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Giuseppe Guida

Publications and source records attributed to Giuseppe Guida.

10 recordsLinked to original sources
PubMed2006

Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations.

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.

ADP-ribosyl Cyclase 1↗
PubMed2006

Exhaled nitric oxide as a diagnostic test for asthma in rhinitic patients with asthmatic symptoms.

BACKGROUND: Rhinitis is a major risk factor for asthma, so that evaluation of the lower airways is recommended in patients with rhinitis. Exhaled nitric oxide (FE(NO)) is considered a marker of airway inflammation and it has been found to be useful for the screening of patients with suspected diagnosis of asthma. Our aim was to assess the validity and accuracy of FE(NO) to identify patients with asthma in 48 non-smoking patients with persistent rhinitis and asthma-like symptoms. METHODS: Asthma was diagnosed on the basis of 12% improvement in FEV1 after salbutamol or a methocholine PD(20)FEV1<800 microg. Prior to lung function FE(NO) was measured with the single exhalation method at 50 ml/s. RESULTS: The geometric mean (95% confidence interval) FE(NO) was significantly higher in the 18/48 asthmatics than in the non-asthmatic patients (60 ppb, CI 95%: 50-89, versus 30 ppb, CI 95%: 28-45, P=0.001). Receiver operating characteristic (ROC) curve for the diagnosis of asthma indicated that FE(NO) is an acceptable discriminator between patients with and without asthma (area under the ROC curve=0.78). None of the asthmatic patients had FE(NO) values<25 ppb and all the patients with FE(NO)>100 ppb (n=5) were asthmatics. The sensitivity and specificity of FE(NO) for detecting asthma, using 36 ppb as cut-off point, were 78% and 60% and the positive and negative predictive values were 54% and 82%, respectively. CONCLUSIONS: Measuring FE(NO) may be useful for the screening of rhinitic patients with asthma-like symptoms.

Adolescent↗
PubMed2006

Level of exhaled nitric oxide during human anaphylaxis.

BACKGROUND: Nitric oxide (NO) seems to play an important pathophysiologic role in modulating the systemic changes associated with anaphylaxis. Even if some effects of NO may be protective, animal models of anaphylaxis have shown that the summation effects of NO are deleterious, resulting in hypotension and loss of intravascular volume. There are no studies of NO production during anaphylaxis in humans. OBJECTIVE: To measure the level of exhaled NO during anaphylaxis induced by bee venom cluster immunotherapy in a 34-year-old beekeeper. METHODS: Exhaled NO was measured using a chemiluminescence analyzer at different flow rates, and alveolar NO concentration and airway NO production were calculated. RESULTS: We measured a high level of exhaled NO (78 ppb at 50 mL/s, with increased alveolar concentration and airway production) during anaphylaxis induced by bee venom immunotherapy in this patient. Normal values of exhaled NO were measured in the same patient 1 week later before and after a modified regimen of desensitization. CONCLUSIONS: Nitric oxide production was increased in the respiratory tract during anaphylaxis. Having excluded all the common causes of increased exhaled NO levels, these resultssupport the hypothesis that NO plays an important role in anaphylaxis.

Adult↗
PubMed2005

HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses.

We used a proteomic approach for identifying molecules involved in the pathogenesis of chronic lymphocytic leukemia (CLL). We investigated 14 patients who were completely concordant for IgV(H) mutational status (unmutated vs. mutated), CD38 expression (positive vs. negative), and clinical behavior (progressive vs. stable); these patients were characterized as having either poor or good prognoses. The 2 patient subsets differed in the expression of hematopoietic lineage cell-specific protein 1 (HS1). In patients with poor prognoses, most HS1 protein was constitutively phosphorylated, whereas only a fraction was phosphorylated in patients with good prognoses. This difference was investigated in a larger cohort of 26 unselected patients. The survival curve of all 40 patients analyzed revealed that patients with predominately phosphorylated HS1 experience a significantly shorter median survival time. As HS1 is a protein pivotal in the signal cascade triggered by B cell receptor (BCR) stimulation, we studied its pattern of expression following BCR engagement. Normal mature B cells stimulated by anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the more phosphorylated form. Naive B cells showed both HS1 forms while memory B cells expressed mainly the phosphorylated fraction. These data indicate a central role for antigen stimulation in CLL and suggest a new therapeutic target for patients with aggressive disease.

ADP-ribosyl Cyclase↗
PubMed2004

Allergy to pigeon tick (Argas reflexus): demonstration of specific IgE-binding components.

BACKGROUND: The European tick, Argas reflexus, is an urban pest parasitizing urban pigeons and may cause a wide range of allergic reactions. METHODS: Specific IgE to A. reflexus, SDS-PAGE and IgE immunoblotting, performed with tick extract, were carried out in the sera of 6 patients who reported allergic reactions after tick bite. RESULTS: Specific IgE to A. reflexus (RAST class ranging from 1 to 3) were detected in the sera of 6 patients who reported allergic reactions (urticaria and angioedema in 2 and anaphylaxis in the other 4 patients) after tick bite. IgE reactivity to two bands of 22 and 40 kDa were identified in the patient sera. CONCLUSIONS: Allergy to A. reflexus has to be considered in allergic patients living in buildings where pigeons have their nests. The powerful sensitizing property of tick allergen is underlined by the observation that none of our patients was atopic.

