Erythrocyte deformability profile evaluated by laser diffractometry in patients with multiple myeloma: Re-examination of our cases.

BACKGROUND: Multiple myeloma is a complex pathology which represents about 10 % of all hematological neoplasms. It can often present changes in the hemorheological profile and, in relation to this last topic, our aim is to evaluate the hemorheological profile in a group of multiple myeloma patients, with reference to erythrocyte deformability. METHODS: We have examined the profile of the erythrocyte deformability in multiple myeloma enrolling 29 patients; this profile, expressed as elongation index at several shear stress, has been obtained using the diffractometric method. RESULTS: By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, but we did not observe any significant differences about this profile subdividing the whole group of MM patients according to the degree of bone marrow plasma cell infiltration, to the red blood cell distribution width and to the serum values of LDH. CONCLUSIONS: In this paper we have taken in consideration all the hypothesis for a possible explanation of the behaviour of this a reduced erythrocyte deformability in multiple myeloma. Erythrocyte deformability interferes with the physiological release of oxygen to tissues, with several clinical implications.

Reflections on the unexpected laboratory finding of hemorheological alterations observed in some haematological disorders.

Hyperviscosity syndrome is a clinical condition characterized by the slowing of blood flow through the vessels and it may be associated with several diseases. The nosographic classification of primary hyperviscosity conditions (Wells classification 1970) divided the primary hyperviscosity syndromes in polycythaemic, sclerocytemic and sieric. Recent and personal laboratory observations have highlighted an unexpected behaviour of the erythrocyte deformability observed in some haematological disorders such as polycythemia vera, multiple myeloma and monoclonal gammopathy of undetermined significance. The interest of this observation depends on the fact that up to now, according to the Wells classification, the hemorheological alteration present in PV was related to the increase of RBC mass while that present in MM and MGUS was attributable to the abnormality of plasma or serum viscosity only. Through an extensive research among the literature, using MEDLINE/PubMed to identify all published reports on the hyperviscosity syndromes, issues that until now have been dealt with separately will therefore be analyzed in a unique paper, allowing a global view. The aim of this paper is to provide some suggestions for reflection and emphasizing the need of a nosographic framework of hyperviscosity that, probably, deserves to be reviewed.

Expression pattern of matrix metalloproteinases-2 and -9 and their tissue inhibitors in patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Matrix metalloproteinases (MMPs) are a heterogeneous family of endopeptidases that play a role in many physiological functions, including the immune response. An imbalance between the activity of MMPs and their physiological tissue inhibitors (TIMPs) has been proposed in the pathophysiology of different autoimmune disorders. We aimed to assess the plasmatic levels of MMP-2, MMP-9, and their inhibitors TIMP-1 and -2 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). SUBJECTS AND METHODS: Twenty patients with CIDP and 20 age- and sex-matched healthy controls were enrolled. Plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by the enzyme-linked immunosorbent assay. RESULTS: CIDP subjects had higher MMP-9 concentrations along with TIMP-1 downregulation when compared to controls, with the consequent increase in the MMP-9/TIMP-1 ratio (p<0.000002 for all measures). Conversely, the concentration of MMP-2 was lower in the CIDP group (p<0.01) without changes in the TIMP-2 concentration. The MMP-2/TIMP-2 ratio was decreased in the patients' group (p<0.02). DISCUSSION: We provide first preliminary evidence that the plasmatic pattern of MMPs and TIMPs is markedly altered in patients with CIDP. Future studies are needed to assess the potential usefulness of these new biomarkers in the clinical setting.

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity.

The association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30-35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.

Matrix Metalloproteases in Arterial Hypertension and their Trend after Antihypertensive Treatment.

BACKGROUND/AIMS: Arterial hypertension is characterized by vascular remodelling, atherosclerosis and cardiovascular complications. Matrix metalloproteases (MPPs) are endopeptidases produced by all the cells present in the vascular wall and are involved in the regulation of the extracellular matrix protein turnover. MMPs contribute to blood vessel formation, remodelling, angiogenesis; whereas an altered expression or activity of MMPs or their tissue inhibitors (TIMPs) results correlated with the development and progression of cardiovascular complications. METHODS: We examined the literature data regarding the role of MMPs in human hypertension, including their involvement in vascular remodelling, and the effects of some antihypertensive molecules on these MMP/TIMP profile. RESULTS: The expression and the activity of some MMPs and TIMPs are impaired in human hypertension. An altered MMPs/TIMPs balance plays an important role in the vascular wall rearrangement, in response to hemodynamic changes which may induce myocardial hypertrophy and fibrosis leading to ventricular remodelling. Several studies have examined the effects of some antihypertensive molecules, such as ACE inhibitors, angiotensin receptor blockers, calcium-channel blockers, and aldosterone antagonists, on the MMPs/TIMPs profile by obtaining positive results. CONCLUSION: Considering the data taken into consideration, the authors believe that in clinical practice a strategic antihypertensive therapy directed to the MMPs profile, may be useful to decrease the risk of cardiovascular complications.

