Human platelet antigens – 2013

To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA‐1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic ‘systems’ where the –a form designates the higher frequency allele and the –b form, the lower. Twenty‐one other HPAs are low‐frequency or rare antigens for which postulated higher frequency –a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR.     

Krankenhausfinanzierung 2013

Hospital financing is again subjected to a multitude of reforms that can be of relevance for rheumatology in 2013. Besides changes in the German diagnosis-related group (G-DRG) classification system and coding, modifications in the legislation and legal framework conditions have a growing impact on the economic situation and strategy of hospitals. The following article presents the major changes and discusses consequences for hospitals specialized in rheumatology.     

Heart failure highlights in 2012–2013

Heart failure has become the cardiovascular epidemic of the century. The European Journal of Heart Failure is dedicated to the advancement of knowledge in the field of heart failure management. In 2012 and 2013, several pioneering scientific discoveries and paradigm‐shifting clinical trials have been published. In the current paper, we will discuss the most significant novel insights into the pathophysiology, diagnosis, and treatment of heart failure that were published during this period. All relevant research areas are discussed, including pathophysiology, co‐morbidities, arrhythmias, biomarkers, clinical trials, and device therapy, including left ventricular assist devices.     

Quantitative heritability of anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis

Objective

The majority of genetic risk factors for rheumatoid arthritis (RA) are associated with anti–citrullinated protein antibody (ACPA)–positive RA, while far fewer genetic risk factors have been identified for ACPA‐negative RA. This study was undertaken to quantify the contribution of genetic risk factors in general, and of the predisposing HLA–DRB1 shared epitope (SE) alleles in particular, to the ACPA‐positive and ACPA‐negative subsets of RA, by computing their heritability and assessing the contribution of the HLA SE alleles.

Methods

One hundred forty‐eight RA twin pairs, in which at least 1 twin of each pair had RA, were tested for ACPAs and typed for HLA–DRB1 genotypes. Heritability was assessed in a logistic regression model including a bivariate, normally distributed random effect, representing the contribution of unobserved genetic factors to RA susceptibility, with the correlation of the random effects fixed according to twin zygosity. The contribution of the HLA SE alleles to genetic variance was assessed using a similar model, except that estimates were based on genotype‐specific population prevalences.

Results

The heritability of RA among the twin pairs was 66% (95% confidence interval [95% CI] 44–75%). For ACPA‐positive RA, the heritability was 68% (95% CI 55–79%), and for ACPA‐negative RA it was 66% (95% CI 21–82%). Presence of the HLA SE alleles explained 18% (95% CI 16–19%) of the genetic variance of ACPA‐positive RA but only 2.4% (95% CI 1.6–10%) of the genetic variance of ACPA‐negative RA.

Conclusion

The heritability of ACPA‐positive RA is comparable with that of ACPA‐negative RA. These data indicate that genetic predisposition plays an important role in the pathogenesis of ACPA‐negative RA, for which most individual genetic risk factors remain to be identified.