DIARECT Newsletter July 2018
Dear Madam or Sir,
The AACC Annual Scientific Meeting and Clinical Lab Expo is the world's premier gathering for laboratory medicine. This year 20,000 laboratory scientists from a broad range of specialties are expected to attend. You will have the opportunity to connect with global leaders in clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management and buyers of your in vitro diagnostic products. With more than 200 educational and scientific sessions, you keep pace with changes in the field.
The 70th AACC Annual Scientific Meeting and Clinical Lab Expo will take place in Chicago from July 29 – August 2, 2018. To learn more about the event click here.
DIARECT will be attending and would like to invite you to stop by our booth #3035. It is our pleasure to meet up with business partners, customers and potential new clients.
This issue of our Newsletter gives you a first impression and description of the newest additions to DIARECT’s extensive product portfolio. To get an overview of all our products, including the antigens to be presented at this year’s AACC, have a look at our new product list, available at this link: product list
If you wish to personally meet with a member of the DIARECT team at the Clinical Lab Expo or are interested in receiving more information, please feel free to contact us at:
Tel. +49 761 47979-0
We are looking forward to seeing you in Chicago!
Completing the Anaplasma portfolio: Anaplasma phagocytophilum OmpA
Human Granulocytic Anaplasmosis (HGA) was first recognized in the United States and is the most common tick-borne disease after Borreliosis. It is endemic in 42 countries with an overall case fatality of 5%. The causative agent of HGA is the rickettsial species Anaplasma phagocytophilum, a Gram-negative obligate intracellular pathogen infecting mammalian hosts worldwide. It invades and replicates within neutrophils by employing an array of mechanisms to subvert their bactericidal activity. Characteristic is the development of intracytoplasmic morulae within those peripheral blood granulocytes. Several epitopes on surface proteins of Anaplasma phagocytophilum are targeted during an immune response.
Major outer membrane protein A (OmpA) of A. phagocytophilum is a peptidoglycan-binding lipoprotein, transcriptionally upregulated during tick transmission feeding and playing an important role in the pathogenesis of HGA. The integral outer membrane channel belongs to the porin superfamily, which share a beta-barrel structure.
The invasion domain of OmpA is conserved in all Anaplasma and Ehrlichia species. Invasion is mediated by interaction of the protein with α2,3-sialic acid of the sialyl Lewis x (sLex) tetrasaccharide, which caps P-selectin glycoprotein ligand-1 (PSGL-1) and other glycoproteins on eukaryotic cell surfaces. Binding of the bacterium to these receptors on the membrane promotes endocytosis. Therefore, the invasin OmpA, together with other proteins, is important for entry into mammalian cells and critical for infection of neutrophils in host cells. Using an agonist for OmpA receptors, e.g. glutathione S-transferase (GST)–OmpA, shows that A. phagocytophilum infection of host cells is reduced by approximately 50 % as it blocks access of native OmpA on the bacterial surface to sialic acids.
Until now, DIARECT has provided the immunodominant major surface protein 5 (Msp5), also present in the salivary glands of infected ticks, and A. phagocytophilum p44, a transmembrane protein of the outer membrane, which is thought to enable the bacterium to avoid host immune surveillance. To complete the Anaplasma product line, DIARECT is now offering a third A. phagocytophilum antigen produced in E.coli to expand this product line: OmpA. All three proteins are considered main antigens of antibody response to HGA.
Atifi et al. (2015) Parasitol Res. DOI 10.1007/s00436-015-4698-2
Blanco and Oteo (2002) Clin Microbiol and Infect. 8: 763–772
Chen et al. (1994) J Clin Microbiol. 32:589–595
Ijdo et al. (1998) Infect Immun. 66: 3264–3269
Kahlon et al. (2013) Infect Immun. 81:65-79
Knowles et al. (1996) J Clin Microbiol. 34: 2225-2230
Lotric-Furlan et al. (1998) Clin Infect Dis. 27: 424–428
Ojogun et al. (2012) Infect Immun. 80: 3748–3760
Palmer et al. (1994) J Clin Microbiol. 42:5381–5384
Park et al. (2003) Infect Immun. 71: 4018–4025
Rikihisa et al. (2007) Journal Bacteriol. 189: 7819–7828
Wang et al. (2013) PLoS One. 8 (10): e78189
For additional product related information please feel free to contact us at:
Tel: +49 761 47979-0
New Humanized Monoclonal Antibodies: PCNA humAb IgG and Mi-2 humAb IgG
The nucleosome remodeling deacetylase (NuRD) complex exerts histone deacetylase activity and functions in the regulation of gene transcription. Mi-2 protein, a subunit of the NuRD complex, is a DNA-dependent ATPase helicase and appears to be involved in the repair of the basal epidermis.
Mi-2 autoantibodies are considered specific serological markers of dermatomyositis, an idiopathic myopathy characterized by the presence of inflammatory infiltrates within skeletal muscle. Together with adult polymyositis, dermatomyositis is one of the most common subtypes of these idiopathic myopathies along with inclusion body myositis, childhood myositis, malignancy-associated myositis, and myositis in overlap with mixed connective tissue disease.
Proliferating cell nuclear antigen (PCNA; syn. Cyclin), a co-factor of DNA polymerase delta, forms homotrimers around double stranded DNA, and is involved in DNA replication and repair. Since its expression rate correlates with the rate of DNA replication, PCNA is a proliferation marker in basic research.
Systemic lupus erythematosus (SLE) is a debilitating, chronic, life-threatening, systemic autoimmune disease that can affect virtually any organ. The course of SLE varies from mild episodic illness to a fatally severe disease.
PCNA autoantibodies have been reported to be serological markers of SLE, together with other antibodies, and recognize specific conformational epitopes. In particular they are present in those patients suffering from arthritis and hypocomplementemia, and drop below detection limits following drug treatment.
Immunoassays for the detection of antibodies in patient samples require reference material to determine cut-off values and test assay integrity, and these are then included in the kit as calibrators or positive controls. One of the latest advances in assay development are chimeric monoclonal antibodies as an alternative to characterized disease state plasma, which are limited in availability, show variability, and there are also safety and ethical issues. Two years ago, DIARECT introduced the first human chimeric monoclonal antibodies of this new product line.
These antibodies are produced in transgenic mouse strains in which the sequence for mouse IgG1 Fc region is substituted with the human sequence. After mouse immunization and hybridoma technology, antibodies are generated that retain a human constant region required for recognition by the anti-human conjugate.
DIARECT currently provides tissue-specific chimeric antibodies for the detection and diagnosis of autoimmune liver diseases and SRP54 humAb IgG for myositis. DIARECT is further expanding this product line with the introduction of Mi-2 humAb IgG and PCNA humAb IgG. Additional new products related to autoimmune liver and systemic autoimmune diseases will follow shortly.
Betteridge ZE et al. (2011) Arthritis Research & Therapy. 13:209-215
Hoshino K et al. (2010) Rheumatology. 49:1726-1733
Cogné et al. (2013) European Patent N°13305964.2
Invernizzi et al. (2008) World J Gastroenterol. 21:3374-3387
Arbuckle et al. (2003) N Engl J Med. 349:1526-1533
Brand et al. (1994) J Immunol. 152:4120-4128
Cozzani et al. (2014) Autoimmune Dis. 2014:321359
Eriksson et al. (2011) Arthritis Res Ther. 13:R30
Heinlen et al. (2010) PloS One. 10:e9599
Heinlen et al. (2010) J Mol Med (Berl). 88:719-727
Mahler et al. (2010) Lupus. 19:1527-1533
Miyachi et al. (1978) J Immunol. 121:2228-2234
Sherer et al. (2004) Semin Arthritis Rheum. 34:501-537
For questions or additional information please feel free to contact us at:
Tel: +49 761 47979-0
To facilitate the world-wide sales of our antigens, DIARECT has distribution agreements with select companies.