Hepatic Function and Fibrinolysis in Patients with Hereditary Angioedema Undergoing Long-Term Treatment with Tranexamic Acid

Prophylactic treatment with antifibrinolytic agents, epsilon-aminocapriod and tranexamic acid, reduces the incidence and severits of attacks in patients with hereditary angioedema. Long-term ellectivenessor risk of antifibrinolytic agents has not been established. Sixteen patients needing continuous prophylaxis because of frequency and severity of attacks were treated with tranexamic acid. In four patients this treatment was ineffective and the drug was withdrawn after 2 months. A remission or reduction in the frequency or serverity of attacks was observed in 12 patients treated for a period ranging from 8 to 34 months. Hepatic tests and blood fibrinolytic activity were not influenced by long term oral treatment with tranexamic acid.     

Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.     

Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice versa: a case-control study

The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases. The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR = 4.1; two or more, OR = 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR = 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).     

Incidence and characteristics of non-Hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias

BACKGROUND: Some patients with cryoglobulinemic syndrome (CS) develop frank non-Hodgkin lymphoma (NHL), but the incidence and timing of this event are still poorly defined. METHODS: A retrospective multicenter study was performed of hepatitis C virus-positive patients with CS observed in 11 Italian centers belonging to the Italian Group for the Study of Cryoglobulinemia. RESULTS: The inclusion criteria were satisfied by 1,255 patients. During a cumulative follow-up of 8,928 patient-years, 59 cases of NHL were diagnosed, for an estimated rate of 660.8 new cases per 100,000 patient-years with 224.1 new cases of aggressive NHL subtypes per 100,000 patient-years. More than 90% of the patients developing NHLs had type II cryoglobulins. The NHLs were classified as nonaggressive in 31 cases (53%), aggressive in 20 (34%), and mucosa-associated lymphoid tissue lymphomas in 6 (10%); 2 cases were unclassifiable. The median time from the diagnosis of CS to the clinical onset of NHL was 6.26 years (range, 0.81-24 years). The clinical course and response to chemotherapy in the patients with CS who had NHL were similar to those usually described in patients with NHL without CS; the course of the CS only marginally benefited from chemotherapy. CONCLUSIONS: The overall risk of NHL in patients with CS is about 35 times higher than in the general population (12 times higher if nonaggressive lymphomas are excluded). The presence of CS did not significantly affect the treatment of newly diagnosed lymphomas.     

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.     

Deposits of IgD in renal disease. Immunohistological study of 180 renal biopsies

Abstract. IgD deposits have been investigated by an indirect immunofluorescence technique in 180 renal biopsies carried out on patients with various renal diseases. IgD was not present in nephrotic syndrome with minimal changes or focal glomerulosclerosis, in mesangial proliferative glomerulonephritis, in chronic advanced glomerulonephritis, in rheumatoid purpura and in other various nephropathies with predominant non-glomerular lesions. Significant deposits of IgD were identified in 12 out of 16 cases of membranoproliferative glomerulonephritis, in 15 out of 23 cases of membranous nephropathy, in 11 out of 21 cases of focal proliferative glomerulonephritis with mesangial IgA deposits, in 2 out of 5 cases of proliferative glomerulonephritis with crescents and in 1 out of 6 cases of proliferative exudative glomerulonephritis. All cases of lupus nephritis and nephritis associated with mixed cryoglobulinaemia showed IgD deposits. In diabetic glomerulosclerosis, IgD was found in 1 out of 4 biopsies and only in the exudative lesions. In 5 out of 8 cases of amyloidosis anti-IgD serum stained the amyloid substance irregularly. In such cases IgD was found in association with other immunoglobulins and complement with the same localization. These findings suggest that IgD may participate in the immunological processes which lead to the development of glomerular deposits, mainly in cases of chronic glomerular diseases.     

Deposits of IgD in Renal Disease. Immunohistological Study of 180 Renal Biopsies

Abstract. IgD deposits have been investigated by an indirect immunofluorescence technique in 180 renal biopsies carried out on patients with various renal diseases.
IgD was not present in nephrotic syndrome with minimal changes or focal glomerulosclerosis, in mesangial proliferative glomerulonephritis, in chronic advanced glomerulonephritis, in rheumatoid purpura and in other various nephropathies with predominant non-glomerulor lesions.
Significant deposits of IgD were identified in 12 out of 16 cases of membranoproliferative glomerulonephritis, in 15 out of 23 cases of membranous nephropathy, in 11 out of 21 cases of focal proliferative glomerulonephritis with mesangial IgA deposits, in 2 out of 5 cases of proliferative glomerulonephritis with crescents and in 1 out of 6 cases of proliferative exudative glomerulonephritis.
All cases of lupus nephritis and nephritis associated with mixed cryoglobulinaemia Bhowed IgD deposits.
In diabetic glomerulosclerosis, IgD was found in 1 out of 4 biopsies and only in the exudative lesions.
In 5 out of 8 cases of amyloidosis anti-IgD serum stained the amyloid substance irregularly. In such cases IgD was found in association with other immunoglobulins and complement with the same localization. These findings suggest that IgD may participate in the immunological processes which lead to the development of glomerular deposits, mainly in cases of chronic glomerular diseases.     

Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis.

Quantitative measurement of serum monoclonal protein (M-protein) is one of the most important tools for monitoring disease activity in monoclonal gammopathies. The aims of this study were to evaluate serum M-protein quantification by capillary zone electrophoresis (CZE) and to compare results with those obtained by densitometric scanning of high-resolution agarose gel electrophoresis (HRE-AGE). The evaluation was carried out on 82 samples from patients with various monoclonal gammopathies. All the suspected M-proteins were confirmed and characterised by immunofixation on agarose gel (IFE). CZE was performed on a Paragon CZE 2000 system (Beckman Coulter). Passing-Bablok regression was: y (CZE)=1.27 x(HRE-AGE)-5.21 g/L. The correlation coefficient was 0.92. Bland-Altman analysis demonstrated a mean difference of -1.83 g/L (95% CI -0.76 to -2.90) with clear evidence of a concentration-related bias. Densitometry gave higher values at low M-spikes (<20 g/L), whereas CZE gave higher values at large M-spikes (>20 g/L). The concentration-related bias was found to be independent of the immunoglobulin isotype. In conclusion, to compare previous results obtained by M-protein densitometric scanning with those obtained by direct measurement of CZE peaks, the calculation of a univocal transforming factor appears to be unreliable.