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Somatostatin and its analogues are known to have modulatory effects on immune response and their anti-proliferative, anti-angiogenic, and analgesic properties make them attractive candidates for a therapeutic use in immune-mediated diseases, such as rheumatoid arthritis. Here, we demonstrate the ability of the somatostatin analogue octreotide to inhibit interleukin-15 and to increase interleukin-10 production by rheumatoid arthritis fibroblast-like synovial cells maintained in a chronic inflammatory state. We also prove that the inhibitory effect of octreotide on interleukin-15 and tumor necrosis factor-α production depended on the increase in interleukin-10, since neutralizing anti-interleukin-10 antibody was able to partially reverse this inhibition. In addition, our observations suggest an octreotide control on purinergic signaling, with an inhibitory effect on purinergic P2X and P2Y receptors activation. This would have great implications, considering the roles of P2 receptors in the onset of inflammation. Data here reported extend knowledge on the biological action of octreotide and underline its multiple effects on immune response, which could make octreotide an attractive and valid support for the therapy of diseases where several inflammatory mediators are involved, such as rheumatoid arthritis, and in which the simultaneous action on different aspects can be a successful strategy.

Cardiovascular (CV) comorbidities are a frequent extra-articular manifestation of rheumatoid arthritis (RA). Cardiovascular disease (CVD) with accelerated atherosclerosis is a major cause of morbidity and mortality in patients with RA. Subclinical CVD may be present since the early phase of RA. Not only traditional but also non-traditional CV risk factors are involved in the pathogenesis of RA-related CVD. Due to the lack of specifically designed randomized clinical trials, it is still unclear which tools to use to perform CV risk assessment, how to interpret the results and which interventions are appropriate in RA patients both to prevent and to manage CVD. Based on the available evidence, we propose a practical approach.

Objective: To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations. Materials and methods: Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24–85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient. Results: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p

Despite its infrequent occurrence, the possible development of lymphoma or lymphoid lung disease in patients with Sjögren's syndrome should always be borne in mind. We describe a case of bronchus-associated lymphoid tissue (BALT) lymphoma in a patient with Sjögren's syndrome that clearly exemplifies the wide-ranging problems of diagnosing, treating and following such patients. This difficulty is due to the fact that the clinical and radiological findings suggest interstitial lung disease, and histological assays are required for a correct diagnosis. A precise knowledge of the various histological and radiological patterns of lung involvement can aid patient management.

Bilateral vocal fold immobility (BVFI) can be the result of a primary disorder or as an iatrogenic complication of surgery or intubation. Laryngeal involvement can be a rare complication of connective tissue disorders and it usually occurs in association with other symptoms and signs that indicate active disease. We present a case of BVFI in a patient with an overlap syndrome rheumatoid arthritis/systemic sclerosis, referred to our division because of dysphonia and dyspnea. The video-laryngostroboscopy showed the presence of BVFI. Physical examination, blood tests, lung and neck high resolution computed tomography scans did not demonstrate significant abnormalities. She was treated with pulses of intravenous methylprednisolone with slow improvement.

We thank Dr. Verdelli and colleagues for their comments regarding our case report of the potential safe role of tocilizumab monotherapy in the treatment of a patient with rheumatoid arthritis (RA) and iatrogenic Kaposi sarcoma (KS) [1]. In the case reported by Dr. Verdelli and colleagues [2], KS arose under a treatment regimen of tocilizumab monotherapy. The two patients’ characteristics are quite different. Our patient already had KS before tocilizumab, and he was naive from potent immunosuppressants other than methotrexate [1]. By contrast, the other patient [2] developed ‘ex novo’ KS after receiving several immunosuppressants, traditional and biologic disease-modifying antirheumatic drugs before receiving tocilizumab, thus probably resulting in a more severe suppression of immune system response. Moreover, the patient described in this second report [2] is older (78 years old), and also developed psoriasis, suggesting a complex immune dysregulation. It must be stressed that no relapse of KS was noted in our patient with RA treated with tocilizumab [1], although we cannot exclude that the natural history of KS in our patient would imply a remission of the tumor, independently from antirheumatic therapies. In our report [1], a key feature is the sustained remission of RA. The disease was severe in our case, and we had no further therapeutic options available apart from tocilizumab. Although no evidence exists for the safety of tocilizumab therapy in KS, there is a strong theoretical rationale for this treatment [3]. In fact, no relapse of KS was observed, and this is a very positive finding and an interesting solution to the conundrum the patient presented with. In our opinion, this is a very intriguing topic, and as our understanding of the potential therapeutic targets increases, so too do the treatment options. There is considerable interest in expanding knowledge and clinical applications of tocilizumab; however, there are no published studies on KS. Although ours are the only two anecdotal cases reported, they may pave the way to further prospective studies.

SDF-1 (CXCL12), a CXC chemokine, has a primary role in signalling the recruitment of haematopoietic stem-cell precursors to the bone marrow during embryonic development. In post-natal life, SDF-1 is widely expressed and is induced in chronically inflamed tissues such as psoriatic skin and the rheumatoid synovium, but has also been implicated in the migration of lymphocytes to lymphoid organs. To investigate the role of SDF-1 in recirculation and homing in vivo we have developed a model in which human peripheral lymph nodes (huPLN) are transplanted into SCID mice. We have shown that huPLN transplants are viable and are vascularised by the murine circulation, forming functional anastomoses with transplant vessels. In addition grafts retain some of the histological features of the pretransplantation tissue, such as follicular dendritic cell-associated B-cell aggregates, lymphatic and HEV markers. We also show that SDF-1 is capable of inducing the migration of an SDF-1 responsive cell-line (U-937) and human PBL's from the murine circulation into the grafts in a dose dependant manner which is inhibitable by CXCR4 blockade. The mechanism of action of SDF-1 in this model is independent from that of TNF-α and does not rely on the upregulation of adhesion molecules (such as ICAM-1) on the graft vascular endothelium. This is the first description of huPLN transplantation into SCID mice, and of the functional effects of SDF-1 regarding the migration of human cells into huPLN in vivo. This model provides a powerful tool to investigate the pathways involved in cell-migration into lymphoid organs and potentially to target them for therapeutic purposes.