Current Protein and Peptide Science, Vol. 4, No. 4, 2003
Contents
Peptides
in the Diagnosis of Diseases
Guest
Editor: Sylviane Muller
Design of Synthetic Peptides for Diagnostics Pp.253-260
R.H. Meloen , W.C.
Puijk, J.P.M. Langeveld, J.P.M. Langedijk and P. Timmerman
Synthetic
Peptides in the Diagnosis of Systemic Autoimmune Diseases Pp.261-276
S. Fournel and S.
Muller
Synthetic
Peptides in the Diagnosis of Neurological Diseases Pp.277-284
F. Lolli , B.
Mazzanti , P. Rovero and A.M. Papini
Synthetic
Peptides in the Diagnosis of HIV Infection Pp.285-290
Maria Claudia Alcaro
, Elisa Peroni , Paolo Rovero and Anna
Maria Papini
GB
Virus C (GBV-C) / Hepatitis G Virus (HGV): Towards the Design of Synthetic
Peptides-based Biosensors for Immunodiagnosis of GBV-C/HGV Infection Pp.291-298
Nuria Rojo ,
Guadalupe Ercilla and Isabel Haro
Immunodiagnosis
of Parasitic Diseases with Synthetic Peptides Pp.299-308
O. Noya , M.E.
Patarroyo, F. Guzman and B. Alarcon de Noya
Abstracts
Back to top] Design of Synthetic Peptides for Diagnostics
R.H. Meloen , W.C.
Puijk, J.P.M. Langeveld, J.P.M. Langedijk and P. Timmerman
Due to the advantageous properties of synthetic molecules compared to biological ones biological molecules in diagnostic tests are replaced increasingly by synthetic ones, usually synthetic peptides or related molecules.
The replacement of biological antigens by synthetic peptides is most advanced at present, as well as the use of site-specific antibodies induced with synthetic peptides. Moreover recent results indicate that synthetic molecules may also replace antibodies. Ultimately this will lead to diagnostic assays built of synthetic molecules only.
Back to top] Synthetic
Peptides in the Diagnosis of Systemic Autoimmune Diseases
S. Fournel and S.
Muller
Proteins recognized by antibodies from patients with autoimmune diseases have been intensively studied over the two past decades since cDNAs encoding autoantigens have become available. Identity of many of them has been defined, and specific structural motifs or posttranslational modifications, which may be important to explain the generation of such antibodies during the autoimmune process, have been pointed out. Immunological analysis of sera from autoimmune patients with recombinant fragments and with short peptides has revealed the presence of dominant epitopes along proteins; some of them are targeted by antibodies from patients with specific diseases or disease subsets. Innovative technologies such as peptide arrays and biosensors as well as the exploitation of large peptides libraries have recently open up new perspectives. Peptides bearing natural modifications, peptide analogues, as well as mimotopes of protein or non-protein antigens (DNA, RNA, sugar) have been developed and might advantageously replace native antigens in routine immunoassays. Although numerous conformational epitopes have not yet been identified, and cannot be identified by the approaches classically used in epitope mapping studies, such peptides and peptide analogues may represent efficient probes to detect the presence of circulating autoantibodies in the serum of autoimmune patients and help for establishing specific and sensitive early diagnostic tests. They may also lead to the design of high-affinity ligands for purifying autoantibodies. These different aspects are discussed and epitope mapping studies of a number of autoantigens (e.g. histones, sn and hnRNP proteins and Ro proteins) are summarized.