Nutritional predictors of mortality after discharge in elderly patients on a medical ward.

BACKGROUND: Malnutrition in elderly inpatients hospitalized on medical wards is a significant public health concern. The aim of this study was to investigate nutritional markers as mortality predictors following discharge in hospitalized medical elderly patients. MATERIALS AND METHODS: This is a prospective observational cohort study with follow-up of 48 months. Two hundred and twenty-five individuals aged 60 and older admitted from the hospital emergency room in the past 48 h were investigated at the medical ward in the University hospital in Palermo (Italy). Anthropometric and clinical measurements, Mini-nutritional Assessment (MNA) questionnaire, bioelectrical (BIA) phase angle (PA), grip strength were obtained all within 48 h of admission. Mortality data were verified by means of mortality registry and analysed using Cox-proportional hazard models. RESULTS: Ninety (40%) participants died at the end of follow-up. There were significant relationships between PA, MNA score, age and gender on mortality. Patients in the lowest tertile of PA (< 4·6°) had higher mortality estimates [I vs II tertile: hazard ratio (HR) = 3·40; 95% confidence interval (CI): 2·01-5·77; II vs III tertile: HR = 3·83; 95% CI: 2·21-6·64; log-rank test: χ(2) = 43·6; P < 0·001]. Similarly, the survival curves demonstrated low MNA scores (< 22) were associated with higher mortality estimates (HR = 1·85; 95% CI: 1·22-2·81 χ(2) = 8·2; P = 0·004). CONCLUSIONS: The MNA and BIA-derived phase angle are reasonable tools to identify malnourished patients at high mortality risk and may represent useful markers in intervention trials in this high-risk subgroup.

Acid-base and electrolyte abnormalities in heart failure: pathophysiology and implications.

Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in subjects with congestive heart failure. This may be due either to the pathophysiological alterations present in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), or to the adverse events of therapy with diuretics, cardiac glycosides, and ACE inhibitors. Subjects with heart failure may show hyponatremia, magnesium, and potassium deficiencies; the latter two play a pivotal role in the development of cardiac arrhythmias. The early identification of these alterations and the knowledge of the pathophysiological mechanisms are very useful for the management of these patients.

Obstructive Sleep Apnea Syndrome: Links Betwen Pathophysiology and Cardiovascular Complications.

PURPOSE: The prevalence of obstructive sleep apnea syndrome (OSAS) is increasing, especially in the middle-aged population. OSAS is associated with an elevated risk of cardiovascular morbidity and mortality. Arterial hypertension is often the first consequence of OSAS, but the most severe complications are coronary artery disease, stroke and arrhythmias. The aim of this review was to analyze the several mechanisms involved in the development of the cardiovascular events, such as endothelial dysfunction accompanied by a pro-inflammatory and pro-oxidant status, hemorheological alterations, hypercoagulability and imbalance between matrix metalloproteases and their inhibitors. SOURCE: A search on PubMed was carried out using the following terms: obstructive sleep apnea syndrome; endothelial dysfunction; oxidative stress; inflammation; rheology; matrix metalloproteases. PRINCIPAL FINDINGS: OSAS severity strongly influenced cardiovascular risk factors and, furthermore, it was correlated with the incidence of fatal and non-fatal events. CONCLUSIONS: The treatment with continuous positive airways pressure (cPAP) is the gold standard for OSAS and was able to positively influence all the pathophysiological mechanisms responsible for cardiovascular diseases. Long-term cPAP improved endothelial function and hemorheology, reduced oxidative stress and inflammation, and decreased the levels of metalloproteases.

Neutrophil/HDL-C, Lymphocyte/HDL-C and Monocyte/HDL-C in subjects with asymptomatic carotid atherosclerosis.

