Faculty Bibliography

OBJECTIVE:Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy. METHODS:We generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level. RESULTS:T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant - a strong genetic susceptibility marker for human systemic lupus erythematosus - also down-modulated the secretion of Th17-skewing cytokines. CONCLUSION/CONCLUSIONS:Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders.

A 46-year-old Hispanic man presented with fever, genital ulcers, left eye redness and chest pain. Physical examination was notable for a healed oral ulcer and scrotal ulcers, and bilateral superficial thrombophlebitis. He was found to have new-onset pancytopenia. CT of the chest showed pericardial and pleural effusions and rapidly progressing inflammation of the aortic arch and ascending vessels. Although the patient had Behcet's disease (BD)-like symptoms, pancytopenia could not be explained by the diagnosis, prompting a bone marrow biopsy which showed myelodysplastic syndrome. This report highlights the importance of excluding alternate disorders before making a diagnosis of Behcet's disease if atypical, BD-incompatible or incomplete constellations of symptoms and findings are present.

A 40-year-old Chinese man was admitted for haemoptysis and progressive deep vein thrombosis involving the inferior vena cava (IVC) despite anticoagulation. An IVC filter had been placed earlier at an outside hospital. CT angiography revealed two pulmonary artery aneurysms. The patient was found to have a history of oral and genital ulcers, uveitis and erythema nodosum, thus meeting criteria for Behcet's disease. Other causes of the haemoptysis and thrombophilia were excluded. He underwent successful coil embolisation of the pulmonary artery aneurysms and responded well to immunosuppressive therapy with cyclophosphamide and steroids. Anticoagulation was cautiously continued to limit the long-term risk of secondary thrombosis from his IVC filter. The patient remains well 5 months after initiation of immunosuppressive therapy. Making a diagnosis of Behcet's disease in the setting of thrombosis is crucial, as treatment must include immunosuppression, and, thus, fundamentally differs from the management of most other thrombotic disorders.

Headaches are a common, but under-recognized and understudied symptom in the context of the rheumatic diseases. They can result from intracranial pathology, such as parenchymal and meningeal inflammation, thrombosis, space-occupying lesions, and more. Inflammation, irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses can equally cause headaches. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, and generally require only symptomatic relief, the former type of headaches may signal disease manifestation, progression, or complication. Thus, familiarity with common and uncommon headache syndromes related to rheumatologic disorders as well as with their possible underlying disease processes and mechanisms is important. This will help to successfully develop an effective approach toward the evaluation of patients presenting with headaches in a rheumatologic context, and, ultimately, diagnose and treat potentially severe underlying disease.

OBJECTIVE: The aim of the study is to determine the frequency and functionality of blood conventional dendritic cells (cDCs) in relation to disease activity in systemic lupus erythematosus. METHODS: Blood cDCs were enumerated for 34 SLE patients, defined as "active" (SLEDAI>/=4) or "inactive" (SLEDAI<4), 26 RA subjects and 8 healthy subjects by FACS. cDC activation was measured by IL-12p40/70 staining following resiquimod stimulation. RESULTS: The frequency of blood cDCs was significantly lower in active compared to inactive patients, however, with comparable cDC functionality. CONCLUSION: cDC frequency in active SLE is decreased with no perturbation in cDC function, possibly due to enhanced turnover and/or tissue-specific migration.