IgG,kappa monoclonal gammopathy of unknown significance with AL amyloidosis simulating giant cell arteritis.

Monoclonal gammopathies complicated by AL amyloidosis can mimic giant cell arteritis (GCA). We hereby present the case of a 63 year old woman in whom symptoms consistent with GCA were the first manifestations of a monoclonal gammopathy of unknown significance (MGUS) associated with amyloidosis. A 63 year old woman was admitted for temporal headache, maseterine claudication, neck and shoulder stiffness. She was recently diagnosed with carpal tunnel syndrome. On physical examination she had prominent temporal arteries, macroglosia and orthostatic hypotension. Muscular strength was normal. She had high ESR and CRP; in this clinical context, GCA was suspected. A gamma spike on serum protein electrophoresis raised the suspicion of monoclonal gammopathy (MG). Immunoelectrophoresis revealed monoclonal bands for IgG and kappa chains. Massive deposits of amyloid and no inflammation were found on temporal artery biopsy. Multiple myeloma and lymphoma were ruled out. A diagnosis of AL amyloidosis complicating MGUS was formulated. She did well on therapy with bortezomib, cyclophosphamide and dexamethasone. Cases published in medical literature reveal amyloidosis mimicking GCA in the setting of established MGUS. As far as we know, this is the first case of MGUS with IgG and kappa chains in which a GCA-like picture induced by amyloidosis was present from the very onset.

Quantification and molecular characterization of regulatory T cells in connective tissue diseases.

The aim of our study was to investigate and characterize regulatory T cells (Treg) in peripheral blood of patients with connective tissue diseases (Systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, poly- and dermatomyositis) as compared with blood from healthy controls. Treg cells were quantified and phenotypically characterized by flow cytometry while the expression level of Foxp3 mRNA was evaluated by real time PCR. A reduced percentage of peripheral blood Treg cells was found in patients than in controls, irrespective of the type of connective tissue disease. Treg cells, especially those expressing one of the phenotypical markers, seemed to differ not only between patients and healthy controls but also among types of diseases. Additionally, the presence of autoantibodies as well as disease activity appeared to be correlated with particular Treg cell populations, especially those expressing one of the examined phenotypical markers. Correlations with therapy suggested that glucocorticoids plus antimalarial or other immunosuppressor drugs diminished the percentage of Treg cells, especially of those with memory phenotype. These findings indicated dysregulations at the level of Treg cells and suggested an involvement of these cells in the pathology of connective tissue diseases. Moreover, our data are in agreement with the suggestion that Treg cells could be therapeutic targets for some autoimmune diseases.

[Wegener granulomatosis with severe alveolar hemorrhagic syndrome]. / Granulomatoza Wegener cu sindrom de hemoragie alveolara severa.

The article presents the case of a female admitted for the suspicion of pulmonary TB (clinical and radiological pattern compatible with this diagnosis), in which the lack of bacteriological confirmation together with a rapid and dramatic deterioration of clinical, radiological and functional status excluded tuberculosis and oriented the diagnosis towards a severe alveolar hemorrhage; further tests confirmed a Wegener granulomatosis with pulmonary, renal and ORL manifestations. The evolution was rapidly favorable using pulse-therapy with cyclophosphamide and methylprednisolone i.v. The particularities of this case were: the use of helmet device for correction of the extremely severe hypoxemia for 3 weeks (no other studies reported such a long continuous duration of use of this device) and the lag between the pulmonary and the renal impairment.

Roles of CD147 on T lymphocytes activation and MMP-9 secretion in systemic lupus erythematosus.

The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 x CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs.

Plasma markers of endothelial dysfunction in type 2 diabetics.

BACKGROUND: Type 2 diabetes, or non-insulin-dependent diabetes mellitus, represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Atherosclerotic lesions occur in diabetic patients at an earlier age with severe clinical manifestations and poor outcome. Our objective was to investigate the correlation between lipoprotein-associated phospholipase A2 (PLA2-LDL), myeloperoxidase (MPO), and paraoxonase (PON), enzymes implicated in the evolution of endothelial dysfunction associated with type 2 diabetes. METHODS: One hundred diabetic patients [50 without documented coronary artery disease (group 1) and 50 with CVD (group 2)] and 46 healthy controls were investigated for PLA2-LDL, MPO, and PON activities. RESULTS: PLA2-LDL activity was significantly higher in group 2 than in group 1 and among controls. PON activity was lower in group 1 than in controls, reaching the lowest level in group 2. MPO activity was higher in type 2 diabetics than among controls, with similar values in groups 1 and 2. CONCLUSIONS: The evaluation of PLA2-LDL, MPO, and PON activities may improve early diagnosis of CVD in asymptomatic patients with type 2 diabetes and can help to evaluate accelerated atherosclerosis and microvascular disease.

The significance of human platelet-activating factor-acetylhydrolase in patients with chronic stable angina.

BACKGROUND: Inflammatory reactions within coronary atherosclerotic plaques are increasingly thought to be crucial determinants of the clinical course in patients with coronary artery disease (CAD). Platelet-activating factor-acetylhydrolase (PAF-AH) is considered to reflect the ongoing inflammatory process in patients with CAD. Our objective was to determine the activity of PAF-AH in patients with stable angina and its correlations to lipoprotein levels and the inflammatory status of the patient. METHODS: Forty-five patients with documented CAD and stable angina and 20 controls were investigated for PAF-AH activity, lipoprotein levels, and peripheral neutrophil (PMN) activity. RESULTS: Patients were divided into two groups according to the values of PAF-AH activity (group 1: 250 IU/l). A correlation was observed between PAF-AH activity and LDL-C and HDL-C in controls and in all patients. The percentage of granulocytes generating intracellular O(2)(-) in unstimulated PMN was higher in group 2 patients than in group 1 patients and controls. The phagocytic activity of PMNs had an inverse correlation with PAF-AH in group 2. High intracellular O(2)(-) generation was coupled with low extracellular release of the anion and phagocytosis impairment in group 2. During the follow-up period, some of the patients in group 2 displayed a worsening of the clinical state and/or resting ECG changes. CONCLUSIONS: PAF-AH activity in patients with stable angina is correlated with hyperlipemia and a high PMN activation state, and it may be considered a potential predictor of vascular risk.

Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

Matrix metalloproteinase-9 (MMP-9) was involved in inflammation and immune system dysfunctions. Besides immunologic abnormalities, systemic lupus erythematosus (SLE) also presents chronic inflammatory components. Therefore, a role of MMP-9 in SLE pathology might be supposed. To verify this hypothesis, SLE patients and healthy donors were compared for the MMP-9 and MMP-9 mRNA levels in peripheral blood mononuclear cells (PBMCs), the spontaneous secretion of MMP-9 and TIMP-1 and the MMP-9 activity. Thus, we found that fresh PBMCs from SLE patients expressed a significantly higher activity of MMP-9 and spontaneously released higher levels of MMP-9, as compared to healthy donors, while the secreted TIMP-1 level was the same for both groups. When the patients were sub-grouped based on disease status, the most increased pro-MMP-9 activity inside the PBMCs was identified for relapse SLE sub-group. A similar observation for SLE patients with positive serum fibrinogen was found. Following culture, the PBMCs from remission SLE patients secreted significantly higher MMP-9 level, than the PBMCs from relapse SLE patients. PBMCs from relapse SLE patients secreted the highest levels of TIMP-1, although this difference was not statistically significant. Taken together, these observations suggested the multiple roles of MMP-9 and TIMP-1 in progress of inflammation and tissue damage and/or in repair, depending on clinical stages of SLE.