BACKGROUND: Leukocyte count is a prognostic marker for cardiovascular diseases, with key role in atherosclerosis development. Specific number of neutrophils, lymphocytes and monocytes can predict cardiovascular risk, also in asymptomatic subjects. Among the lipoprotein fractions, HDL-C is a protective factor in the cardiovascular disorders. For the above reason, we have examined the peripheral count of leukocytes, neutrophils, lymphocytes and monocytes, and the ratios between neutrophils/HDL-cholesterol, lymphocytes/HDL-cholesterol, and monocytes/HDL-cholesterol, to evaluate the possible utility of the obtained values in progression of asymptomatic carotid atherosclerosis. METHODS: We performed our analysis in a cohort of 100 subjects with asymptomatic carotid atherosclerosis, of which 43 men and 57 women. The data were expressed as medians and IQR. To analyse the differences in leukocyte, neutrophil, lymphocyte, monocytes count and their ratio with HDL-cholesterol the Mann-Whitney test was employed. RESULTS: The peripheral count of leukocyte subtypes and the ratios, they change in relation to the number of cardiovascular risk factors and the degree of insulin resistance. CONCLUSIONS: In this cohort of subjects, the percentage of observed cardiovascular risk factors significantly affect some leukocyte parameters. These results, allow us to underline the importance of the leukocyte indices in the evaluation of subjects with asymptomatic vascular atherosclerosis.

Thrombotic Risk and Calculated Whole Blood Viscosity in a Cohort of Patients With New Diagnosis of Multiple Myeloma.

The pathogenesis of venous thromboembolism in multiple myeloma is still poorly understood because multiple factors are involved. In particular, the increase in whole blood viscosity has a key role and, therefore, we performed an evaluation of some hemorheological determinants in multiple myeloma patients, putting them in relation to the thrombotic risk, with the aim to evaluate if an alteration of the hemorheological pattern was associated with a higher thrombotic risk. We performed an observational retrospective cohort study with data collected from January 2017 to September 2022. In a group of 190 patients with newly diagnosed multiple myeloma, we have examined the trend of calculated blood viscosity according to the Merrill formula, and we stratified the patients for the thrombotic risk in accordance with the IMWG/NCCN guidelines and with IMPEDE VTE score. Using the thrombotic risk stratification proposed by IMWG/NCCN any variation in calculated blood viscosity is evident, while, with the IMPEDE VTE score, we observed an increase in calculated blood viscosity in patients with "intermediate + high" risk. The calculated blood viscosity is higher in subjects presenting an "intermediate + high" thrombotic risk according to the IMPEDE VTE score. This association could therefore lay the groundwork for further research with the aim to confirm the role of hemorheological pattern in MM-related thrombotic risk.

Pro-inflammatory genetic markers of atherosclerosis.

Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine.

Protein oxidation in metabolic syndrome.

PURPOSE: Oxidative stress plays a pivotal role in the pathogenesis of the metabolic syndrome and in the progression of its complications. Carbonylated proteins are a stable marker of severe oxidative stress because damage to the protein structure is irreversible and may cause an inhibition of their enzymatic activity or an increased susceptibility to proteolysis. There are few data regarding protein oxidation in metabolic syndrome, although elevated levels of carbonyl groups are often detected in subjects with obesity, diabetes mellitus, hypertension or dyslipidemia, well-known components of the metabolic syndrome. In particular, obesity, insulin resistance and diabetes mellitus are frequently associated with increased protein carbonylation. A relationship between insulin resistance, protein oxidative stress and inflammation has also been suggested as well as protein oxidation products are correlated with overexpression of resistin, TNF-α and IL-6. CONCLUSION: Therapeutic interventions based on lifestyle modifications and pharmacological agents in order to correct all the main risk factors influence oxidative stress and protein carbonylation.

Red Blood Cell Distribution Width, Erythrocyte Indices, and Elongation Index at Baseline in a Group of Trained Subjects.

BACKGROUND: Regular exercise elicits adaptive changes in several organs and physiological processes, including erythrocyte properties. METHODS: In a group of 79 subjects (62 men and 17 women; mean age 31.37 ± 10.19 years) who trained several times a week as they practiced amateur sports, we evaluated the elongation index, markers of erythrocyte deformability, red blood cell distribution width (RDW), indicators of erythrocyte anisocytosis, hematocrit, hemoglobin, and the main erythrocyte indices (MCV, MCH, MCHC) in basal conditions. RESULTS: In comparison with a group of healthy, but not training, volunteers, the values of the elongation index, and not the RDW, are increased, and this datum is accompanied by an increase in MCV and MCHC, likely related to an increased presence of circulating young erythrocytes in training subjects. We also divided the same group according to the median of the VO2max, observing that the subgroup above the median shows both an increase in the elongation index values and a decrease in MCH and MCHC. CONCLUSIONS: In trained subjects, there is no correlation between the values of the elongation index and the RDW, while the interrelations among the elongation index, RDW, and main erythrocyte indices appear to be of particular interest and of a certain complexity.

