Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease-associated antisynthetase syndrome (AS-ILD) carries significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are the mainstay of treatment. Human immunoglobulin (IVIg), an immunomodulator without immunosuppressive properties, is effective in myositis but the evidence supporting its use in ILD is scarce. OBJECTIVE: To describe clinical outcomes of AS-ILD patients receiving IVIg. METHODS: Retrospective analysis of AS-ILD patients. Linear mixed models using restricted maximum likelihood estimation was used to estimate the change in lung function and corticosteroid dose over time. RESULTS: Data from 17 patients was analyzed. Median follow-up was 24.6 months. Fourteen patients had refractory disease. The mean percent-predicted forced vital capacity (FVC%) (p = 0.048) and percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (p = 0.0223) increased over time, while the mean prednisone dose (p < 0.001) decreased over time. Seven patients achieved a >10% increase in FVC%, including two who used IVIg as initial treatment. Five patients showed a >10% increase in DLCO% and TLC%. Nine (53%) patients experienced side effects. CONCLUSIONS: IVIg may be a useful complementary therapy in active progressive AS-ILD but is associated with potential side effects. Fssssurther investigation is required to determine the value of IVIg as an initial treatment in AS-ILD.

mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis.

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.

Revisiting thalidomide: fighting with caution against idiopathic pulmonary fibrosis.

Thalidomide is an infamous drug whose use by pregnant women in the middle of last century tragically resulted in serious birth defects. However, as a result of its potent immunomodulatory, anti-inflammatory and antiangiogenic properties, thalidomide may be a potential therapy in many diseases. In recent years, thalidomide has been used effectively to treat various malignancies, including multiple myeloma, myelodysplastic syndromes, renal cell cancer, glioblastoma multiforme and prostate cancer. In addition, thalidomide has also proven effective against other immune-related diseases, including erythema nodosum leprosum and sarcoidosis. Idiopathic pulmonary fibrosis (IPF) is a deadly fibrotic disease with no effective treatment options. However, there is data to suggest that thalidomide may be useful in treating the chronic, disabling cough that accompanies IPF. It remains to be seen whether the immunomodulatory and antiangiogenic properties of thalidomide will also make it a potential therapy against the clinical progression of IPF.