Red cell alloimmunisation in patients with different types of infections

Abstract

Red cell alloantigen exposure can cause alloantibody-associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case-control study within a source population of patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Patients developing a first transfusion-induced red cell alloantibody (N = 505) were each compared with two similarly exposed, but non-alloimmunised controls (N = 1010) during a 5-week 'alloimmunisation risk period' using multivariate logistic regression analysis. Transfusions during 'severe' bacterial (tissue-invasive) infections were associated with increased risks of alloantibody development [adjusted relative risk (RR) 1·34, 95% confidence interval (95% CI) 0·97-1·85], especially when these infections were accompanied with long-standing fever (RR 3·06, 95% CI 1·57-5·96). Disseminated viral disorders demonstrated a trend towards increased risks (RR 2·41, 95% CI 0·89-6·53), in apparent contrast to a possible protection associated with Gram-negative bacteraemia (RR 0·58, 95% CI 0·13-1·14). 'Simple' bacterial infections, Gram-positive bacteraemia, fungal infections, maximum C-reactive protein values and leucocytosis were not associated with red cell alloimmunisation. These findings are consistent with murine models. Confirmatory research is needed before patients likely to develop alloantibodies may be identified based on their infectious conditions at time of transfusion.

A novel network analysis tool to identify relationships between disease states and risks for red blood cell alloimmunization

“…Notably, Evers et al . recently found that MDS was associated with a lower relative risk for alloimmunization, which contrasts with our findings. However, it is important to note that the association we observed was specifically among hyper‐responders (i.e.…”

“…b). The findings regarding sepsis in our study, which referred to patients categorized as having severe infections, are consistent with earlier studies , which indicated lower alloimmunization rates among patients with bacteraemia. It is unclear why the disorders in Fig.…”

“…Several reports suggest that select transfused patients (‘responders’ and ‘hyper‐responders’) may be more prone to developing alloantibodies . A potential contribution to antibody responsiveness is a patients underlying disease state – infectious diseases, haemoglobinopathies and neoplastic disorders have been associated with high alloimmunization rates . Collectively, these studies support the notion that disease status can be an important variable in alloimmunization.…”

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice

“…Multiple studies have established that certain inflammatory disorders and inflammatory stimuli increase the frequency and magnitude of alloimmune responses to RBC Ags (12–16, 19–21). However, the molecular mechanisms underlying these findings have not been previously studied.…”

“…Also, similar to prior murine studies, a recent human study reported that inflammation associated with different infections can have distinct effects. Patients with viremia were reported to have increased rates of alloimmunization, whereas patients with Gram-negative bacterial infections had lower rates (16). These associations indicate that specific pathways activated in some inflammatory conditions, such as autoimmunity and viral infections, promote RBC alloimmunization.…”