Polymorphonuclear phenotypical expression of CD18, at baseline and after in vitro activation, in several clinical disorders: Revision of our case series.

BACKGROUND: In relation to the different and important roles of the beta2 integrins, we have revisited the expression of polymorphonuclear leukocyte CD18 in several clinical disorders, at baseline and after in vitro activation. SUBJECTS: we have examined subjects with type 1 diabetes mellitus, vascular atherosclerotic disease, type 2 diabetes mellitus without and with macrovascular complications, chronic renal failure on conservative treatment, essential hypertension, deep venous thrombosis, acute ischemic stroke and subjects with venous leg ulcers. METHODS: unfractioned leukocyte suspension was prepared according to the Mikita's method, while the leukocyte were separated into mononuclear and polymorphonuclear cells with a Ficoll-Hypaque medium. Using specific monoclonal antibody, the CD18 expression was evaluated with cytofluorimetric analysis, using FACScan (Becton Dickinson) be Cellquest software; the activation in vitro with PMA was effected according to modified Yasui and Masuda methods. RESULTS: in type 1 diabetes mellitus, at baseline CD18 is under expressed in comparison with normal control, and not changes after PMA activation were observed; in subjects with vascular atherosclerotic disease, in type 2 diabetes mellitus CD18 is over expressed at baseline but does not vary after activation; in subjects with chronic renal failure, essential hypertension and in subjects with acute ischemic stroke the CD18 up-regulate at baseline compared to normal control, and it increases further after activation; in subjects with deep venous thrombosis the CD18 expression is not different from control group at baseline, but it increases after activation; finally, in subjects with venous leg ulcers the CD18 is normally expressed at baseline, and it does not change after PMA activation. CONCLUSIONS: in the different clinical disorders, the trend of this integrin subunit provides some specific information, useful to select the best therapeutic strategy in clinical practice.

Red Cell Distribution Width and Elongation Index in a Cohort of Patients With Juvenile Acute Myocardial Infarction.

In a cohort of patients with juvenile myocardial infarction, we considered the red cell distribution width (RDW), hematocrit, hemoglobin, and elongation index values at the initial phase and at 3 and 12 months from the acute event. In the initial phase, only the elongation index values turn out reduced if compared with those of the control group, and that only turn out to discriminate the infarcted ST-segment elevation myocardial infarction (STEMI) from non-STEMI. Dividing the patients according to the traditional risk factors and the extent of coronary heart disease, there are no significant variations in the analyzed parameters. No major changes are observed after 12 months from the acute event. Both to 3 and to 12 months from the infarct episode, the negative statistical correlation between RDW and the value of elongation index remains. These data make us reflect on the role of the degree of anisocytosis of red blood cell expressed by the RDW on the determinism of erythrocyte deformability, which plays its role in the microcirculation district and that is essential in the transfer of tissue oxygen.

Calculated Whole Blood Viscosity and Albumin/Fibrinogen Ratio in Patients with a New Diagnosis of Multiple Myeloma: Relationships with Some Prognostic Predictors.

BACKGROUND: In this single center study, we retrospectively evaluated the calculated hemorheological profile in patients with a new diagnosis of multiple myeloma, with the aim to evaluate possible relationships with some prognostic predictors, such as ISS, albumin levels, beta2-microglobulin, red cell distribution width, and bone marrow plasma cell infiltration. METHODS: In a cohort of 190 patients, we examined the calculated blood viscosity using the de Simone formula, and the albumin/fibrinogen ratio as a surrogate of erythrocyte aggregation, and then we related these parameters to prognostic factors, using the Kruskal-Wallis and the Mann-Whitney tests, respectively. RESULTS: From our analysis, it emerged that the evaluated hemorheological pattern differed in the three isotypes of multiple myeloma, and the whole blood viscosity was higher in IgA and IgG isotypes with respect to the light chain multiple myeloma (p < 0.001). Moreover, we observed that, as the ISS stage progressed, the albumin/fibrinogen ratio was reduced, and the same hemorheological trend was traced in subgroups with lower albumin levels, higher beta2-microglobulin and red cell distribution width RDW values, and in the presence of a greater bone marrow plasma cell infiltrate. CONCLUSIONS: Through the changes in blood viscosity in relation to different prognostic factors, this analysis might underline the role of the hemorheological pattern in multiple myeloma.

