Infliximab-induced lupus-like reaction in a patient with psoriatic arthritis.
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Antibodies, Monoclonal↗
Biomedical subjects
P Puddu
Publications and source records attributed to P Puddu.
Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".
The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.
Age of Onset↗
Alpha4beta1 and alpha4beta7 CD4 T cell numbers increase and CLA CD4 T cell numbers decrease in systemic sclerosis.
We studied the expression of adhesion molecules affecting recirculation and homing on peripheral blood CD4(+) T cells of patients with systemic sclerosis (SSc), in order to evaluate whether the distribution of tissue targeted subsets could reflect the participation of internal organs or the extent of cutaneous involvement [i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age-matched controls were investigated by cytofluorimetric analysis for lymphocyte subpopulations carrying the following surface molecules: CD3, CD4, CLA, alpha4beta7 and alpha4beta1. Standard routine biochemistry and clinical examinations were also performed in all patients. We found that both alpha4beta1(+) and alpha4beta7(+) cells within the CD4(+) T cell population were significantly increased, while CLA(+) CD4(+) T cells were significantly reduced in SSc, compared to healthy donors. Significantly lower absolute numbers of alpha4beta7(+) cells were found in lc- compared to dc-SSc. Patients with oesophageal involvement had high numbers of alpha4beta7(+) cells, while those with nephritis also showed low levels of CLA(+) cells. Lung involvement was related directly to alpha4beta1(+) cell numbers and inversely to alpha4beta7(+) CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4(+) T cell populations with selective homing properties show changes from normal distribution in SSc, and such changes are related to clinical expression and organ involvement in the course of the disease.
Adult↗
Genes and atherosclerosis: at the origin of the predisposition.
Atherosclerosis (ATS) is a multifactorial disease caused by the interaction of established or emerging risk factors with multiple predisposing genes that regulate ATS-related processes. This review will discuss the current knowledge concerning the potential role of the genetic variations that could promote and/or accelerate ATS, in both animal models and humans. Allelic polymorphisms or variations of distinct genes that enhance the risk of ATS frequently occur in the general population, but only adequate gene-environment interactions will lead to the disease. The main genes so far studied are involved in the regulation of processes such as endothelial function, antioxidant potential, coagulation, inflammatory response, and lipid, protein and carbohydrate metabolism. The detection of candidate genes associated with ATS could allow, in the near future, earlier interventions in genetically susceptible individuals. Further, large-scale population studies are needed to obtain more information on the specific gene-environment and drug-gene interactions capable of influencing ATS progression.
ATP Binding Cassette Transporter 1↗
Burnout and job satisfaction comparing healthcare staff of a dermatological hospital and a general hospital.
BACKGROUND: Psychological distress among healthcare professionals can have negative effects on the well-being of the professionals and also on the quality of care they provide to patients. OBJECTIVES: To evaluate burnout and job satisfaction of dermatologists and nurses working with dermatological patients compared with physicians and nurses of other specialties. METHODS: A self-completed anonymous questionnaire was distributed to the personnel of two hospitals in Rome, Italy: a dermatological hospital (IDI) and a general hospital (GH), belonging to the same non-profit organization. Standardized instruments were used to assess burnout (Maslach Burnout Inventory) and job satisfaction. Multiple logistic regression was used to examine the association between burnout and working in dermatology vs. other specialties, job satisfaction, years of employment and respondents' sex and age. RESULTS: We distributed 929 questionnaires to clinical and non-clinical staff of IDI and 494 questionnaires to the GH staff (response rates: 53% at IDI and 50% at the GH). Among respondents there were 67 physicians and 59 nurses at IDI and 70 physicians and 148 nurses at the GH. Subsequent analyses refer only to this clinical subsample. Factor analysis showed that among physicians and nurses the two main factors explaining job satisfaction were respondents 'satisfaction with the management of their unit' and 'opportunities for personal growth'. Among nurses the likelihood of burnout decreased significantly with higher levels of job satisfaction [odds ratio (OR) = 0.78; 95% confidence interval (95% CI) 0.7-0.9] and working in dermatology compared with other specialties (OR = 0.46; 95% CI 0.2-0.9). Among physicians a lower likelihood of burnout was associated with job satisfaction (OR = 0.66; 95% CI 0.5-0.8) and older age (OR = 0.28; 95% CI 0.1-0.8). CONCLUSIONS: Among both physicians and nurses, job satisfaction was associated with a lower likelihood of burnout, independently of clinical specialty and other factors. Burnout was similar for dermatologists and other specialists. Nurses of the GH compared with those working in dermatology had a higher probability of burnout and were significantly less satisfied with the management of their units and with opportunities for personal growth.
