Chronic Inflammatory Autoimmune Disorders Are a Risk Factor for Blood Group Alloimmunization in Transfused Patients

Background: Alloimmunization to red blood cell (RBC) antigens is a clinically-significant problem, but the mechanisms underlying antibody induction remain poorly understood. Data from murine models has suggested that inflammation can promote blood group alloimmunization. To our knowledge, only one group (Ramsey & Smietana, Transfusion 1995;35:582) has examined the influence of inflammation on RBC alloimmunization; however, study subjects were predominantly female, making it difficult to determine the contribution of inflammation towards transfusion-related alloimmunization. Thus, the aim of our study was to examine whether inflammation associated with chronic autoimmune disorders increases the risk for development of transfusion-related RBC alloantibodies in a primarily male patient cohort.

Methods: The transfusion records of alloimmunized patients at a Veterans’ Affairs facility were extracted from a large database of individuals who underwent type and screen testing from 1961 through May, 2014. For alloimmunized patients, the following information was retrospectively collected: 1) demographic data including gender, 2) the number and specificity of alloantibodies reactive at 37°C and/or antihuman globulin phase, and 3) the presence of an underlying chronic inflammatory autoimmune disorder (and the specific diagnosis, as applicable). In addition, the records of 250 randomly-selected patients undergoing RBC administration were reviewed to establish the transfusion rate among individuals with chronic inflammatory autoimmune disorders.

Results: Among all patients undergoing type and screen testing at our facility, 220 had one or more detectable alloantibodies. Patients with a chronic inflammatory autoimmune disorder constituted nearly 16% (35/220) of total alloimmunized individuals. These patients formed 50 total alloantibodies (1.4 antibodies per alloimmunized patient). Anti-D (n=10) and anti-K (n=10) were the two most common alloantibodies detected in this group, followed by anti-E (n=8) and anti-C (n=6). Men represented about 86% (30/35) of alloimmunized patients with an autoimmune disorder, indicating that the vast majority of detected antibodies resulted from transfusion rather than pregnancy. The most common autoimmune disorder among alloimmunized patients was psoriasis (9/33; 27%), followed by rheumatoid arthritis (6/33; 18%). Examination of the charts of randomly-selected patients who underwent RBC transfusion showed that 8.4% (21/250) had an underlying chronic inflammatory disorder. The ratio of alloimmunized patients with an autoimmune disease to those without one was significantly different than the ratio of transfused patients with an autoimmune disease to those without one (P=0.012, chi square test; P=0.018, chi square test with Yates’ correction for continuity).

Conclusions: Patients with autoimmune diseases represented a substantial portion of individuals with transfusion-associated alloantibodies. Patients with chronic inflammatory disorders formed alloantibodies at nearly double the rate at which they were transfused. As such, precautionary interventions (e.g., extended phenotypic matching for K, E, and C antigens) may be warranted for patients with chronic inflammatory disorders.