Increased T Cell Plasticity With Dysregulation of Follicular Helper T, Peripheral Helper T, and Treg Cell Responses in Children With Juvenile Idiopathic Arthritis and Down Syndrome-Associated Arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common inflammatory arthritis in children; however, an aggressive, erosive arthritis of little-known immunologic mechanism occurs 20 times more frequently in children with Down syndrome. This study was undertaken to characterize T cell and B cell polyreactivity, follicular helper T (Tfh) cell, peripheral helper T (Tph) cell, and Treg cell responses, and synovial inflammation in Down syndrome-associated arthritis (DA). METHODS: Multiparametric flow cytometric analysis and Simplified Presentation of Incredibly Complex Evaluations (SPICE) software were used to examine peripheral blood B cell populations and T cell cytokine responses in patients with DA, JIA, Down syndrome (trisomy 21 [T21]), and in healthy controls. Tfh and Tph cell frequency and origin, in addition to Treg cell frequency, were also evaluated. Synovial inflammation was assessed by immunohistology. RESULTS: Expansion of IgM-only memory B cells was demonstrated in DA compared to JIA (mean ± SEM 22.48 ± 3.278 versus 9.011 ± 1.317; P = 0.005), paralleled by decreased frequency of transitional B cells. T cell responses in DA were characterized by marked functional plasticity, as was evident from the increased frequency of polyfunctional CD8+ Th cells (P < 0.05), CD161+ Th cells (P < 0.05), and CD8- Th cells (P < 0.001), and positivity for tumor necrosis factor, interferon-γ, interleukin-17A, or granulocyte-macrophage colony-stimulating factor, compared to all other groups. Significant expansion of CXCR3+CCR6+ (Th1/Th17) Tfh cells (P = 0.003) and CXCR3+CCR6+ Tph cells (P = 0.01), paralleled by a decrease in CXCR3-CCR6- (Th2) Tfh cells was observed in DA compared to T21. Treg cells were significantly reduced in DA compared to T21 (mean ± SEM 7.111 ± 0.9518 versus 11.96 ± 1.055 versus; P = 0.0028), with a specific reduction in the naive:memory Treg cell ratio. Marked synovial tissue inflammation and increased T cell and B cell infiltrations were demonstrated in DA compared to JIA. CONCLUSION: DA is more common and more aggressive than JIA. It is characterized by increased polyreactive Th, Tfh, and Tph cell responses, reduced Treg cell frequency, and evidence of increased synovial inflammation, all of which are potentially distinct from JIA and T21.

Shrinking lung syndrome and systemic lupus erythematosus: a case series and literature review.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus, characterized by progressive dsypnoea, reduced lung volumes and associated restrictive lung physiology. Here, we provide two previously unreported cases, and review the available literature on the pathophysiology, clinical features and management of SLS. Effective treatment can prevent further deterioration or lead to improvement in abnormal lung function. A heightened awareness of SLS and its management is therefore required to prevent disease progression and increased morbidity.

Pulmonary cystic hydatid disease in Ireland.

BACKGROUND: Hydatid disease is rare in Ireland and its incidence and prevalence are unknown. Most cases are diagnosed by a combination of clinical findings, morphological features on imaging and by serological testing. AIMS: We describe an Irish case of pulmonary hydatid disease detected at bronchoscopy by bronchoalveolar lavage, and discuss the diagnosis and treatment of the disorder. CONCLUSION: The diagnosis of this rare disease requires a high index of suspicion. Treatment is primarily surgical, with a role for antihelminthic agents.

Disease-modifying anti-rheumatic drug therapy and structural damage in early rheumatoid arthritis.

The appearance of measurable structural damage in rheumatoid arthritis (RA) is an indicator of disease severity and future disability. Disease-modifying anti-rheumatic drugs (DMARDs) used in combination appear to be more effective than monotherapies at reducing the rate of progressive joint damage during randomized controlled trials. In clinical practice, however, combination DMARD therapy is still largely reserved for patients who have failed to respond to monotherapy. High dose corticosteroid, when given in early disease with combination DMARD therapy, may continue to ameliorate disease severity and progression for years after discontinuation of the high dose. To date, no DMARD combination has totally arrested joint damage in all patients with early RA. Future randomised controlled trials should always include prospective radiographic data as a primary outcome measure.