Adult↗
Effects of patient satisfaction with care on health-related quality of life: a prospective study.
OBJECTIVES: To evaluate the effect of patient satisfaction on health-related quality of life among dermatological outpatients, independently of patients' sociodemographic, and clinical characteristics. DESIGN: Prospective cohort study. Satisfaction was evaluated with a standardized questionnaire three days after the visit by telephone interview. Quality of life and psychiatric disorders were measured with validated instruments (Skindex-29 and Ghq-12) before the dermatological visit and after four weeks. At the four week interview also self-reported medication adherence was assessed. SETTING: Outpatient clinics of a large dermatological hospital in Rome, Italy. PATIENTS: A consecutive sample of 1389 outpatients was approached, and 52% agreed to participate. Inclusion criteria were met by 424 patients, and 396 (93%) of them completed the study. MAIN OUTCOME MEASURES: Improvement in health related quality of life. RESULTS: At multivariate analysis satisfied patients have approximately twice the odds for an improved quality of life on the emotions scale (OR = 1.99; 95%CI 1.1 to 3.7; P = 0.03) and on the functioning scale (OR = 2.2; 95%CI 1.1 to 4.7; P = 0.03). Patients with psychiatric disorders at baseline were less likely to have an improved quality of life on the functioning scale (OR = 0.3; 95%CI 0.2 to 0.8; P = 0.01). CONCLUSIONS: This is the first prospective study showing that patient satisfaction and psychiatric disorders have a significant effect on quality of life improvement among dermatological patients, independently of patient characteristics. Particular attention should be devoted to improving physicians' interpersonal skills, the major component of patient satisfaction.
Adolescent↗
Study on the frequency of protozoa and mycetes in the oral cavity.
The importance of a good knowledge in microbiology of the oral cavity is every day more and more indispensable in order to propose proper therapeutic treatments. In this study, the most frequent protozoa and mycetes present in the oral cavity are described, distinguishing the different species and their pathologies.
Animals↗
Amelanotic/hypomelanotic melanoma: clinical and dermoscopic features.
BACKGROUND: Amelanotic malignant melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. It may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions. OBJECTIVES: To evaluate whether dermoscopy is also a useful technique for the diagnosis of amelanotic/hypomelanotic melanoma (AHM). METHODS: We conducted a retrospective clinical study of 151 amelanotic/hypomelanotic skin lesions from 151 patients with a mean age of 47 years (+/- 17.5 SD). Digitized images of amelanotic/hypomelanotic skin lesions were converted to JPEG format and sent by e-mail from the five participating centres. Lesions included 55 amelanotic/hypomelanotic nonmelanocytic lesions (AHNML), 52 amelanotic/hypomelanotic benign melanocytic lesions (AHBML), and 44 AHM, 10 (23%) of which were nonpigmented, truly amelanotic melanomas (AM). The 44 AHM lesions were divided into thin melanomas (TnM) </= 1 mm (29 cases) and thick melanomas (TkM) > 1 mm (15 cases), according to the Breslow index. Five clinical features (elevation, ulceration, shape, borders and colour) as well as 10 dermoscopic criteria (pigment network, pigmentation, streaks, dots/globules, blue-whitish veil, regression structures, hypopigmentation, leaf-like areas, multiple grey-bluish globules, central white patch) and eight vascular patterns (comma, arborizing, hairpin, dotted, linear irregular, dotted and linear irregular vessels, and milky-red areas) were evaluated in order to achieve clinical and dermoscopic diagnoses. Statistical analyses were performed with the chi2-test and Fisher's exact test, when appropriate. RESULTS: The most frequent and significant clinical features for TnM and TkM were asymmetry and ulceration (the latter only for TkM) compared with AHBML. Irregular dots/globules (62% vs. 35%; P </= 0.03), regression structures (48% vs. 27%; P </= 0.03), irregular pigmentation (41% vs. 11%; P </= 0.03) and blue-whitish veil (10% vs. 0%; P </= 0.03) were the most relevant dermoscopic criteria for TnM in comparison with AHBML. TkM differed significantly from AHBML in frequency of occurrence of irregular pigmentation (87% vs. 11%; P </= 0.03), irregular dots/globules (73% vs. 35%; P </= 0.03), regression structures (67% vs. 27%; P </= 0.03), blue-whitish veil (27% vs. 0%; P </= 0.03) and hypopigmentation (13% vs. 55%; P </= 0.03). Linear irregular vessels and the combination of dotted and linear irregular vessels associated with TnM and TkM were not found in our cases of AHBML and were only rarely seen in AHNML (3.6% and 1.8%, respectively). Moreover, TkM differed significantly from AHBML and TnM in frequency of occurrence of milky-red areas (93% vs. 17%; P </= 0.03 and 93% vs. 31%; P </= 0.01, respectively). The dermoscopic diagnosis of melanoma had a higher sensitivity and specificity than the clinical diagnosis (89% and 96% vs. 65% and 88%, respectively). With the limitation of the small number of cases, vascular patterns were the only dermoscopic criteria for 'truly' AM. In the 10 cases of 'truly' AM, we found milky-red areas in more than half of the cases (six of 10), dotted vessels in four, hairpin vessels in two, linear irregular vessels in two, dotted and linear irregular vessels in two. CONCLUSIONS: Because dermoscopy uses criteria reflecting pigmentation (irregular pigmentation and irregular dots/globules) and vascular patterns, it is a useful technique not only for pigmented melanoma but also for hypomelanotic melanoma. In 'truly' AM, vascular patterns alone may not be sufficient to diagnose melanoma. A combined approach with the clinical information should help in the detection of 'truly' AM.
