Phenotypic and functional characteristics of murine CD11c+ B cells which is suppressed by metformin.

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs.

Association of Hydroxychloroquine use and Hemolytic Anemia in Patients With Low Levels of Glucose-6-Phosphate Dehydrogenase.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is linked to hemolytic anemia with certain medications and is the most common enzyme deficiency worldwide. Although the American College of Rheumatology does not recommend routine testing for G6PD prior to initiation of hydroxychloroquine (HCQ), the package insert for HCQ does recommend careful use in patients with G6PD deficiency. METHODS: We identified eligible subjects seen at our tertiary care, urban medical center between 1997 and 2018. Case records were analyzed for G6PD deficiency, HCQ use, length of exposure to HCQ, demographic characteristics, and laboratory evidence of hemolysis. RESULTS: We found 5264 patients who were prescribed HCQ, of which 49.5% (2605 patients) were screened for G6PD deficiency. Of the screened patients, 36 were found to be G6PD-deficient. Of the G6PD-deficient patients, 18 were exposed to HCQ. No evidence of hemolysis was found in these exposed patients. CONCLUSIONS: Despite more than 500 months of cumulative exposure time to HCQ, there were no cases of hemolysis. These findings are in line with recently published data and suggest that this interaction is not associated with clinically significant hemolysis in our population of mainly African American and Hispanic patients. Limitations to our study are potential bias due to case review design and lack of prior assessment of episodes of hemolysis before HCQ exposure. A high proportion of our patients were Hispanic, suggesting no increase of adverse events in this subgroup. A larger longitudinal trial would be needed to definitively answer the question of the safety of HCQ in G6PD-deficient patients.