0001), and MCP-1 (P < 0.001) was observed; macrophages represented the main population detected inside the media. Conclusions. Our results strongly support the hypothesis of a pivotal role of innate immunity in type-A Stanford AAD.

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.

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.

The multitasking role of macrophages in Stanford type A acute aortic dissection.

Objectives: The aim of the study was to determine whether the release by macrophages of matrix metalloproteinase (MMP)-12 and vascular endothelial growth factor (VEGF) - leading to inflammation, matrix degradation and neoangiogenesis - represents an effective pathway that underlies aortic wall remodeling in Stanford type A acute aortic dissection (AAD). Methods: Twenty-one consecutive patients with no genetic predisposition, with Stanford type A AAD were selected. In each patient, the levels of serum VEGF, MMP-12, serum interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1 were evaluated using enzyme-linked immunosorbent assay. Ascending aortic specimens were collected for immunohistochemical identification of any presence of inflammatory infiltrate, VEGF and CD31 expression. Results: A significant increase in serum VEGF (p = 0.044), MMP-12 (p = 0.007), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and MCP-1 (p = 0.0001) levels was observed in the AAD group compared to the control group. Furthermore, all AAD samples were positive for VEGF in the tunica media and showed vessel growth and immune-inflammatory infiltrate. A large number of cases (62.79%) showed inflammation at the edge of the dissection and approximately half (51.42%) showed neovessels growing at the edge of the dissection. Conclusions: The results suggest that VEGF-mediated angiogenesis and matrix degradation play a role in AAD. Finally, we believe that MMP-12 should be considered a marker of AAD.

Nerve Growth Factor and Brain‐Derived Neurotrophic Factor Levels in Patients with Rheumatoid Arthritis Treated with TNF‐α Blockers

Abstract:  Twenty consecutive rheumatoid arthritis (RA) patients (mean age 50.4 ± 10.5 years; 17 females; mean disease duration 5.78 ± 3.75 years) enrolled for tumor necrosis factor‐α (TNF‐α) blockers therapy (10 infliximab and 10 etanercept) were selected. Before starting therapy, 3 and 6 months thereafter all patients were evaluated for disease activity score (DAS), erythrocyte sedimentation rate (ESR), serum levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), nerve growth factor (NGF), and brain‐derived neurotrophic factor (BDNF). After 3 and 6 months a significant reduction in DAS, ESR, CRP, and IL‐6 was observed, whereas no significant differences of NGF and BDNF serum levels were found. These preliminary results confirm that TNF‐α blockers significantly improve disease activity and inflammation in RA; nevertheless further studies are needed to explain the mechanisms regulating NGF and BDNF release in RA patients treated with TNF‐α blockers.

Stanford-A acute aortic dissection, inflammation, and metalloproteinases: A review

Acute aortic dissection (AAD) is a life-threatening disease with an incidence of about 2.6–3.6 cases per 100,000/year. Depending on the site of rupture, AAD is classified as Stanford-A when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B when the descending thoracic aorta and/or aortic abdominal tract are targeted. It was recently shown that inflammatory pathways underlie aortic rupture in both type A and type B Stanford AAD. An immune infiltrate has been found within the middle and outer tunics of dissected aortic specimens. It has also been observed that the recall and activation of macrophages inside the middle tunic are key events in the early phases of AAD. Macrophages are able to release metalloproteinases (MMPs) and pro-inflammatory cytokines which, in turn, give rise to matrix degradation and neoangiogenesis. An imbalance between the production of MMPs and MMP tissue inhibitors is pivotal in the extracellular matrix degradation underlying aortic wall remodelling in dissections occurring both in inherited conditions and in atherosclerosis. Among MMPs, MMP-12 is considered a specific marker of aortic wall disease, whatever the genetic predisposition may be. The aim of this review is, therefore, to take a close look at the immune-inflammatory mechanisms underlying Stanford-A AAD.

MMP-12 as a new marker of Stanford-A acute aortic dissection

Abstract Background. The study evaluated macrophage cytokines and macrophage metalloprotease (MMP)-12 levels in patients with Stanford-A acute aortic dissection (AAD) and in patients with critical carotid artery stenosis (CAS) compared with patients matched for age, sex, and traditional cardiovascular risk factors (RF). The aim was to identify possible early serum markers of risk for atherosclerotic complications. Materials and methods. We selected 65 patients: 23 AAD patients, 21 CAS patients, 21 RF, and 10 healthy subjects (HS). In each patient and control serum, levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), and MMP-12 were assessed by ELISA. Results. A significant increase of MMP-12, IL-6, and IL-8 levels in AAD versus CAS was found. Moreover, MMP-12 was shown to be significantly higher in AAD versus RF, but not in CAS versus RF. A significant increase of IL-6, IL-8, MCP-1, TNF-α, and VEGF levels was observed both in AAD and CAS versus RF. Conclusions. The results suggest that MMP-12 may be considered to be a specific marker of Stanford-A AAD. Furthermore, the study confirmed that in AAD and CAS macrophage cytokines play a key role in the progression of the atherosclerotic disease towards complications.

Primary Antiphospholipid Syndrome Cerebral Atrophy: A Rare Association?

Neurologic complications are common in patients with antiphospholipid syndrome. In this article, we report the case of a young woman with neurologic disorders, a history of hypertension and transient ischemic attacks, and cerebral atrophy associated with primary antiphospholipid syndrome (PAPS). Magnetic resonance imaging of the brain showed multiple ischemic lesions and remarkable atrophy of frontal and parietal lobes. Cerebral atrophy in patients with PAPS can be considered as a feature of this disease. The case is discussed on the basis of relevant past literature. Although there are few reports on neuroradiologic findings in patients with PAPS, cerebral atrophy has been described. Because PAPS is more frequently recognized today than in the past, this condition should be included in the differential diagnosis of cerebral atrophy, particularly in young patients.

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.