Adult↗
Interleukin-16 expression and release in bullous pemphigoid.
Cutaneous infiltration of activated CD4(+) T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4(+) cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4(+) T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP.
Acute Disease↗
Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement.
Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-gamma (IFN-gamma ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-beta1, Tumour necrosis factor (TNF)-alpha, sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1alpha and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNFalpha and MCP-1 but reduced amounts of gamma-IFN and MDC. IL6, IL10, IL18, MIP-1alpha and TNFalpha measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-beta1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.
Cell Line↗
Distinct delayed T-cell response to beta-methasone and penicillin-G in the same patient.
BACKGROUND: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs. Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome. Our aim was to report the case of a delayed reaction to both beta-methasone (beta-MT) and penicillin-G (pen-G) occurring in the same patient, and analyse beta-MT- and pen-G-specific T-cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile. METHODS: We generated two drug-specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T-cell receptor Vbeta (TCR-Vbeta) domains expression and cytokine profile. RESULTS: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen-G and beta-MT through the strict dose-dependent proliferation in response to drug-pulsed autologous antigen presenting cells. Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with beta-MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen-G was found. The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR-Vbeta usage. CD8+ pen-G-TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific beta-MT TCL. CONCLUSION: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and beta-MT, driven, respectively, by pen-G-specificTh2-skewed CD8+ and beta-MT specificTh0 CD4+ T cells. This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity.
Adult↗
Novel and recurrent mutations in the integrin beta 4 subunit gene causing lethal junctional epidermolysis bullosa with pyloric atresia.
In this study we examined two unrelated patients affected with the lethal variant of junctional epidermolysis bullosa with pyloric atresia (PA-JEB) who were found to carry mutations in the integrin beta4 subunit gene (ITGB4). Although in both patients Northern blot analysis showed only a 50% reduction in the level of ITGB4 transcript, a complete lack (patient 1) or a strong reduction (patient 2) of beta4 immunoreactivity was observed in the skin. Using immunoprecipitation analysis, integrin beta4 could not be visualized in patient 1 cells while a markedly reduced amount (approximately 20%) of normal sized beta4 chains was detected in patient 2. These data suggested the presence of ITGB4 mutations that interfere with both mRNA and protein stability. Using molecular analysis, patient 1 was shown to be a compound heterozygous for a single amino acid deletion (deltaN318) and a not yet identified mutation that induces a very rapid decay of the encoded mRNA transcript. Patient 2 was, instead, a compound heterozygous for a novel 4-bp tandem duplication (4298-4299ins4) and a previously described missense mutation (R252C). Our data support the notion that PA-JEB lethal phenotypes associated with a markedly decreased/absent alpha6beta4 expression can be due not only to the presence of null alleles, but also to specific mutations leading to protein instability and/or altered function.
Epidermolysis Bullosa↗
A comparison of acute phase proteins and traditional risk factors as markers of combined plaque and intima-media thickness and plaque density in carotid and femoral arteries.
