Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (α1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low α1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease

Comparative analysis of the prices of essential medicines among Bulgaria and Macedonia

The prices of medicines differ because of many reasons as the sector that is purchasing medicines, distribution channel, patent status, trade mark and methodology of pricing. The current study aims at comparing the manufactoring, wholesale and retail prices of 30 30 INN essential medicines in Bulgaria and Macedonia as well their affordability to the population. There are presented the results for amoxicillin and glibenclamid. The collection, verification and data analysis are following the new WHO approach for medicines prices comparison. For the 30 INN included in the WHO list are collected data for registered trade marks in both countries, and their prices are collected. The randomized sample of 4 regions in both countries were created at whole - sale and retail prices are observed for the selected INN. It is compared the prices of generic and branded products for each segment - manufactoring, wholesale and retail. The affordability of the population to the medicines necessary for the treatment of diabetes II and bronchopneumonia is calculated comparing the cost of monthly treatment and minimal governmental wages in both countries. The analysis of the ceiling prices calculated by the MoH in Bulgaria revealed that in order to increase affordability is necessary to negotiate prices mainly at manufactoring level. It is also necessary to consider the discounts that are provided within ceiling prices that made prices lower at consumer level and also change the price structure. The analysis show that the prices in both countries differ in significant extend but the existing price control mechanisms are effective and allow pepople affordability to important medicines

Isolation and partial characterization of Fes p 4 allergen

More than 75% of grass pollen-allergic patients produce specific IgE antibodies against group-4 allergens. Purification and characterization of different grass group-4 allergens should help to further understand their allergenicity. In this study, an attempt was made to isolate and characterize Fes p 4 allergen by several biochemical and immunochemical methods. Fes p 4 was purified by a combination of chromatographic techniques (gel permeation and ion exchange chromatography). Isolated protein revealed four main spots at a molecular weight of 60 kDa and a pi ranging from 8.7 to 9.1. Eight sera were selected from patients with positive result of skin prick test to the mixture of grass pollen extracts. ELISA inhibition technique was used to study Fes p 4-specific IgE in the patients' sera. ELISA to Festuca pratensis was inhibited up to 80% by F. pratensis pollen extract and up to 48% by Fes p 4. 2D-PAGE-immunoblot was used to identify allergenic and antigenic components of Fes p 4 with patients' IgE and monoclonal antibodies (MABs). Three components of purified protein expressed IgE binding ability. Two MABs which recognized unrelated regions on Phl p 4 bound three components of Fes p 4. The role of the carbohydrate moiety in allergenicity was examined with individual patient sera by using periodate-treated Fes p 4. Six out of eight patients reduced IgE binding to periodate-treated allergen. Isolated Fes p 4 glycoprotein consisted of four components, three of which were allergenic, and share common epitopes specific for grass group-4 homologs. The results of periodate oxidation of Fes p 4 suggest that the carbohydrate moiety is involved in IgE binding