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Liver cirrhosis is associated with defective vaccine responses and increased infections. Dysregulated B cell compartments in cirrhotic patients have been noticed but not well characterized, especially in the spleen. Here, we comprehensively investigated B cell perturbations from the spleens and peripheral blood of cirrhotic patients. We found that liver cirrhosis significantly depleted both switched and nonswitched splenic memory B cells, which was further confirmed histologically. Bulk RNA-seq revealed significant metabolic defects as the potential mechanism for the impaired splenic B cell functions. Functionally, the splenic memory B cells from cirrhotic patients showed strong metabolic defects and reduced proliferation compared with those from healthy controls. Thus, liver cirrhosis extensively disturbs the splenic and peripheral B cell compartments, which may contribute to defective humoral immunity during liver cirrhosis.

e20513 Background: Patients with Multiple Myeloma (MM) are at risk for developing sepsis due to defective humoral immunity, underlying disease factors like renal failure, iron overload, and treatment with immunosuppressive agents. Sepsis is a significant cause of morbidity and mortality in patients with MM. In this study, we aimed to study trends of inpatient outcomes and health care burden of patients with sepsis in MM. Methods: Adult patients with MM admitted to the hospital from 2012 to 2017 were identified from the Nationwide Inpatient Sample database and were stratified into two groups based on the diagnosis of sepsis. Multivariate regression analysis was used to adjust for confounders when calculating for mortality. Statistical tests for trends of mortality, length of stay and hospital charges were performed. Results: A total of 513,615 patients with MM met the inclusion criteria. Sepsis was found to be the most common cause of admission amongst these patients (12.2%) and of the patients with MM who died in the hospital, 38.1% carried the primary diagnosis of sepsis. Mean age of the patients was 70.1 years and they were predominantly Caucasian (62.1%) with male preponderance (57.7%). MM patients admitted with sepsis were found to have higher mortality (15.7 and 3.5% P < 0.0001),higher hospital costs (22,082$ vs 15,206; P < 0.0001) and longer hospital stays (8.1 days vs 6.0 P < 0.0001) when compared to those admitted for other reasons. Temporal trends have been noted to improve over the years, with mortality decreasing from 18% to 13.1%, (p trend < 0.001). Length of stay (in days) decreased from 8.3 to 7.7 days (p trend = 0.009) and hospital charges (in dollars) decreased from 22,407 to 21,209 (p trend < 0.001). Conclusions: Although the improving trends are promising, sepsis still continues to be significantly contributing to morality and morbidity in patients with MM. Measures to identify the changing spectrum of infectious diseases, their predisposing risk factors along with strategies to recognize and prevent early stages of sepsis could have a significant impact on lowering mortality and health care burden. [Table: see text]

The spectrum of opportunistic infections seen in HIV disease in children resembles that in adults. Most striking, however, is the role of bacterial infections in pediatric AIDS. Although defective humoral immunity seems to play a significant role in predisposing to bacterial infections, there is no direct correlation between the risk for bacterial infections and poor B cell mitogenic responses or hypergammaglobulinemia (Rubinstein 85), suggesting additional predisposing factors.

Serum-immunoglobulin measurements in 11,000 hospital patients disclosed 24 propositi and 7 out of 15 of their relatives with idiopathic isolated γA deficiency. A review of these patients and published reports of other patients revealed that: (1) isolated γA deficiency has a prevalence of 1 in 500 and can be associated with ataxia telangiectasia; and (2) 69 of 75 patients had symptoms of recurrent sinopulmonary infection, or malabsorption, or thrombocytopenia, hypersplenism, and autoimmune syndromes. Evidence of defective humoral immunity with overcompensation of cellular immunity supports the hypothesis that immune imbalance can account for the symptomatology.