Anti-transcription intermediary factor 1-gamma IgG2 isotype is associated with cancer in adult dermatomyositis: an ENMC multinational study.

OBJECTIVE: To assess the role of the anti-TIF1γ auto-antibody (aAb) IgG2 isotype as a biomarker of cancer in anti-TIF1γ aAb-positive adult DM. METHODS: International multicentre retrospective study with the following inclusion criteria: (i) diagnosis of DM according to ENMC criteria; (ii) presence of anti-TIF1γ IgG aAb determined using an in-house addressable laser bead immunoassay (ALBIA) from cryopreserved serums sampled at time of DM diagnosis and (iii) available baseline characteristics and follow-up data until the occurrence of cancer and/or a minimum follow-up of 1 year for patients without known cancer at diagnosis. Detection and quantification of anti-TIF1γ IgG2 aAb was done using the in-house ALBIA. In addition, a recent ELISA commercial kit was used for anti-TIF1γ IgG aAb quantification. RESULTS: A total of 132 patients (mean age 55±15 years) of whom 72 (54.5%) had an associated cancer were analysed. The association between the presence of cancer and the presence of anti-TIF1γ IgG2 aAb was statistically significant (P = 0.026), with an OR of 2.26 (95% CI: 1.10, 4.76). Patients with cancer displayed significantly higher anti-TIF1γ IgG2 aAb ALBIA values with a median value of 1.15 AU/ml (IQR: 0.14-9.76) compared with 0.50 AU/ml (IQR: 0.14-1.46) for patients without cancer (P = 0.042). In addition, patients with cancer displayed significantly higher anti-TIF1γ IgG aAb ELISA values with a median value of 127.5 AU/ml (IQR: 81.5-139.6) compared with 93.0 AU/ml (IQR: 54.0-132.9) for patients without cancer (P = 0.004). CONCLUSION: These results suggest considering anti-TIF1γ IgG2 ALBIA and IgG ELISA values as biomarkers of cancer in anti-TIF1 γ aAb-positive adult DM.

Role of Adaptive Immunity in the Development and Progression of Heart Failure: New Evidence.

Heart failure (HF) is considered the endpoint of a variety of cardiac diseases, which are the leading cause of death in adults and considered a growing pandemic worldwide. Independent of the initial form of cardiac injury, there is evidence linking the involvement of the immune system. In HF there is evidence of the participation of TH1, and TH17 cells, which account for sustained pathological chronic inflammation, cell migration, and the induction of specific pathological phenotypes of mononuclear cells. Of equal or even higher relevance are the B lymphocyte activation mechanisms that include production of pro-inflammatory cytokines, chemokines, and cardiac autoantibodies with or without activation of the complement proteins. Both of these unbalanced T- and B-cell pathways of the adaptive immune system are associated with cardiomyocyte death and tissue remodeling by fibrosis leading to a dysfunctional heart. At this time, therapy with neutralizing antibodies and the use of anti-cytokine immunomodulators to counteract the immune system effects have reached a plateau of mixed results in clinical trials. Nevertheless, recent evidence showed promising results in animal models that suggest that modulation of the adaptive immune system cells more than some of their effector molecules could have benefits in HF patients. This review summarizes the role of the adaptive immunity cells in HF, considering the sustained activation of adaptive immune system as a potential contributor to disease progression in humans and experimental models where its regulation provides a new therapeutic target.