Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.

https://gut.bmj.com/content/gutjnl/62/1/43.full.pdf

The Oslo definitions for coeliac disease and related terms

A review of molecular recognition technologies for detection of biological threat agents.

In the year 2003 there was a 17% increase in the number of publications citing work performed using optical biosensor technology compared with the previous year. We collated the 962 total papers for 2003, identified the geographical regions where the work was performed, highlighted the instrument types on which it was carried out, and segregated the papers by biological system. In this overview, we spotlight 13 papers that should be on everyone's 'must read' list for 2003 and provide examples of how to identify and interpret high-quality biosensor data. Although we still find that the literature is replete with poorly performed experiments, over-interpreted results and a general lack of understanding of data analysis, we are optimistic that these shortcomings will be addressed as biosensor technology continues to mature.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmr.753

Survey of the year 2003 commercial optical biosensor literature

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(05)00047-8.pdf

Pharmaceuticals: a threat to drinking water?

qRT-PCR (real-time reverse transcription-PCR) has become the benchmark for the detection and quantification of RNA targets and is being utilized increasingly in novel clinical diagnostic assays. Quantitative results obtained by this technology are not only more informative than qualitative data, but simplify assay standardization and quality management. qRT-PCR assays are most established for the detection of viral load and therapy monitoring, and the development of SARS (severe acute respiratory syndrome)-associated coronavirus qRT-PCR assays provide a textbook example of the value of this technology for clinical diagnostics. The widespread use of qRT-PCR assays for diagnosis and the detection of disease-specific prognostic markers in leukaemia patients provide further examples of their usefulness. Their value for the detection of disease-associated mRNA expressed by circulating tumour cells in patients with solid malignancies is far less apparent, and the clinical significance of results obtained from such tests remains unclear. This is because of conceptual reservations as well as technical limitations that can interfere with the diagnostic specificity of qRT-PCR assays. Therefore, although it is evident that qRT-PCR assay has become a useful and important technology in the clinical diagnostic laboratory, it must be used appropriately and it is essential to be aware of its limitations if it is to fulfil its potential.

/pdf/real-time-reverse-transcription-pcr-qrt-pcr-and-its-4hkbllw6so.pdf

Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis.

Towards a new gliadin reference material-isolation and characterisation

OBJECTIVES: Antibodies that detect coeliac-toxic prolamins from wheat, barley and rye are important tools for controlling the diet of coeliac disease patients. Recently, a monoclonal antibody R5 that recognizes wheat gliadin, barley hordein and rye secalin equally was described. In this study, the epitope recognized by R5 was investigated. METHODS: Both a phage-displayed heptapeptide library and overlapping peptides spanning the sequence of alpha- and gamma-type gliadins (pepscan) were screened for binding of R5. RESULTS: Both techniques yielded comparable pentapeptide consensus sequences (phage display QXPW/FP; pepscan QQPFP). According to recent observations, this peptide stretch may be of key importance in the pathogenicity of coeliac disease. This sequence occurs repetitively in prolamins (in gamma- and omega-type prolamins more frequently than in alpha-type prolamins) together with several homologous peptide stretches, which are recognized less strongly. CONCLUSIONS: R5 seems to be a good candidate for the specific detection of putative coeliac disease-active sequences in prolamins and thus represents a valuable tool for the quality control of gluten-free food.

A monoclonal antibody that recognizes a potential coeliac-toxic repetitive pentapeptide epitope in gliadins.

A phage displayed dodecapeptide library and synthetic octapeptides spanning the complete sequence of α- and γ-type gliadin and overlapping in six amino acids (pepscan) were screened for binding to human gliadin antibodies (AGA). Phage display experiments led to four sequences recognized with significantly higher frequency by sera with raised IgA-AGA titres than by control sera. All these peptides contained the core sequence PEQ. Pepscan experiments revealed binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in α-type gliadin; and (v) QPQQPF (IgG and IgA) in γ-type gliadin. In two of the sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and QEQPFP, respectively, increased significantly binding of AGA from sera of patients with biopsy-proven or suspected coeliac disease (CoD), all positive for endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not enhanced by this substitution. Thus, AGA directed against these modified epitopes can be regarded as specific for CoD. This is the first study demonstrating that deamidation of gliadin improves reactivity of AGA of CoD patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2249.2000.01312.x

B cell epitopes of gliadin

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/S0014-5793%2897%2901201-5

Epitope mapping by screening of phage display libraries of a monoclonal antibody directed against the receptor binding domain of human α2‐macroglobulin

wasting marmoset syndrome ( WMS), characterized by failure to thrive, generalized weakness, often proBackground. Marmosets in captivity are highly susgressing to death [1‐3]. ceptible to wasting marmoset syndrome ( WMS ), the Chronic enteritis [4,5], diarrhoea [2], colon carcinaetiology of which is still not fully determined. oma [6 ], and glomerulopathy [7] with striking similarMethods. The level of IgA-gliadin antibodies (IgA- ities to IgA-nephropathy in humans [8] have been AGA), of IgA-containing circulating immune com- described in various members of the callitrichidae. The plexes (IgA-CIC ), and the degree of glomerular IgA diet of marmosets in captivity is considered as one deposits were compared between marmosets suVering possible cause for enteritis and WMS [4,9]. Recently, from WMS and animals not aVected by the disorder. a beneficial eVect of a gliadin-free diet on animals with Results. Both IgA-AGA and IgA-CIC were demon- WMS was reported [10]. strable in all groups of monkeys investigated. IgA- In susceptible humans, gliadins from wheat and AGA and IgA-CIC were significantly higher in mon- related proteins from other cereals represent the aetikeys with WMS than in non-aVected animals. There ological factor for coeliac disease [11,12] with damage was a significant correlation between the glomerular of the small intestinal mucosa, diarrhoea, increased IgA-deposition and titre of IgA-AGA. The group of anti-gliadin (AGA) and connective tissue antibodies marmosets strongly positive for glomerular IgA [13], and frequently enhanced circulating immune comdeposits comprised significantly more animals suVering plexes (CIC ) [14]. The antibodies involved include the from WMS than the group without deposits. In the IgA class. The incidence of glomerular IgA deposits diet of the animals a considerable amount of gliadin- in humans with coeliac disease is increased [15]. like cereal proteins was assayed. Furthermore, in man a relation between gliadins and Conclusions. There are several parallels between the primary IgA nephropathy is considered [16,17]. In this human disorders (coeliac disease and IgA-nephro- disorder, IgA is deposited in the glomerular mesangpathy/Bergeraes disease) and the changes observed in ium, which was found positive for food antigens in a WMS. It should be further investigated if WMS in significant fraction of patients [18], and frequently marmosets is a suitable animal model for both human IgA-CIC and antibodies against dietary antigens diseases.

Awad A. Osman

Papers

Towards a new gliadin reference material-isolation and characterisation

A monoclonal antibody that recognizes a potential coeliac-toxic repetitive pentapeptide epitope in gliadins.

B cell epitopes of gliadin

Epitope mapping by screening of phage display libraries of a monoclonal antibody directed against the receptor binding domain of human α2‐macroglobulin

IgA-Gliadin antibodies, IgA-containing circulating immune complexes, and IgA glomerular deposits in wasting marmoset syndrome