Isolation of scFv fragments to polymorphic and monomorphic HLA-DR epitopes from a synthetic phage library.

The possibility of producing human recombinant antibodies by the phage display libraries technology has opened up new perspectives in the fields of immunological research and therapeutic applications. Despite the interest for a potential use of this technology in the HLA field, no information is so far available about selection and screening of libraries with HLA antigens. In this study we report our first experience with expression and characterization of human single-chain antibody fragments (scFvs) against HLA-DR epitopes selected from a synthetic phage library.

A novel approach to human anti-HLA mABs production: use of phage display libraries.

The production of human monoclonal antibodies was previously limited to very laborious and time-consuming processes involving EBV-transformation and/or hybridoma generation. Due to the development of molecular cloning techniques, it is now possible to produce human monoclonal antibody fragments quickly by panning phage display libraries against predefined antigenic specificities. Therefore, we tested this technology for producing human single chain Fv fragments (scFvs) against HLA-DR1 purified molecules immobilized on solid phase. Enrichment of DR1-specific phages was measured through five selection rounds of a synthetic library and revealed a 100-fold amplification. Soluble antibody fragments were then expressed and 7 out of 48 clones were found to secrete scFvs which specifically bind to DR1 molecules in ELISA. Further analysis revealed binding of the scFvs also to DR3 but not to DR5 or DR7 molecules correlating with the presence of particular polymorphic aminoacid residues in the DR beta chain. Western blot analysis indicated that the 7 scFvs react with the DR1 alpha/beta-dimer but not with free alpha- or beta- chains. This study shows that the innovative approach of phage display libraries can efficiently provide scFv fragments as useful reagents for the identification and dissection of HLA polymorphic epitopes.

[Superficial disseminated porokeratosis with dermal amyloidosis]. / Porokératose disséminée superficielle avec amylose dermique.

A case of non-actinic disseminated superficial porokeratosis with dermal amyloid deposits in a 53 year-old-man is reported. The lesions of the trunk and arms were typical, but annular lesions of the ankles were lichenoid. The amyloid deposits were present under the cornoid lamella in the typical lesions and absent in the annular lesions. The different clinical variants of porokeratosis are discussed. The origin of amyloidosis is debated; it seems to be epidermic, due to degeneration of the keratinocytes. The secondary cutaneous amyloidosis is usually described in association with epithelial tumors or psoriasis, but exceptionally with porokeratosis.

[The carcinogenic role of earlier x-ray irradiation of multiple epitheliomas of the back. Critical study of 15 personal cases]. / Le rôle cancérigène des irradiations antérieures par rayons X dans les épithéliomatoses multiples du dos. Etude critique de 15 observations personnelles.

The authors report 15 cases of multiple epitheliomas of the back, concerning patients who had been previously submitted to X-ray irradiations. Their cases are divided into two groups: the first comprises 11 patients who had undergone lumbar and sacral anti-inflammatory radiotherapy for rheumatologic diseases; the second concerns 4 patients who had had many fluoroscopic examinations for lung tuberculosis and later developed multiple epitheliomas of the back. For each group of patients, they detail the irradiation procedures, and indicate the interval before the subsequent tumoral development, as well as the histologic features. In both groups, basal cell epitheliomas prevail with any type of histologic pattern (mainly pagetoid, however). Fibroepithelial tumours of Pinkus are not more numerous in the lumbar area (on the contrary: 20 p. 100 against 28.57 p. 100). Precancerous keratoses and Bowen-like conditions are only found in the second group (in fact in a single patient). The important feature is not the topography but the dose of irradiation. Fourteen out of 15 patients had only basal cell epitheliomas and fibroepithelial tumours.

[On five new cases of association of basal cell carcinoma and multiple Pinkus fibroepithelial tumors on the spine following radiation damage to the skin (author's transl)]. / A propos de cinq nouveaux cas d'épithéliomas baso-cellulaires et de tumeurs fibro-épithéliales de Pinkus multiples du dos sur des zones ayant antérieurement été traitées par radiothérapie.

The authors report five new cases associating basal cell epithelioma and multiple Pinkus fibro-epithelial tumors on the spine after radiation damage to the skin. One of them had previously published three similar observations: so his experience refers to eight cases. The authors recall similar cases of the literature, they discuss the relations between basal cell epitheliomas and Pinkus premalignant fibro-epithelial tumors of the skin. Histologically they saw several aspects of transition between the two types of tumors. They study the patterns of cancers found after radiation therapy, influence of type of radiations, dose, age, and intervals since X-rays. As regards such cases, the necessity of systematically searching for previous radiations by X-rays in the affected zone is emphasized.

[Erythrosis interfollicularis colli de Leder]. / L'erythrosis interfollicularis colli de leder

The authors have studied clinically and histologically two cases of " erythrosis interfollicularis colli de Leder ". It's a frequent affection, principally between 40 and 50 years of age but not very known because the patients rarely consult for it. Clinically they insist on the respect of a triangulary and lozengical median zone, and on the sight in "plucked chicken skin"; histologically on the dilatation of sebaceous glands, the frequency of a folliculary corneous plug and the elastic tissue alterations. On the etiological plan, the part of the age, the sun exposure, and in their two cases on the possible photosensibilisative part of the scents.