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Background Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD and account for 65% to 70% of cases in Western countries. Objective We sought to understand the clinical manifestations associated with the X-linked CGD carrier state. Methods We undertook a comprehensive retrospective study of 162 affected female subjects. We examined dihydrorhodamine 123 (DHR) oxidation data for percentage of X-chromosome inactivation. We correlated lyonization (%DHR + ) with clinical features. Where possible, we followed %DHR + values over time. Results Clinical data were available for 93 female subjects: %DHR + values were 46% (mean) and 47% (median; SD, 24). Using the %DHR + value as the criterion for X inactivation, 78% of patients had levels of inactivation of 20% to 80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR + values of 8% (n = 14; range, 0.06% to 48%), and those with only autoimmune or inflammatory manifestations had median %DHR + values of 39% (n = 31; range, 7.4% to 74%). Those with both infections and autoimmunity had low %DHR + values (n = 6; range, 3% to 14%). A %DHR + value of less than 10% was strongly associated with infections (odds ratio, 99). Strong association persisted when %DHR + values were less than 20% (odds ratio, 12). Autoimmunity was not associated with %DHR + values. In 2 sets of identical twins, the %DHR + populations tracked closely over time. Although the %DHR + populations were very similar between sisters, those between mothers and daughters were unrelated. Conclusions A low %DHR + value strongly predicts infection risk in X-linked CGD carriers, and the carrier state itself is associated with autoimmunity.

These essays may be seen as representing three main contemporary approaches to literature and medicine research: the educational, therapeutic and theoretical. Kabir Matharu’s piece discusses the applications of literary study in a medical education setting; Marilyn McIntyre’s piece shows the therapeutic value of poetry, and its unique ability to capture experiences of illness; and Masha Mimran’s piece uses literary criticism to interpret both medical and fictional texts. By grouping these three essays together, we hope to show the commonality and complementarity between research done by scholars in the Medical Humanities from disparate disciplinary backgrounds: all three attempt to break down the boundaries between medical diagnosis and lived human experience. One can best appreciate this project by keeping in mind the empathic process, which links the mind and body, intellect and emotion, creativity and interpretation.

Chronic Granulomatous Disease (CGD) is an inherited defect in superoxide production leading to life-threatening infections, granulomas, and, possibly, abnormal immunoglobulin concentrations. We investigated whether factors controlling antibody production, such as B-cell activating factor (BAFF), were altered in CGD. CGD subjects had significantly increased mean (2.3-fold, p < 0.0001) plasma concentrations of BAFF compared to healthy donors. Patients on IFN-γ treatment had significantly higher BAFF concentrations compared with CGD patients not taking IFN-γ (1.6-fold, p < 0.005). Leukocytes from CGD subjects produced normal amounts of BAFF in response to IFN-γ or G-CSF in vitro. Expression of BAFF-R and TACI was significantly reduced on CGD B cells. Elevated BAFF in CGD correlated with CRP (R = 0.44), ESR (R = 0.49), and IgM (R = 0.47) and increased rapidly in healthy subjects following intravenous endotoxin administration. These findings suggest that elevated BAFF in CGD subjects and healthy donors is a consequence of acute and chronic inflammation.