Mapping and predicting mortality from systemic sclerosis.

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.

Plasma cells are not restricted to the CD27+ phenotype: characterization of CD27-CD43+ antibody-secreting cells.

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders. Conclusion: we characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.

Connective tissue disease associated interstitial pneumonia: a challenge for both rheumatologists and pulmonologists.

Interstitial lung disease (ILD) can be either idiopathic, the result of exposure or may be associated with extrapulmonary diseases. Among the latter, connective tissue diseases (CTDs) make up the largest part. The identification, follow-up and treatment of CTD-associated ILD (CTD-ILD) are a challenge for every physician as ILD can occur before, during and after the diagnosis of CTD. Early detection of pulmonary involvement is an essential task for the treating rheumatologist and recognition of the underlying CTD can pose a challenge for the treating pulmonologist. Multidisciplinary engagement towards the patient is therefore indispensable for optimal clinical care. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 326-335).