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations with increase in plasma viscosity. The high output heart failure in multiple myeloma is associated with significant morbidity and mortality, emphasizing the need for a multidisciplinary approach.

Uric acid and uric acid/creatinine ratio and their correlations with the hemorheological determinants in subjects with subclinical carotid atherosclerosis.

BACKGROUND AND OBJECTIVE: we have examined the concentration of serum uric acid and the serum uric acid/creatinine ratio as well as their correlations with the main determinants of the hemorheological profile in a group of subjects with subclinical carotid atherosclerosis. METHODS: we evaluated the concentration of serum uric acid and the serum uric acid/creatine ratio in 43 men and 57 women [median age 66.00 (25)] with subclinical carotid atherosclerosis, subsequently divided according to the number of traditional cardiovascular risk factors and to the insulin resistance degree. RESULTS: serum uric acid, but not the serum uric acid/creatinine ratio, results strongly influenced by the number of cardiovascular risk factors and by the insulin resistance degree. In the whole group and in the subgroups of subclinical carotid atherosclerosis subjects, serum uric acid and serum uric acid/creatinine ratio show significant correlation, besides with whole blood viscosity, with plasma viscosity and erythrocyte aggregation. The influence of the serum uric acid on the erythrocyte aggregability that is a part of the erythrocyte aggregation is to ascribe to the action carried out by serum uric acid on the erythrocyte zeta potential. CONCLUSIONS: it is reasonable to think that the treatment of the asymptomatic or symptomatic hyperuricemia with the urate-lowering therapy that reduces the serum uric acid concentration may reflect on the hemorheological profile which role on the atherosclerotic cardiovascular disease is well known.

Leukocyte subtypes, gelatinases, and their tissue inhibitors in a group of subjects with asymptomatic carotid atherosclerosis.

In a cohort of subjects with asymptomatic carotid atherosclerosis (ACA), we have evaluated the neutrophil and lymphocyte count and their ratio (NLR), the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). At baseline, no difference was observed between ACA subjects and subject control group regarding neutrophil and lymphocyte count while was evident in ACA subjects a significant increase in MMP-2, MMP-9 and TIMP-2 associated to a significant decrease in TIMP-1. Dividing the ACA according to the number of cardiovascular risk factors (CRFs) we have observed an increase in lymphocyte count in the subgroup with 3-5 CRFs. Evaluating the leukocyte subtypes according to all the surrogate markers of insulin resistance has been noted, in the subgroups that exceed the medians of these markers, a significant increase in neutrophil and lymphocyte count without any variation of the NLR. Effecting the same evaluation for the MMP/TIMP pattern we observed, instead, that the same subgroups tend to show a decrease in MMP-2 and an increase in MMP-9. No difference instead for TIMP-1 and TIMP-2. The abnormality of the MMP/TIMP pattern, bearing in mind the cardiometabolic clustering present in this cohort of ACA subjects, would induce to use drugs able not only to cure the cardiometabolic risk factors but also to influence the MMP/TIMP profile.

Metalloproteinases and Tissue Inhibitors in Generalized Myasthenia Gravis. A Preliminary Study.

INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have recently been proposed as promising biomarkers in different immune-mediated disorders. We evaluated the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors TIMP-1 and TIMP-2 in a patients' cohort with generalized myasthenia gravis (MG). METHODS: Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were evaluated in 14 patients with generalized MG and 13 age- and sex-matched healthy controls. The severity of disease was assessed by the modified Osserman classification. RESULTS: Compared to the healthy subjects, MG patients had increased plasma concentrations of MMP-9, but reduced plasma levels of MMP-2 and TIMP-1. MG patients also showed a positive correlation between MMP-2 concentrations and disease severity. An increase in MMP-9 levels and MMP-9/TIMP-1 ratio and a decrease in MMP-2 levels and MMP-2/TIMP-2 ratio were detected in patients with generalized MG. Higher levels of MMP-2 correlated with greater disease severity. DISCUSSION: Our preliminary findings suggest that MMPs and TIMPs could play a role in the pathogenesis of MG and might be associated with the risk of clinical deterioration.