OBJECTIVES: To test the hypothesis that some acute phase proteins may be better independent predictors of objective measures of arterial wall impairment than traditional risk factors. DESIGN: Cross-sectional study. MATERIALS AND METHODS: C-reactive protein (CRP), fibrinogen, C3 complement and traditional risk factors were measured in 288 men aged 55-64 years, randomly chosen from the local registry lists. By ultrasound assessment of the bifurcations of carotid and femoral arteries, maximum combined plaque/intima-media thickness (CPIMTmax) and mean plaque density (MPD, in a grey scale from 0 to 255) were also measured. RESULTS: In multivariate analysis only traditional risk factors remained associated with the overall CPIMTmax: smoking (r = 0.35, p < 0.0001), cholesterol (r = 0.23, p = 0.0001), age (r = 0.22, p = 0.0002), glucose (r = 0.18, p = 0.002) and systolic blood pressure (r = 0.13, p = 0.02). However, with regard to carotid disease only, fibrinogen was the strongest covariate of CPIMT (r = 0.18, p = 0.002). The overall MPD was independently associated with CRP (r = 0.25, p = 0.0008), physical activity (r = 0.19, p = 0.009), triglycerides (r = -0.18, p = 0.02) and body mass index (r = 0.15, p = 0.04). CRP was mainly associated with femoral MPD, while triglycerides were the major (inverse) covariate of carotid MPD. CONCLUSIONS: Traditional risk factors are the main determinants of CPIMTmax, although fibrinogen seems to play a role in carotids. CRP was associated with high density femoral plaques. Finally, no acute phase protein was independently associated with low density, potentially vulnerable, plaques.
Acute-Phase Proteins↗
Different associations of C-reactive protein, fibrinogen and C3 with traditional risk factors in middle-aged men.
BACKGROUND: Some acute phase proteins are associated with both ischemic events and traditional risk factors. Since they are strongly interrelated, each of them partly reflects the characteristics of other proteins. This study was carried out to ascertain the specific preferential associations of some acute phase proteins with traditional risk factors for atherosclerotic disease. METHODS: High-sensitivity C-reactive protein, fibrinogen and C3-complement were assessed in 288 unselected men aged 55-64 years. Three multiple linear regression analyses were performed, in which each of the three acute phase proteins was considered the dependent variable of both traditional risk factors and the other two proteins. RESULTS: The three acute phase proteins strongly correlated with each other. Moreover, C-reactive protein was independently associated with triglycerides (P<0.0001), age (P=0.0130), body mass index (P=0.0179), and acute (P=0.0280) and chronic (P=0.0582) inflammations (R2=0.17). Fibrinogen was associated with alcohol consumption (inversely, P=0.0001) and smoking (P=0.0598) (R2=0.06). Finally, C3 was associated with insulin (P<0.0001), cholesterol (P=0.0001), sedentarity (P=0.0028), glucose (P=0.0077), and systolic blood pressure (P=0.0124) (R2=0.28). CONCLUSIONS: When simultaneously studied in multivariate analysis, acute phase proteins have different preferential associations with traditional risk factors, a probable consequence of their involvement in different cellular activations and metabolic processes.
Age Factors↗
[Sentinel node biopsy for malignant melanoma. Technical details and clinical results on 390 patients].
BACKGROUND: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed. METHODS: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done. RESULTS: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm. CONCLUSIONS: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.
Biopsy↗
Lessons from the "Euro-Lupus Cohort".
The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.
Adolescent↗
Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life.
OBJECTIVE: To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy. DESIGN: Hospital-based case-control study. SETTING: A referral dermatological hospital in Rome, Italy. PATIENTS: A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997. RESULTS: In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P =.01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC. CONCLUSION: The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.
Adolescent↗
Identification of a LFA-1 region involved in the HIV-1-induced syncytia formation through phage-display technology.
We have identified a peptide region on CD18 molecule (the beta subunit of the LFA-1 molecule) involved in syncytia formation of HIV-1-infected lymphocytes. Several phage clones mimicking an epitope of the CD18 cell-surface determinant were isolated from two 9-mer random peptide phage-displayed libraries via their binding to the CD18-specific monoclonal antibody (mAb) MHM23, which in in vitro assay inhibits syncytia formation in HIV-1-infected cells. The peptide sequences displayed on phages that blocked immunolabeling of this mAb on LFA-1-expressing cells were used to identify the epitope recognized by mAb MHM23 by sequence comparison. On the basis of this analysis, two peptides which inhibited syncytia formation in HIV-1-infected cells in vitro were synthesized, thus confirming that they mimic a CD18 domain that is involved in this phenomenon. The results here presented highlight the potential of phage-display technology for the study of biological processes at the basis of virus infection, but also suggest new approaches for the therapy of AIDS.
Animals↗