title: A nonparametric procedure for defining a new humoral immunologic profile in a pilot study on HIV infected patients.
abstract: This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to "feasibility" studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical profiles strongly rely on functional activity against HIV.
authors.affiliation: Centro Universitario di Statistica per le Scienze Biomediche, University Centre of Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Brombin
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Diomede
authors.forename: Daniela
authors.initials: D
authors.lastname: Tudor
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Drillet
authors.forename: Claudia
authors.initials: C
authors.lastname: Pastori
authors.forename: Elena
authors.initials: E
authors.lastname: Poli
authors.forename: Agostino
authors.initials: A
authors.lastname: Riva
authors.forename: Caterina
authors.initials: C
authors.lastname: Uberti-Foppa
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Clelia
authors.initials: C
authors.lastname: Di Serio
authors.forename: Morgane
authors.initials: M
authors.lastname: Bomsel
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007070:Immunoglobulin A; D007074:Immunoglobulin G