Circadian rhythm of oestradiol: Impact on the bone metabolism of adult males

Background: Few studies have examined the variation in oestradiol with respect to age and circadian rhythm and the subsequent effects on BMD. Aim: Demonstrate the presence or absence of a circadian rhythm for oestrodial in older men and the integral role of concerted circadian rhythms of several factors including parathyroid hormone (PTH) in regulating biochemical markers of bone resorption and formation. Examine whether concentrations of both circulating total and bioavailable oestrogen in men differ with age and BMD. Design: Males were recruited: young men with normal BMD, older men with normal BMD and older men with osteoporosis. Methods: Subjects were hospitalized for a 25-hour period. Blood samples were obtained every 30 minutes. Hormone analysis results were plotted and reviewed. Results: Both total and bioavailable oestradiol concentrations were significantly lower in the older men than the young men (Total oestradiol: 34.5±4.4 pmol/L vs. 49.0±6.5 pmol/L, p<0.0001; Bioavailable oestradiol 16.7±2.2 pmol/L vs. 26.3±3.6 pmol/L, p<0.0001). Bioavailable oestrogen rhythm mirrored that of total estrogen. Conclusion: Both age groups with normal BMD display circadian rhythmicity with respect to circulating and bioavailable oestradiol. Younger men have increased mean total and bioavailable oestrogen concentrations and later acrophase compared to older counterparts. In older men with low BMD, total circulating oestrogen was not significantly different compared to age-matched older men with normal BMD; bioavailable oestrogen was significantly lower. Total oestrogen demonstrated a concerted circadian rhythm in all 3 groups, but bioavailable oestrogen did not demonstrate circadian rhythmicity in older men with decreased BMD

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases

OBJECTIVES: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. // METHODS: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. // RESULTS: Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82–100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. // CONCLUSION: These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia

Immunoglobulin abnormalities are frequent in patients with lupus nephritis

Hypogammaglobulinemia is a complication of B-cell targeting therapies (BCTT), used in vasculitis, rheumatoid arthritis and systemic lupus erythematosus (SLE). Since autoimmune diseases are associated with underlying and induced immune abnormalities, several societies recommend assessing immune function before and during rituximab treatment. In SLE, polyclonal hypergammaglobulinemia is the typical alteration of gammaglobulins, though hypogammaglobulinemia has also been reported. This is a cross-sectional study describing immunoglobulin levels measured as part of routine care in patients with lupus nephritis, a group with multiple factors contributing to immunoglobulin abnormalities, including immune dysregulation, immunosuppression and nephrotic syndrome. Polyclonal hypergammaglobulinemia occurred in 15/83 (18.1%) patients. In contrast, low levels of immunoglobulins were found as follows: selective IgA deficiency 2/83 (2.4%), reduced IgG levels 7/83 (8.4%), reduced IgM 14/83 (16.9%). Only 1 patient required immunoglobulin replacement. Immunoglobulin abnormalities are frequently found in lupus nephritis, ranging from polyclonal hypergammaglobulinemia to hypogammglobulinemia. Consequently, immunoglobulin levels should be assessed prior to commencing BCTT.Other Information Published in: BMC Rheumatology License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s41927-019-0079-2</p