Back to top]
Synthetic
Peptides in the Diagnosis of Neurological Diseases
F. Lolli , B.
Mazzanti , P. Rovero and A.M. Papini
For several years peptides have been used to investigate many aspects of the molecular mechanisms supporting the etiopathogenesis of neurological diseases. Even if well-established and commercially-available assays for the diagnosis of neurological diseases, based on peptides, are presently not available, much research has been focused to the comprehension of the pathogenetic mechanisms of relevant neurological diseases, such as Multiple Sclerosis, Alzheimer’s disease and prion diseases. Several peptides, which strongly contributed to increase in the progress, and in the understanding of the molecular mechanisms of these important diseases, have been selected as antigens to be proposed in possible alternative diagnostic methodologies. The authors focused their attention on the possible peptides to be used as diagnostics for these three characteristic neurological diseases. In fact, Multiple Sclerosis is an autoimmune disease in which peptides have been used for the characterization of both B and T immune response, while Alzheimer’s disease and prion diseases can be cumulative regarded as “protein folding disorders” in which peptides can be used to identify the misfolded protein.
Back to top] Synthetic Peptides
in the Diagnosis of HIV Infection
Maria Claudia Alcaro
, Elisa Peroni , Paolo Rovero and Anna
Maria Papini
Peptide-based enzyme-linked immunosorbent assays have been found to be enough sensitive and specific for the diagnosis of human immunodeficiency virus specific antibodies in acquired immunodeficiency syndrome patients. This review provides an overview of the most important peptides developed for use as synthetic antigens in immunodiagnosis of HIV-infected patients. In particular, many studies have been devoted to discriminate between the two retroviruses HIV-1 and HIV-2, as well as different subtypes.
Back to top]
GB Virus C
(GBV-C) / Hepatitis G Virus (HGV): Towards the Design of Synthetic
Peptides-based Biosensors for Immunodiagnosis of GBV-C/HGV Infection
Nuria Rojo ,
Guadalupe Ercilla and Isabel Haro
In the present study, new putative epitopes located in structural (E2) and non-structural (NS3) proteins of GBVC/ HGV were identified by computer-aided prediction of antigenicity and synthesized in solid-phase, following an Fmoc/tBut strategy, for their use in immunoassays. The corresponding synthetic peptides were used as antigens in ELISA assays and in real-time biospecific interaction measurements. This last approach allowed direct detection of GBVC/ HGV-specific antibodies in human sera. Good correlations were obtained between the biospecific interaction analysis and the ELISA.
To verify the performance of these new assays in comparison to the existing recombinant E2 protein commercial test, antibodies to synthetic peptides were searched for in different panels of serum samples. The main conclusion of this work is the usefulness of E2 peptides in the detection of antibodies. Moreover, the NS3 peptide could be exploited to improve the sensitivity of the currently available test.
Our results offer a new approach to develop new diagnostic peptide based biosensors for serodiagnosis of GBV-C/HGV infection.
Back
to top] Immunodiagnosis of Parasitic Diseases with
Synthetic Peptides
O. Noya , M.E.
Patarroyo, F. Guzman and B. Alarcon de Noya
Parasitic diseases remain as a major public health problem worldwide, not only based on their historically high morbidity and mortality rates, but also because risk factors associated with their transmission are increasing. Laboratory diagnosis and particularly immunodiagnosis is a basic tool for the demonstration, clinical management and control of these infections. Classically, the serological tests for the detection of antibodies or antigens are based on the use of crude and purified antigens. Synthetic peptides have opened a new field and perspectives, as the source of pure epitopes and molecules for diagnosis of malaria, Chagas´ disease, leishmaniasis, schistosomiasis, hidatidosis, cysticercosis and fasciolosis based on the detection of antibodies and circulating antigens. Herein, are critically reviewed the relevant advances and applications of the synthetic peptides on immunodiagnosis of parasitic diseases. A variety of sequences, constructs (monomers, polymers, MAPs), immunological methods and samples have been used, demonstrating their diagnostic potential. However, in most parasitic infections it is necessary to use more than a single peptide in order to avoid the genetic restriction against certain epitopes, as well as to test them in well characteized groups of patients, in order to confirm their sensitivity and specificity. The concept of multidiagnosis with synthetic peptides, using a novel multi-dot blot assay is introduced. Finally, the chemical imitation of antigens, offers a tremendous posibilities in the diagnosis of parasitic infections in developing countries since this strategy is cheaper, simpler, reproducible, useful for large scale testing and in most cases, specific and sensitive.