Adult↗
PubMed2004

Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene.

We studied immunoglobulin variable heavy-chain (IGHV) repertoire and mutational status in 553 patients with chronic lymphocytic leukemia (CLL) from the Mediterranean area to gain insight into the potential pathogenetic role of antigenic stimulation. The most commonly represented IGHV genes mirrored the usage of normal B cells, with the exception of IGHV1-18, IGHV3-30.3, and IGHV4-59 that were underrepresented. The IGHV3-21 gene, frequently expressed in Northern European CLL, was present only in 16 cases (2.9%). Based on HCDR3 cluster analysis, cases using IGHV3-21 could be grouped in 2 subsets of similar frequency. The first one (7 of 16 cases) carried a similar HCDR3 amino acid sequence (common-HCDR3 subset), virtually identical to the Scandinavian IGHV3-21 CLL. These cases used the IGHJ6 gene; 4 of 7 were unmutated; 6 of 7 carried the V(lambda)2-14 (IGLV3-21) light-chain gene with a similar LCDR3. All expressed CD38 and had a progressive disease. The second subset (9 of 16) was characterized by heterogeneous HCDR3 rearrangements (nonhomogeneous-HCDR3 subset), diverse IGHJ and IGV light-chain gene usage, variable IGHV mutational status (5 of 9 unmutated), variable CD38 expression, and variable clinical course (4 of 9 progressed). The first subset suggests a potential antigenic element rarely encountered in the Mediterranean area, possibly responsible for a negative outcome. The second subset may reflect the physiologic heterogeneity of expression of IGHV3-21 rearrangements in the normal repertoire and is characterized by a variable clinical outcome.

Adult↗
PubMed2003

Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly.

The responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal chronic lymphocytic leukemia (CLL)-like B lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 healthy subjects older than 65 years with no history or suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a kappa/lambda ratio of more than 3:1 or less than 1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like), and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non-CLL-like). In 2 subjects, 2 phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. Polymerase chain reaction (PCR) analysis demonstrated a monoclonal rearrangement of IgH genes in 15 of 19 cases. No bcl-1 or bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression, 13 additional CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like: 5.5%). Thus, phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly individuals and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B cells.

Aged↗
PubMed2002

The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression.

Chronic lymphocytic leukemia (CLL) has a variable clinical course. CD38 expression and IgV(H) gene mutational status are independent predictors of prognosis, but their relationships and the CD38 cutoff level are unknown. Using cytofluorography, we analyzed CD38 in 148 patients, in 108 of whom we were able to evaluate IgV(H) mutations, make correlations with disease history, and assess cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38(-), a group homogeneously CD38(+), and a group characterized by a bimodal profile, because of the concomitant presence of variable proportions of 2 distinct populations, one CD38(+) and one CD38(-). In CD38 bimodal expression patients the CD38(+) subset was significantly more represented in the bone marrow than in the peripheral blood. For IgV(H) mutations, 11.4% of CD38(-), 84.6% of CD38(+), and 68.0% of CD38 bimodal expression patients had no mutation. CD38 expression, IgV(H) mutational status, and traditional prognostic factors were concordant. The progression rate was 12.9% for CD38(-), 75.0% for CD38(+), and 63.3% for CD38 bimodal expression patients. Only 25.8% of the CD38(-) patients but 63.3% of the bimodal and 75.0% of CD38(+) patients were treated. The presence of a CD38(+) population, albeit small, correlated with the development of autoimmune manifestations. The CD38(-) group has not yet reached the median survival, which is 183 months in the CD38(+) group and 156 months in the CD38 bimodal expression group, regardless of the size of the CD38(+) population. The presence of a distinct CD38(+) population within the leukemic clone, rather than a numerical cutoff definition, correlates with IgV(H) gene mutational status and, irrespective of its size, identifies CLL patients who will have progressive disease.

ADP-ribosyl Cyclase↗
PubMed2002

Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22.

The natural history of B-chronic lymphocytic leukemia (CLL) is not entirely explained by intrinsic defects of the neoplastic cell, but is also favored by microenvironmental signals. As CLL cells retain the capacity to respond to CD40 ligand (CD40L) and as CD4(+) T cells are always present in involved tissues, we asked whether malignant CLL cells might produce T cell-attracting chemokines. We studied the chemokine expression of CD19(+)/CD5(+) malignant B cells from peripheral blood (PB), lymph nodes (LN) or bone marrow (BM) of 32 patients and found a major difference. LN- and BM-, but not PB-derived cells, expressed a readily detectable reverse transcription-PCR band for CCL22 and one for CCL17 of variable intensity. CD40 ligation of PB cells induced the mRNA expression of both CCL22 and CCL17. CCL22 was also released in the culture supernatants. These supernatants induced the migration of activated CD4(+), CD40L(+) T cells expressing the CCL22 receptor, CCR4. T cell migration was abrogated by anti-CCL22 antibodies. Immunohistochemistry and cytofluorography studies revealed that a proportion of CD4(+) T cells in CLL LN and BM expressed CD40L. Our data demonstrate that malignant CLL cells chemo-attract CD4(+) T cells that in turn induce a strong chemokine production by the leukemic clone, suggesting a vicious circle, leading to the progressive accumulation of the neoplastic cells.

Aged↗