Publications

B-1a cells are a unique population of innate-like B cells with a highly restricted and self-reactive BCR repertoire. Preimmune "natural" IgM produced by B-1a-derived plasma cells is essential for homeostatic clearance of cellular debris and forms a primary layer of protection against infection. In this study, we take advantage of a fluorescent reporter of BCR signaling to show that expression of the orphan nuclear hormone receptor Nur77 is upregulated under steady-state conditions in self-reactive B-1a cells in response to chronic Ag stimulation. Nur77-deficient mice exhibit elevated natural serum IgM (but not IgG) and marked expansion of IgM plasma cells of B-1a origin. Moreover, we show that Nur77 restrains the turnover of B-1a cells and the accumulation of immature IgM plasma cells. Thus, we identify a new critical negative-regulatory pathway that serves to maintain B-1a cells in a quiescent state in the face of chronic endogenous Ag stimulation.

Neurologic manifestations are common in patients with antiphospholipid antibodies and include stroke, seizures, dementia, cognitive dysfunction, chorea, migraine, psychosis, and demyelinating disease. Many of these disorders mimic their idiopathic counterparts, yet treatment for antiphospholipid antibody-associated disease can be quite different compared with treatment of CNS disease not associated with these antibodies. For patients with antiphospholipid antibody-associated neurologic disease, anticoagulation or immunosuppressive therapy or both may significantly improve their symptoms. Thus, one should have a high index of suspicion for antiphospholipid syndrome in the appropriate clinical context.

Central nervous system (CNS) disease is an uncommon but significant complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and affects 3 primary areas of the CNS: the pituitary, the pachymeninges, and the CNS vasculature. Pituitary disease in uncommon, but hormonal deficiencies can be long lasting even in the face of excellent disease response. Chronic hypertrophic pachymeninigitis occurs in anti-proteinase 3-positive patients with systemic GPA and in anti-myeloperoxidase-positive patients with a milder and more limited form of the disease. Cerebral and spinal vasculitis due to GPA and MPA presents with focal and general neurologic abnormalities.

The gastrointestinal (GI) tract harbors most of the body's immune cells and is also a major HIV reservoir in ART-treated patients. To achieve a cure, most HIV-infected cells must be identified and eliminated. While obtaining gut biopsies is a relatively noninvasive method of sampling relevant tissue for monitoring HIV activity, immune cell isolation from these limited tissue samples has proven to be challenging. Enzymatic tissue digestion is required for maximal immune cell isolation from gut biopsies. However, these enzymatic digestions can also be detrimental for preservation of cellular surface markers that are required for accurate identification of various subsets of leukocytes. In this study, we describe an optimized protocol for isolation of lymphocytes from human gut biopsies. We also discuss our validation results, which show that compared with several other collagenase preparations, the use of CSLPA maintains high lymphocyte recovery while preserving the integrity of most cellular surface antigens that we tested. Importantly, chemokine receptors that are used to characterize various subsets of T cells, which are notorious for being digested during a typical enzymatic tissue digestion, are highly preserved using this protocol.

BACKGROUND

Severe mental illness (SMI) is associated with increased risk for type 2 diabetes, partly due to adverse metabolic effects of antipsychotic medications. In public health care settings, annual screening rates are 30%. We measured adherence to national diabetes screening guidelines for patients taking antipsychotic medications.

OBJECTIVE

To estimate diabetes screening prevalence among patients with SMI within an integrated health care system, and to assess characteristics associated with lack of screening.

DESIGN

Retrospective cohort study.

PARTICIPANTS

Antipsychotic-treated adults with SMI. We excluded participants with known diabetes.

MAIN MEASURES

Primary outcome was screening via fasting glucose test or hemoglobin A1c during a 1-year period.

KEY RESULTS

In 2014, 16,754 patients with SMI diagnoses were receiving antipsychotics. Seventy-four percent of these patients' providers ordered diabetes screening tests that year, but only 55% (9247/16,754) received screening. When the observation time frame was extended to 2 years, 73% (12,250/16,754) were screened. Adjusting for sex and race/ethnicity, young adults (aged 18-29 years) were less likely to receive screening than older age groups [adjusted RR (aRR) 1.23-1.57, p < 0.0001]. Compared to whites, screening was more common for Asians (aRR 1.141, 95% CI 1.089-1.195, p < 0.0001), less common for blacks (aRR 0.946, 95% CI 0.898-0.997, p < 0.0375), and no different for Hispanics (aRR 1.030, 95% CI 0.988-1.074, p = 0.165). Smokers were less likely to be screened than non-smokers (aRR 0.93, 95% CI 0.89-0.97, p < 0.0008). Utilization of either mental health or primary care services increased the likelihood of screening.

CONCLUSIONS

While almost three-fourths of adults with SMI taking antipsychotic medications received a lab order for diabetes screening, only 55% received screening within a 12-month period. Young adults and smokers were less likely to be screened, despite their disproportionate metabolic risk. Future studies should assess the barriers and facilitators with regard to diabetes screening in this vulnerable population at the patient, provider, and system levels.