Study Design: Systematic review and meta-analysis. Objectives: Cervical spinal cord compression (SCC) due to degenerative changes of the spine is a frequent finding on magnetic resonance imaging (MRI). While most people remain asymptomatic, a proportion develop symptoms of degenerative cervical myelopathy (DCM). DCM is an often-progressive neurological disease that can cause quadriplegia. The epidemiology of SCC and DCM is poorly understood. We sought to estimate the prevalence of degenerative cervical SCC and DCM from cross-sectional cohorts undergoing MRI. Methods: We conducted a systematic review and meta-analysis of MRI reports on human subjects older than 16 years with degenerative SCC. A predetermined search strategy was used to identify relevant literature on MEDLINE. Title and abstract screenings were followed by full text screening. Data was extracted and analyzed by fixed or random-effects models. Results: The present search returned 1506 publications. Following our exclusion criteria, 19 studies were included. Subgroup analysis of 3786 individuals estimated the prevalence of asymptomatic SCC in a healthy population as 24.2% with a significantly higher prevalence of SCC in older populations compared with younger populations and American/European populations compared with Asian populations. Subgroup analysis of 1202 individuals estimated the prevalence of DCM in a healthy population as 2.3%. Conclusions: We present the first estimates of the prevalence of asymptomatic SCC and DCM. Studies investigating the epidemiology of SCC are heterogeneous in methodology and results. These data indicate the need for more studies into the epidemiology of SCC and DCM performed with consistent methodologies.

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Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg.