Objective: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never‐treated, recent‐onset psoriatic arthritis (PsA).Methods: High‐throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids.Results: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis.Conclusion: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis–PsA pathogenesis and the associated immune response merits further study.

Objective: To profile the abundance and diversity of subgingival oral microbiota in patients with never‐treated, new‐onset rheumatoid arthritis (RA).Methods: Periodontal disease (PD) status, clinical activity, and sociodemographic factors were determined in patients with new‐onset RA, patients with chronic RA, and healthy subjects. Multiplexed‐454 pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between the presence/abundance of bacteria and disease phenotypes. Anti–Porphyromonas gingivalis antibody testing was performed to assess prior exposure to the bacterial pathogen P gingivalis.Results: The more advanced forms of periodontitis were already present at disease onset in patients with new‐onset RA. The subgingival microbiota observed in patients with new‐onset RA was distinct from that found in healthy controls. In most cases, however, these microbial differences could be attributed to the severity of PD and were not inherent to RA. The presence and abundance of P gingivalis were also directly associated with the severity of PD and were not unique to RA. The presence of P gingivalis was not correlated with anti–citrullinated protein antibody (ACPA) titers. Overall exposure to P gingivalis was similar between patients with new‐onset RA and controls, observed in 78% of patients and 83% of controls. The presence and abundance of Anaeroglobus geminatus correlated with the presence of ACPAs/rheumatoid factor. Prevotella and Leptotrichia species were the only characteristic taxa observed in patients with new‐onset RA irrespective of PD status.Conclusion: Patients with new‐onset RA exhibited a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota profile in patients with new‐onset RA was similar to that in patients with chronic RA and healthy subjects whose PD was of comparable severity. Although colonization with P gingivalis correlated with the severity of PD, overall exposure to P gingivalis was similar among the groups. The role of A geminatus and Prevotella/Leptotrichia species in this process merits further study.

Osteoarthritis is often a progressive and disabling disease, which occurs in the setting of a variety of risk factors – such as advancing age, obesity, and trauma – that conspire to incite a cascade of pathophysiologic events within joint tissues. An important emerging theme in osteoarthritis is a broadening of focus from a disease of cartilage to one of the 'whole joint'. The synovium, bone, and cartilage are each involved in pathologic processes that lead to progressive joint degeneration. Additional themes that have emerged over the past decade are novel mechanisms of cartilage degradation and repair, the relationship between biomechanics and biochemical pathways, the importance of inflammation, and the role played by genetics. In this review we summarize current scientific understanding of osteoarthritis and examine the pathobiologic mechanisms that contribute to progressive disease.

Yin-Yang T Cell Signaling: Immune responses are kept in check by CD4 ⁺ regulatory T cells (T _reg ) that suppress other immune cells, including CD4 ⁺ effector T cells (T _eff ). T _reg and T _eff cells have many signaling components in common, yet triggering through their T cell receptors (TCRs) leads to very different outcomes. Zanin-Zhorov et al. (p. 372 , published online 25 March) compared the recruitment of signaling molecules to the immunological synapse after TCR triggering in T _reg and T _eff cells. Although T _reg cells do form synapses, signaling molecules that promote T _eff activation, such as protein kinase C-θ (PKC-θ), were not recruited. Inhibition or depletion of PKC-θ in T _reg cells led to suppressive activity against T _eff cells, whereas costimulation enhanced PKC-θ recruitment and less suppression. Together, this suggests that PKC-θ is inflammatory in both T _reg and T _eff cells; however, by excluding it from the synapse, T _reg cells are able to maintain suppression in the face of TCR signaling.

Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript will summarise emerging observations from cell biology, preclinical and preliminary clinical trials that elucidate interactions between the bone and cartilage components in particular. Bone and cartilage health are tightly associated. Ample evidence has been found for bone changes during progression of OA including, but not limited to, increased turnover in the subchondral bone, undermineralisation of the trabecular structure, osteophyte formation, bone marrow lesions and sclerosis of the subchondral plate. Meanwhile, a range of investigations has shown positive effects on cartilage health when bone resorption is suppressed, or deterioration of the cartilage when resorption is increased. Known bone therapies, namely oestrogens, selective oestrogen receptor modifiers (SERMs), bisphosphonates, strontium ranelate, calcitonin and parathyroid hormone, might prove useful for treating two critical tissue components of the OA joint, the bone and the cartilage. An optimal treatment for OA likely targets at least these two tissue components. The patient subgroups for whom these therapies are most appropriate have yet to be fully defined but would likely include, at a minimum, those with high bone turnover.