R. R. P. de Vries

TNF-308A and HLA–DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus

OBJECTIVEnTo evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE).nnnMETHODSnTNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes.nnnRESULTSnThe frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRBI*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation.nnnCONCLUSIONnTNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.

Progression of joint damage in early rheumatoid arthritis: Association with HLA–DRB1, rheumatoid factor, and anti–citrullinated protein antibodies in relation to different treatment strategies†

OBJECTIVEnTo determine the association of HLA-DRB1, rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) status with progression of joint damage in early rheumatoid arthritis (RA) treated according to different treatment strategies.nnnMETHODSnThe present study was conducted using data from the BeSt study (Behandelstrategieën voor Reumatoide Artritis [treatment strategies for rheumatoid arthritis]), a randomized trial comparing 4 targeted (toward achievement of a Disease Activity Score [DAS] of < or =2.4) treatment strategies: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with methotrexate, sulfasalazine, and prednisone (group 3), and initial combination therapy with methotrexate and infliximab (group 4), in 508 patients with early RA. Multivariate logistic regression analysis was used to predict progressive disease (increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [4.6]) according to the presence or absence of the shared epitope (SE), DERAA, RF, and ACPA, with correction for other baseline characteristics.nnnRESULTSnProgressive disease could not be predicted by presence of the SE: the odds ratio in groups 1, 2, 3, and 4, respectively, was 1.4, 2.6, 1.9, and 3.0. DERAA carriership did not protect against progressive disease (odds ratio 0.4, 1.4, 0.9, and 0.9 in groups 1, 2, 3, and 4, respectively). RF positivity and ACPA positivity predicted progressive disease in group 1 (odds ratio 4.7 [95% confidence interval 1.5-14.5] for RF and 12.6 [95% confidence interval 3.0-51.9] for ACPA), but not in groups 2-4 (for RF, odds ratio [95% confidence interval] 1.5 [0.5-4.9], 1.0 [0.3-3.3], and 1.4 [0.4-4.8] in group 2, group 3, and group 4, respectively; for ACPA, odds ratio [95% confidence interval] 3.4 [0.8-14.2], 1.7 [0.5-5.4], and 1.8 [0.5-6.8] in group 2, group 3, and group 4).nnnCONCLUSIONnIn patients with early RA treated with the goal of tight control of the DAS, no significant association between HLA-DRB1 status and radiographic progression was found. RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy. These observations suggest that effective treatment can prevent radiographic progression, even in patients with risk factors for severe damage.

Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart

Type 1 diabetes mellitus is a T-cell mediated autoimmune disease in which the insulin-producing pancreatic beta cells are selectively destroyed. Molecular mimicry and T-cell crossreactivity to beta-cell autoantigens and environmental agents with sequence similarities have been a proposed mechanism underlying the pathogenesis of type 1 diabetes, but actual crossreactivity has not yet been demonstrated. We isolated and investigated T cells reactive to GAD65 peptides and homologous peptides of the Coxsackie virus protein P2C and proinsulin from recent onset type 1 diabetes patients, and tested their fine specificity and cytokine production profile. Six T-cell lines specific for GAD65 peptides (amino acids 491-530) with homology to proinsulin (B20-C14) were isolated from six newly diagnosed patients with type 1 diabetes, but none of the stable T-cell lines crossreacted to the homologous proinsulin peptides. Similarly, none of four T-cell lines reactive to GAD65 peptides (amino acids 247-280) with sequence homology to Coxsackie P2C (amino acids 30-50) crossreacted to the homologous viral peptide. Two T-cell lines corecognized a GAD65 peptide and a Coxsackie P2C peptide. However, the antigen-specific T-cell clones from these T-cell lines were reacting either with the GAD65 peptide or the Coxsackie P2C peptide using different restriction elements without crossreacting to the homologous peptide. Our data demonstrate that homologous peptides previously proposed to serve as targets for crossreactivity indeed are immunogenic. Yet, T-cell clones did not crossreact with linear sequence homologies, despite strong T-cell responses to individual peptides.

Haemovigilance: an effective tool for improving transfusion practice

Haemovigilance is a tool to improve the quality of the blood transfusion chain, primarily focusing on safety. In this review we discuss the history and present state of this relatively new branch of transfusion medicine as well as some developments that we foresee in the near future. The top 10 results and conclusions are:

English translation of the Dutch Blood Transfusion guideline 2011.

The Dutch Blood Transfusion Guideline 2011 consists of recommendations for the blood transfusion practice and the underlying arguments for these recommendations. They were created through study of the literature and subsequent opinion forming within a multi-disciplinary working group with delegated representatives from the various professional organizations involved in blood transfusion. The aim of the 2011 revision was to update the multidisciplinary guideline on transfusion policy of blood and blood components from 2004 to promote the quality of blood transfusion and the skills of employees involved in it, with a focus on the hospital situation. The working method consisted of the evaluation of the relevance of research data published since 2003, subjects that were not discussed in the previous version and developments in the social debate, and incorporation of these matters into the new guideline. The recommendations were formulated to stimulate a more uniform clinical thinking and acting in the field of blood transfusion. A set of internal quality indicators based on the guideline has been developed, aimed at stimulating the effective and safe use of blood components. To improve the accessibility, a search function has been implemented from the table of contents in the PDF guideline document. When the reader clicks the cursor on the desired paragraph in the table of contents, he ⁄ she will be linked to the relevant paragraph. Amended and new recommendations compared to the previous version of the Blood Transfusion guideline have been marked in the text in turquoise and yellow, respectively. We have also used colours to mark a number of different sections, so that various types of users (paediatricians, nurses and laboratory employees) can find the sections relevant to them more easily. Since we made significant use of foreign guidelines (usually in English) in the creation of this guideline, we thought it would be a good idea to make our guideline accessible to foreign colleagues by translating the guideline into English. We are extremely grateful to the Sanquin Blood Supply Foundation for financing this translation. The English translation of the Dutch Blood Transfusion Guideline 2011 can be downloaded at http://www.sanquin. nl/en/products-services/blood-products/transfusion-guide line/ or http://www.diliguide.nl/document/7584. We hope that many foreign colleagues will enjoy reading this English translation of the Dutch Blood Transfusion guideline.

Haemovigilance: recent achievements and developments in the near future

Since the introduction of haemovigilance in the 1990s, the majority of the European countries has established a national haemovigilance system and communication between these systems was organized through the European Haemovigilance Network (EHN). The concept of haemovigilance has steadily expanded and the number of haemovigilance systems outside Europe is increasing. Several of these systems have also joined the EHN. Furthermore, initiated by the World Health Organization, a Global Steering Committee for Haemovigilance has been installed to promote haemovigilance particularly in developing countries. Both these haemovigilance systems and the network have documented the safety of blood transfusion and indicated where the main problems and opportunities for improvement are. Furthermore, they have suggested measures for improvement of the safety and, last but not least, documented the effect of these measures. Therefore, they have contributed considerably to the improvement of the quality and safety of the blood transfusion chain. In the near future, the EHN will become an official International Haemovigilance Network. Ongoing developments concerning the scope of vigilance include the vigilance of optimal use of blood products and safety of cells and tissues of human origin (biovigilance).