Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis.

BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis. AIMS: To investigate the prevalence of CD among individuals with osteoporosis. METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression. RESULTS: We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI = 1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I2  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%). CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.

Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short-term cultures using good manufacturing practice-compliant reagents. This process uses CD40L-activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.